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Review

“Cow’s Hoof” (Bauhinia L., Leguminosae): A Review on Pharmacological Properties of Austral South American Species

by
Renée Hersilia Fortunato
1 and
María Jimena Nores
2,*
1
Instituto de Botánica Darwinion (CONICET/ANCEFN), Labardén 200, Acassuso 1641, Argentina
2
Facultad de Ciencias Exactas, Físicas y Naturales, Instituto Multidisciplinario de Biología Vegetal (CONICET—Universidad Nacional de Córdoba), UNC, Vélez Sarsfield 1611, Argentina
*
Author to whom correspondence should be addressed.
Plants 2023, 12(1), 31; https://doi.org/10.3390/plants12010031
Submission received: 31 October 2022 / Revised: 17 November 2022 / Accepted: 21 November 2022 / Published: 21 December 2022
(This article belongs to the Collection Feature Review Papers in Phytochemistry)
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Abstract

:
The genus Bauhinia s.l. (Leguminosae), known as cow’s hoof, unha de boi or pata de vaca, has been used in traditional medicine worldwide. The aim of the present review is to summarize the studies published on the biological activity of the main native medicinal species reported in austral South America. Of the 14 species present in the region, 10 are consumed as leaf infusions to regulate glucose and lipid metabolism, as well as used for their anti-inflammatory and analgesic effects and to treat various diseases. Pharmacological properties have been recorded in seven species. Antioxidant, anticoagulant, antihypertensive, diuretic, antimicrobial and antitumor properties have been reported in B. forficata. Together with B. holophylla, they are important for their antidiabetic properties, since several studies indicate their effectiveness as a hypoglycemic agent. B. bauhinioides is distinguished for its anti-inflammatory and antithrombotic activities and S. microstachya for its analgesic properties. Anti-ulcer and wound healing activities recorded in B. holophylla and B. ungulata, respectively, are of particular interest. Most of the species possess antitumor activity. The antioxidant capacity of flavonoids and other bioactive compounds make these plants good candidates to assist or treat various alterations related with oxidative stress, such as diabetic complications. Thus, these species constitute promising targets for new bioactive substance research and phytotherapy.

Graphical Abstract

1. Introduction

The species of the genus Bauhinia s.l. (Leguminosae, Cercidoideae), popularly known as cow’s hoof, cow’s paw, orchid trees, pata de vacca, unha de boi, falsa caoba, pezuña de vaca or pata de vaca, have been traditionally employed by different communities all over the world for medicinal purposes. Bilobed or bifoliolate leaves are consumed in infusions to treat diabetes mellitus, pains, inflammation and several diseases. The genus has promising medicinal potential, since experimental studies have provided evidence of its therapeutic properties [1,2,3].
In austral South America, 14 native species of trees, lianas and shrubs inhabit forests of Argentina, Paraguay, Uruguay and the southern states of Brazil [4,5,6]. In the region, 10 of these species are popularly used mainly to regulate glucose and lipid metabolism, but also as anti-inflammatory and analgesic agents and for treating digestive, kidney and urinary disorders, among others (Table 1; see references therein). Native American, rural and urban populations consume some of these species as crude herbs or industrialized herbal medicines composed mainly of entire or broken dried leaves and often young stems, pods and flowers [7,8,9,10,11,12]. In general, plant materials are harvested from their natural habitats and prepared in aqueous infusions or teas, decoctions and tinctures [1,9,13]. In addition, B. forficata leaves are added to mate or chimarrão—a drink prepared with leaves of Ilex paraguariensis A. St.-Hil.—or used as an alcoholature [13,14]. Schnella microstachya is also consumed after meals in a preparation of leaves with cachaça, a local sugar cane brandy, termed “garrafada” [15]. In the case of commercial samples that are sold in open markets or herbalist shops, they sometimes present strange materials that are often labeled and traded by using common names, generic names or incorrect names and the identification of species from vegetative or fragmented material becomes complicated; thus, the botanical quality of the samples is not always adequate [16,17,18]. While B. forficata has been more extensively studied [19,20,21,22,23], the pharmacological properties of most of the regional species are less well known.
In this work, we have compiled records of bioactive properties of austral South American species reported in the literature in order to contribute to the knowledge of these promising medicinal entities.

2. Methods

A review of the literature available on the bioactivity of austral South American Bauhinia was conducted in January (2021) in the scientific databases Google Scholar and PubMed (Figure 1). The inclusion criteria were: (i) peer-reviewed articles published in journals listed in ScimagoJR [47] and/or indexed in Latindex [48]; (ii) English, Spanish and Portuguese literature; (iii) coverage time from 2000 to 2020. The exclusion criteria were: (i) studies published in non-indexed journals, theses, dissertations, conference proceedings and congress abstracts; (ii) patents; (iii) studies focusing on the structure of compounds or optimization of analytic methodologies.
The search terms used in combination were “Bauhinia”, the scientific binomial of each species, “biochemical properties”, “chemical composition”, “diabetes”, “medicinal”, “pharmacological”, “phytochemical”. We analyzed the following 19 taxa: B. affinis Vogel; B. amambayensis Fortunato; B. argentinensis Burkart var. argentinensis; B. argentinensis Burkart var. megasiphon (Burkart) Fortunato; B. bauhinioides (Mart.) J.F. Macbr.; B. campestris Malme; B. cheilantha (Bong.) Steud.; B. forficata Link. subsp. forficata; B. forficata Link. subsp. pruinosa (Vogel) Fortunato & Wunderlin (under the name B. candicans Benth.); B. hagenbeckii Harms; B. holophylla (Bong.) Steud.; Schnella microstachya Raddi var. microstachya (under the name B. microstachya (Raddi) J.F. Macbr. var. microstachya); S. microstachya var. massambabensis (Vaz) Trethowan & R. Clark (under the name B. microstachya (Raddi) J.F. Macbr. var. massambabensis Vaz); B. mollis (Bong.) D. Dietr. var. mollis; B. mollis (Bong.) D. Dietr. var. notophila (Griseb.) Fortunato; B. rufa (Bong.) Steud.; B. ungulata L. var. cuiabensis (Bong.) Vaz; B. ungulata L. var. ungulata; B. uruguayensis Benth. Subspecies and varieties were discriminated. In the case of B. forficata, taxa were cited following the nomenclature used by the authors in their papers.
During the search, 298 references where evaluated. After eliminating duplicates, the literature was selected on the basis of inclusion/exclusion criteria. In the review, 117 references were included.

3. Biological Activity

Biological activity has been reported for seven species: Bauhinia forficata, B. ungulata, B. bauhinioides, S. microstachya, B. holophylla, B. rufa and B. cheilantha. These activities are grouped into eight categories discussed in Section 3.1, Section 3.2, Section 3.3, Section 3.4, Section 3.5, Section 3.6, Section 3.7 and Section 3.8 in the text (Figure 2; Table 2); in particular, antidiabetic properties and related activities are shown in Table 3. Antidiabetic, antioxidant and antitumor and chemoprotective activities are the main categories published in the analyzed literature. The most studied taxon is B. forficata, which is one of the 71 plants belonging to the National Relation of Medicinal Plants of Interest of the Single Health System in Brazil [24]. Most of the activities are attributed to flavonoids, such as kaempferol, quercetin or myricetin derivatives, which have been characterized in five species with differential metabolite profiles (Table 4). Chemical constituents include terpenoids, alkaloids, steroids, phenolic acids and fatty acids, among others (Table 4).

3.1. Antioxidant Activity

Antioxidant activity can be relevant in diseases that involve an increased production of free radicals or impaired antioxidant defenses, such as in diabetes mellitus and its complications, cardiovascular diseases, cancer, inflammation and aging [154,155]. Antioxidant activity of different extracts has been demonstrated in vitro and in vivo in B. forficata, B. ungulata, S. microstachya and B. holophylla (Table 2). Among the most relevant results, B. forficata subsp. pruinosa leaf tea (1 mg/mL for 21 days) exerted a hepatoprotective effect, modulating the increase in liver oxidative damage and reducing NADPH quinone oxidoreductase 1 expression levels in the pancreas in streptozotocin-induced diabetic mice [84]. In pregnant streptozotocin-diabetic rats, treatment with B. forficata aqueous extracts (500–1000 mg/kg for 20 days) maintained a reduced glutathione concentration in the blood and contributed to a decreased incidence of fetal visceral anomalies in treated diabetic rats compared with the untreated ones [76]. Sampaio et al. [88] proposed a protective effect of flavonoids on the male genital system and they reported a reduction in malondialdehyde levels—a biomarker of lipid peroxidation—in testicular and epididymal tissues obtained from rats treated with alcoholic extracts (0.1 mL/10 g for 30 days) compared with controls. Peroza et al. [80] detected antioxidant activity in a model of orofacial dyskinesia in rats induced by antipsychotics (see Section 3.8). Interestingly, Pedrete et al. [156] detected oxidative stress-related proteins involved in peroxide degradation, such as succinate semialdehyde dehydrogenase 2-cis peroxiredoxin and alcohol dehydrogenase, in B. forficata proteome. The high-antioxidant capacity found by Mansur et al. [105] in various leaf extracts and fractions of B. microstachya var. massambabensis led the authors to formulate an oil-in-water photoprotective emulsion for cosmetic use, containing sunscreens/1% leaf extract [106]. Assays with different formulations, tested in vitro and in vivo with human volunteers, demonstrated that leaf extracts contribute to enhance the sun protection factor. Finally, a B. holophylla leaf hydroalcoholic extract (150 mg/kg) significantly increased the level of glutathione and the activities of glutathione peroxidase and glutathione reductase in rat stomachs with ethanol-induced gastric ulcers [97]. These antioxidant effects have been attributed to phenolic components, mostly flavonoids, such as kaempferitrin, quercetin and rutin (Table 4; e.g., [84,89,106,114]).

3.2. Antidiabetic Properties and Related Activities

Most taxa in the region are used in traditional medicine to prevent or treat diabetes mellitus (Table 1), a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both [157]. Bauhinia forficata is the most studied taxon, while B. holophylla has been recently explored (Figure 2; Table 3). Research has been conducted on different leaf extracts in vitro and orally administered in normoglycemic and hyperglycemic animal models. For the other taxa, no studies have been identified that clearly document their effective medicinal properties.

3.2.1. Bauhinia Forficata

Experimental diabetes induced by alloxan (ALX) or streptozotocin (STZ) produced hyperglycemia that was significantly reduced in acute, subacute and chronic treatments with leaf extracts in diabetic rats [68,125,132,134]) and rabbits [127]; moreover, acute treatments exerted hypoglycemic activity in normoglycemic rats and mice [125,131]. Furthermore, the extracts exerted a hypoglycemic effect in other models of hyperglycemia, such as the one induced by scorpion venom in rats [130]. On the contrary, it should be noticed that various chronic treatments failed to control glycemia [76,84,133]. Some treatments improved physiological or metabolic variables typically altered in the diabetic state, leading to a reduction in urine volume [127] and the urinary urea [124], as well as proteinuria and urine pH [134]. Regarding lipid metabolism, Lino et al. [129] demonstrated lipid-lowering properties with reduction in triglycerides (78–91%), total cholesterol (28–50%) and high-density lipoprotein (HDL) (27–68%) compared with diabetic controls, but other studies did not find changes in serum levels of different lipids [123,124,126,133]. Weight recovery was observed in treated diabetic animals by Curcio et al. [134] and this parameter, along with increased food and liquid intake, were not modified by other treatments [123,124,133]. Plant extracts reduced protein glycation in vitro; an activity that is important to decrease formation of advanced glycation end products (AGEs) produced during type 2 diabetes [86,89].
Regarding the hypoglycemic mechanism, an insulin-like effect has been hypothesized through peripheral glucose consumption, the regulation of key metabolizing enzymes, a delay in insulin catabolism or an increase in residual insulin efficiency or the inhibition of glucose reabsorption by the kidney (e.g., [74,78,125,135]). Increased glucose transport on peripheral tissues has been proved in isolated gastric glands [135]. Extracts inhibited in vitro enzymes such as α-glucosidase—which catalyzes the final step in the digestion of carbohydrates—and α-amylase and lipase, associated with postprandial hyperglycemia and hyperlipidemia in this metabolic disorder [78,86,89]. The increment of glycogen levels [126] suggests a regulation of glycogenolysis. Flavonoids, and particularly kaempferitrin (kaempferol 3,7-dirhamnoside), a major compound in both subspecies B. forficata leaves, are the main candidates for hypoglycemic action (Table 3 and Table 4). Acute treatment with purified kaempferitrin produced a significant hypoglycemic effect in diabetic [74,128] and normal rats [74]. Kaempferitrin favored peripheral glucose consumption, stimulating the glucose uptake in normal rat soleus muscle in vitro [128], involving synthesis, translocation and activation of the glucose transporter GLUT4 [136]. Glucose transport is mediated by the insulin signaling pathway that involves PI3K (phosphoinositide 3-kinase)-PKB (protein kinase B) and atypical PKC (protein kinase C) activation, together with the p38 MAPK (mitogen-activated protein kinase) pathway, which stimulates the expression of transporters or proteins from the insulin phosphorylation cascades [136]. Moreover, kaempferitrin stimulated in vitro glycogen synthesis and increased glycogen content in skeletal muscle [136]. On the other hand, Prasad et al. [158] showed that this compound from B. acuminata inhibits GLUT4 translocation. The role of kaempferitrin in glucose metabolism is demonstrated in other plants, where it stimulates 6-phosphofructo-1-kinase—the enzyme essential for controlling glycolysis—in the liver of diabetic mice, and other enzymes such as hexokinase and pyruvate kinase in myoblast cells [159]. Other compounds with potential hypoglycemic properties are the flavonoid rutin present in all subspecies of B. forficata and the alkaloid trigonelline identified in B. forficata subsp. pruinosa ([138]; Table 4). Pedrete et al. [156] identified enzymes of the glucose metabolism such as glyceraldehyde-3-phosphate dehydrogenases involved in glycolysis and gluconeogenesis and in controlling glucose levels and did not detect insulin-like proteins in B. forficata proteome.
Three clinical studies have been conducted in pre-diabetic or/and type 2 diabetic volunteers with B. forficata infusions (3–10 months), with effects neither in lowering fasting plasma glucose levels [137,138] nor in postprandial glycemia [139]. Auspiciously, a statistically significant reduction in the percentage of glycated hemoglobin (0.57% and 0.25%) was detected after the treatment in diabetic patients [138,139], respectively; these studies did not include control groups in their designs. Conversely, no reduction in glycated hemoglobin values was reported by Pozzobon et al. [137]. Mariángel et al. [139] detected a significant reduction of triglycerides (26%) and total cholesterol (9%), been not clinically significant; the changes in the lipid profile are attributed to trigonelline and rutin or other quercetin derivatives and flavonoids. These studies are based on small samples and the evidence is not conclusive. Thus, further researching is necessary to ensure clinical effects of infusions in the prevention or complementary treatment of diabetes in patients.

3.2.2. Bauhinia holophylla

Camaforte et al. [141] demonstrated hypoglycemic and hypolipidemic activities when administering ethanolic extracts to STZ diabetic mice. Fasting blood glucose decreased significantly (up to 50%), glucose tolerance improved and hepatic glycogen levels increased. The extracts also modulated gene and protein expressions of enzymes involved in carbohydrate metabolism. Then, the authors proposed that the extracts stimulate glycogenesis in the liver by inhibition of GSK3-β (glycogen synthase kinase 3β) through the PI3K/Akt (protein kinase B) pathway and inhibit gluconeogenesis. Furthermore, they favor the glucose uptake in the muscle by activation of the PI3K/Akt pathway. In addition, they favor the increase of the glucose transporter 4 (GLUT4) expression, stimulate glycogenesis in this tissue and inhibit intestinal α-glucosidase enzymes. In contrast, Pinheiro et al. [140] have previously reported non hypoglycemic effects in non-diabetic and STZ female diabetic rats and a possible toxic effect of this plant. HDL-cholesterol levels decreased in the treated diabetic group (40.2 ± 5.7 mg/dL) compared with untreated ones (61.9 ± 10.2 mg/dL). The authors warn about liver damage, since a reduction in the body weight of the treated diabetic rats was detected compared with the non-treated ones, along with increased activities of the hepatic enzymes alanine aminotransferase and aspartate aminotransferase. It is interesting to mention that, in this species, kaempferitrin has not been found; instead, flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol and isorhamnetin were reported (Table 4).
Discrepancies observed in the results in both species may be due to different variables. The plant-extraction method and the solvent used influence the chemical composition of the resultant extract and subsequently its biological activity. For instance, the non-extraction or absence of kaempferitrin in the extracts could explain negative or weak results found by Ferreres et al. [78], Farag et al. [83] and Salgueiro et al. [84]. The method of preparation is also critical, as in the case of the negative results and toxicity detected with spouted bed dried hydroalcoholic extracts of B. forficata [133]. The influence of environmental conditions on both the production and the concentration of active compounds should also be considered. Interestingly, kaempferitrin total flavonoid content or flavonoid profiles varied according to the sampling area, altitude and climate in B. forficata [146,160] or was influenced by edge-effect in B. cheilantha [161]. Adequate botanical identification is also essential. For instance, the subspecies of B. forficata are not identified in most assays; thus, flavonoid profiles—and some tested activities—present differences that could be related to variations at the subspecies level or plant misidentification [16,18]. Another variable to be considered is the experimental model selected for conducting the research [140,162]. For example, streptozotocin can induce mild or severe diabetes according to the dose, route of administration or animal strain utilized [163]. Chronic versus acute treatments could also present differences in results, as has been shown above. Thus, it is fundamental to guarantee the quality of the botanical samples, the accuracy of the chemical profiles and the deep research into the action mechanisms before their utilization as phytotherapeutics.

3.3. Analgesic Activity

Various studies support the popular therapeutic use of S. microstachya for the treatment of pain (Table 1 and Table 2). The methanolic extract (3–30 mg/kg) and the flavonoid quercitrin (1–10 mg/kg) isolated from leaves and administered intraperitoneally, caused potent and dose-related analgesic effects, inhibiting abdominal constrictions induced by an injection of acetic acid in mice (mean ID50 = 7.9 and 2.4 mg/kg, respectively) [39,101]. This extract elicited antinociceptive action against other models of pain such as capsaicin- and formalin-induced licking and was able to reverse, in a dose-related manner, the mechanical hyperalgesia in the rat paw induced by carrageenan, capsaicin, substance P, bradykinin and adrenaline [101]. Furthermore, methanol extract (0.1–2 mg/mL) and ethyl acetate fractions (0.1–2 mg/mL)—enriched in phenols and flavonoids—were found to have antispasmodic activity in vitro, inhibiting the contraction induced by different agonists in smooth muscle preparations of the guineapig ileum and the rat uterus [102].

3.4. Anti-inflammatory, Anti-ulcer and Wound Healing Activity

Anti-inflammatory properties mediated by Kunitz proteinase inhibitors isolated from seeds were described in B. bauhinioides and tested in animal models (Table 2). This type of inhibitor inhibits blood clotting enzymes, as well as other serine and cysteine proteinases ([164,165,166,167]). In particular, the B. bauhinioides cruzipain inhibitor (BbCI) inhibits the enzymes elastase, cathepsin L and cathepsin G [58,59], which are involved in inflammatory processes. Neuhof et al. [49] showed that the pulmonary edema in isolated rabbit lungs caused by activated neutrophils is significantly decreased by BbCI (10−5 M). Oliveira et al. [50] proved the effects of the pretreatment of BbCI in rat acute inflammatory models in vivo. BbCI (2.5 mg/kg, intravenous administration, 30 min before carrageenan-induced inflammation) reduced paw edema (24%, 44% and 40% at 2, 3 and 4 h after carrageenan injection, respectively) and the release of the inflammatory mediator bradykinin. It reduced (39%) neutrophil migration into the pleural cavity in a model of pleurisy, as well as the number of rolling, adhered and migrated leucocytes at the spermatic fascia microcirculation in the scrotum. In addition, there was a significant decrease in levels of another mediator, cytokine-induced neutrophil chemo-attractant-1, in the pleural exudate and serum in the inflamed rats. The B. bauhinioides kallikrein inhibitor (BbKI) inhibits trypsin, chymotrypsin, plasmin and pancreatic and plasma kallikrein [59,60]. Recombinant rBbKI (2 mg/kg intraperitoneal administration on days 1, 15 and 21) was tested in a model of elastase-induced pulmonary inflammation in mice. Martins-Olivera et al. [53] found that rBbKI treatment attenuated various mechanical alterations of the lung and alveolar septum disruption and reduced the number of inflammatory cells in the bronchoalveolar lavage fluid. In addition, it reduced the cellular expression of several markers of inflammatory recruitment, remodeling the extracellular matrix and oxidative stress responses in airways and alveolar walls, all of which are events involved in the development of chronic obstructive pulmonary disease. Furthermore, rBbCI (2 mg/kg intraperitoneal administration on days 1, 15 and 21) ameliorated the pulmonary mechanics’ changes in C57BL/6 mice elastase-induced pulmonary emphysema, reducing lung tissue destruction, inflammatory alterations, extracellular matrix remodeling and oxidative stress in the alveolar septa and airway walls [52].
Lectins isolated from seeds are also involved in anti-inflammatory activities. The B. bauhinioides lectin (BBL) was tested in two acute models of inflammation in rats, paw edema and peritonitis. BBL (1 mg/kg intravenously 30 min before carrageenan-induced inflammation) inhibited the paw edema in the second phase (21% and 19% at 3 and 4 h, respectively) [51]. It also inhibited peritoneal neutrophil migration (51% and 64%, when induced by carrageenan and tumor necrosis factor TNF-α, respectively), and decreased leukocyte rolling (58%) and adhesion (68%). The reduction of TNF-α and IL1-β levels would be responsible for anti-inflammatory activity.
Anti-ulcer activity was reported in B. holophylla. Leaf hydroalcoholic extracts enriched in quercetin and myricetin (150 mg/kg oral administration) decreased oxidative stress, attenuated the inflammatory response and favored an antidiarrheal effect in ethanol-induced gastric ulcer in rats [97]. The anti-inflammatory activities were evaluated as the decrease in the production of the pro-inflammatory cytokines TNF-α and interleukin-6 (IL-6) and the increase of the level of the anti-inflammatory cytokine IL-1 [97]. Anti-ulcer activity has also been described in models of acute gastric lesion induced in rats or mice, and aqueous extracts promoted an increase in the amount of gastric mucus [99]. The potential gastroprotective activity is possibly mediated by flavonols.
Regarding wound healing activities, Rodrigues et al. [119] evaluated ethyl acetate fraction from B. ungulata stem bark (FABU 10, 100 μg/mL) using monolayers of human lung adenocarcinoma A549 epithelial cells that were split in the middle. They found that, after 24-h treatment, the cell migration process was accelerated and the initial lesion gap was reduced (32.6–22.0%) compared with the control group. Moreover, they found that a 5-day topical treatment (200 μL of 0.25 or 0.5% w/v FABU extract gel) significantly reduced a lesion effectuated in the dorsal surface of C57BL/6 mice compared with an untreated control group. Local anti-inflammatory and antioxidant properties were detected, with a reduction of relative expressions of TNFα and IL-1β (50%, FABU at 0.5%) and a reduction of levels of lipid peroxidation (FABU at 0.25% and 0.5%).

3.5. Antitumor and Chemoprotective Activity

In the search for natural products for their application in cancer diagnosis or complementary therapy, some promising compounds and extracts have been characterized in six species of Bauhinia (Table 2). Moreover, some of them may help to prevent or minimize chemotherapy side effects.
Plant lectins specifically and reversibly bind to different types of carbohydrates or glycoproteins. The alteration of the glycosylation profile of cell surfaces indicates carcinogenesis; lectins have been used in diagnosis or as alternative anticancer drugs [168]. For instance, the glycoprotein B. forficata lectin (BfL), purified from B. forficata subsp. forficata seeds, showed a selective cytotoxic effect (2.5–10 μM) and adhesion inhibition (1 μM) on MCF-7 human breast cancer cells [95]. BfL induced cell death by triggering necrosis and secondary necrosis, with caspase-9 inhibition, and it caused DNA fragmentation, which resulted in cell cycle arrest in the G2/M phase. It also inhibited cell adhesion to laminin, fibronectin and collagen type I, with reduced α1, α6 and β1 integrin subunit expression [95]. Lubkowski et al. [94] evaluated the toxicity of recombinant BfL (1.85 μM) on an NCI-60 panel, which allowed the screening of 60 human cancer cells lines. rBfL showed cytostatic activity and no cytotoxic effects, inhibiting the growth of several cancer cell lines. Inhibition was strong for 5 tumor cell lines (>50%) and moderate for 22 cell lines (10–50%) [94]. In B. ungulata, a new galactose-binding lectin—termed BUL—purified from seeds (60–160 µg/mL), showed antiproliferative activity against the HT-29 cell line of human colon adenocarcinoma in a dose-dependent manner [116]. At the most concentrated dose (160 µg/mL), BUL inhibited 80% of cell growth viability.
Other natural compounds have been isolated from Bauhinia plants. Treatment with B. forficata HY53 for 24 h inhibited growth in a dose-dependent manner (0.07–0.4 mM, IC50 = 0.13 mM) and induced apoptosis of human hepatocellular carcinoma Hep-G2 cells (apoptotic cell population increased from 8% at 0 mM to 45% at 0.4 mM). Apoptosis would involve activation of caspase-3, a major downstream effector of this process, and then the cleavage of poly(ADP-ribose) polymerase (PARP), critical steps leading to subsequent DNA fragmentation and condensation [91]. In addition, treatment with HY52 for 24 h had an antiproliferative effect (0.07 to 0.41 mM; IC50 = 0.11 mM) and induced apoptosis (at 0.14 mM, the apoptotic cell population increased from 3% at 0 h to 37% at 24 h) on human cervical adenocarcinoma HeLa cells by regulating proteins involved in cell-cycle progression. It induced a G1-phase arrest by inhibiting phosphorylation of retinoblastoma protein pRb via up-regulation of p21WAF1/CIP1 and p27KIP1, and G2/M-phase arrest by downregulation of CDC2 kinase, cyclins A and B1 [92]. Bibenzyl, isolated from the roots of B. ungulata, displayed cytotoxicity against pro-myelocytic leukemia (HL-60) and cervical adenocarcinoma (HEP-2) cell lines (IC50 = 4.3 and 6.5 mg/kg, respectively) [118].
Kunitz proteinase inhibitors also mediated effects on cell adhesion and proliferation. Both B. bauhinioides BbCI and BbKI reduced HUVEC human umbilical vein endothelial cell proliferation in a concentration-dependent manner [55,56]. Furthermore, compared with chemotherapy cytotoxic drug 5-fluorouracil, recombinant BbCI and rBbKI were more efficient in inhibiting various tumor cell lines [57]. The B. rufa trypsin inhibitor (BrTI) and a synthetic peptide containing an RGD motif inhibited cell adhesion to fibronectin of B16F10 and Tm5 murine melanoma cells [109]. In addition, rBbKIm—a recombinant BbKI modified to include the RGD/RGE motifs of the inhibitor BrTI—inhibited the cell viability of prostate cancer cells DU145 and PC3 [108]. In both cancer cell lines, rBbKIm triggered apoptosis and cytochrome c release into the cytosol. rBbKIm caused an arrest at the G0/G1 and G2/M phases and activation of caspase-9 in PC3 cells, whereas, in DU145 cells, the cell cycle was not affected and rBbKIm activated caspase-3 cells. Moreover, it inhibited the in vitro capillary-like tube network formation in HUVECs endothelial cells, which is important to reduce angiogenesis involved in the development of a tumor [108].
Some cytotoxic assays have been developed with the essential oils of Bauhinia leaves. B. ungulata essential oils exhibited cytotoxic activity against human cancer cell lines HL-60, MCF-7, NCI-H292 and HEP-2, with IC50 ranging from 10.6 µg/mL to 26.6 µg/mL [117]. B. cheilantha essential oils also showed in vitro cytotoxic activity against the same human tumor cell lines HL-60, MCF-7, NCI-H292 and HEP-2 (IC50 = 8.6, 18.3, 33.1 and >50 mg/mL, respectively) [61].
Bauhinia plant extracts or fractions have also shown antitumor and/or chemoprotective effects. For instance, B. ungulata extracts of stems, enriched in flavonoids and alkaloids, inhibited the activity of matrix metalloproteinases MMP-2 and MMP-9, which cleave the main structural components of the basal membrane and have a prognostic influence on human cancers [121]. More recently, Ribeiro et al. [98] found that B. holophylla hydroalcoholic extract induced apoptosis and showed high antiproliferative effects in Hep-G2 cells. The extract did not induce mutagenicity at three concentrations tested and had protective effects against DNA damage produced by carcinogenic agents such as benzo[a]pyrene (B[a]P). Aqueous extracts of B. forficata have antimutagenic/protective action on bone marrow cells of Wistar rats; they reduced chromosomal alterations induced by the chemotherapeutic agent cyclophosphamide [96]. B. forficata flavonoid-rich fraction and purified kaempferitrin protected intestinal cells (IEC-6 cells) from cytotoxicity induced by irinotecan [93]. This chemotherapy agent—used to treat colorectal cancer—produces side effects such as damage in intestinal mucosa and mucositis. The flavonoid-rich fraction (100 mg/kg/day oral administration for 14 days) prevented mucositis in mice (attenuating diarrhea and histological damage in the duodenum and the colon, among other tested parameters), without interfering in irinotecan antitumor activity. Furthermore, this fraction produced a significant antitumoral effect on a murine melanoma model.

3.6. Antimicrobial Activity

Concerning antimicrobial activity, Alves et al. [70] showed that B. forficata leaf ethanolic extracts had antimicrobial activity against Candida albicans. Sousa et al. [73] did not detect activity against C. albicans, Escherichia coli or Staphylococcus aureus species, but the extracts increased the effectiveness of norfloxacin against the S. aureus SA1199-B with a concentration-dependent effect. This strain overproduces the NorA efflux pump, a transmembrane protein that extrudes antimicrobial compounds, such as norfloxacin. Thus, B. forficata extract could be potentially used—together with norfloxacin—to treat infections caused by multidrug-resistant S. aureus [73]. Ferreira-Filho et al. [71,72] showed antimicrobial effects of B. forficata leaf tincture (20% in a 70% hydroethanolic solution) against oral microorganism strains and mature dental biofilms obtained from salivary samples and formed on membranes or bovine enamel blocks. The tincture is a promising preventive agent of dental caries, with no cytotoxic effect, tested against oral fibroblast cells. Miceli et al. [35], however, did not detect an antimicrobial effect against different strains of bacteria and yeasts, nor did Simões and Almeida [169] with an ethanolic extract of stem bark against Klebsiella pneumoniae, E. coli and S. aureus. Aqueous and ethanolic extracts of B. rufa presented antimicrobial activity against Candida spp. [107] and B. ungulata aqueous and esential oils presented antimicrobial activity against various pathogenic microorganisms alone (Medeiros et al. [113] or in synergy with antibiotics [112].

3.7. Anticoagulant, Antithrombotic, Antihypertensive and Diuretic Activity

Since the Kunitz proteinase inhibitor BbKI form B. bauhinioides is active against enzymes involved in coagulation processes, fibrinolysis and inflammation, Brito et al. [54] evaluated its antithrombotic activity in vein and arterial thrombosis models in rat and mice, respectively. They found that BbKI (2.0 mg/kg) reduced the venous thrombus weight by 65% and prolonged the time for total artery occlusion (87.27 ± 14.94 min) in comparison with animals in the control groups (51.97 ± 10.52 min); these results indicated thrombosis prevention. The lectine BfL—from B. forficata subsp. forficata—exhibited anticoagulant and antiplatelet aggregating properties in biological models of homeostasis in vitro [64]. Purified BfL (1.5–4 µM) increased coagulation time (an effect not related to human plasma kallikrein or human factor Xa inhibition) and inhibited ADP and epinephrine-induced platelet aggregation in a dose-dependent manner. B. rufa hexane extracts of leaves produced 26.11% of clot lysis from human venous blood [110].
Regarding vasorelaxant properties, it has been demonstrated that aqueous–ethanol extracts of leaves of B. candicans (120 mg/kg/day for 2 weeks) increased the endothelium-dependent relaxation of phenylephrine-precontracted aortic rings in ALX diabetic rats; this effect was attributed to the antioxidant activity mediated by flavonoids [68]. Acetylcholine-induced relaxation of aortic rings was greater in diabetic rats treated with extracts than in untreated diabetic rats. The vasorelaxant properties of ethyl acetate plus butanol fraction from B. forficata leaves (1–50 μg/mL) were also described in aortic rings of both normotensive and hypertensive rats precontracted with phenylephrine [69]. The effect was found in aorta rings with intact endothelium and endothelium-denuded aorta. The modulation of vascular tone would be related with the nitric oxide/soluble guanylate cyclase pathway, since the incubation with a non-selective nitric oxide synthase inhibitor (L-NAME) or a soluble guanylate cyclase inhibitor (ODQ) blocked the vasorelaxant activities of the extract. Potassium channels and membrane hyperpolarization would also be involved in vascular tone. The flavonoids kaempferitrin and kaempferol (0.001–0.3 μg/mL) showed a vasorelaxant potential of 34.70% and 40.54%, respectively. Anjos et al. [66] found that the aqueous extract of B. forficata (5–40 mg/kg intravenous administration) presented antihypertensive effects, inducing a dose-dependent transitory hypotension and tachycardia in normotensive rats and reducing mean arterial pressure by 12% in hypertensive rats (oral acute dose of 400 mg/kg). These effects seem to involve the release of nitric oxide.
Bauhinia forficata is popularly consumed for kidney and urinary disorders such as polyuria, cystitis and kidney stones (Table 1). Debenedetti et al. [170] could not demonstrate diuretic properties with plant infusions in rats (250, 500 and 1000 mg/kg oral administration). Afterwards, Toloza-Zambrano et al. [138] reported an increase in diuresis in human diabetic patients consuming leaf infusions (see Section 3.1). More recently, Souza et al. [67] have reported diuretic and natriuretic properties of leaf extracts. When orally treated with leaf aqueous infusion (300 mg/kg) and other fractions, urine volume and electrolyte levels significantly increased after 8 h in both normotensive and spontaneously hypertensive rats compared with controls, with no changes in pH, density or conductivity parameters. Moreover, isolated kaempferitrin (0.3 and 1 mg/kg) induced diuresis and saluresis and augmented excretion of urinary creatinine and prostaglandin E2. Diuretic action should be related with the generation of prostanoids, since this activity is affected by treatment with the cyclooxygenase inhibitor indomethacin. Further, it was demonstrated that afzelin—a flavonoid from the kaempferitrin metabolic route—but not kaempferol, presents acute and prolonged diuretic action and renal protective action; diuresis should involve endogenous prostanoid generation and muscarinic receptor activation [171].
Thus, these plants could play an interesting role as alternative pharmacotherapies in renal or cardiovascular disorders [69,171]. Moreover, endothelial dysfunction [68] or hypertension [66] are sometimes associated with diabetes.

3.8. Other Biological Activities

Other diverse biological activities have been described in austral South American Bauhinia species (Table 2). The chronic use of antipsychotics can trigger adverse motor effects such as the repetitive involuntary movements seen in tardive dyskinesia in humans. Since these disturbances seem to be related to oxidative stress in some areas of the brain, Peroza et al. [80] investigated the effects of B. forficata on brain lipid peroxidation in a model of orofacial dyskinesia in rats induced by long-term treatment with the antipsychotic haloperidol (38 mg/kg every 28 days). Plant decoction (250–300 mg/kg/day for 16 weeks) prevented the formation of lipid peroxidation induced by two pro-oxidants tested. Moreover, it partially diminished the vacuous chewing movements induced by haloperidol.
The B. bauhinioides BbCI inhibition of cruzipain—a cysteine proteinase from Trypanosoma cruzi—has shown the potential of this species for the development of anti-Chagas drugs [58,59]. Santos et al. [100] reported that hydroethanolic extracts of B. holophylla, enriched in flavonoids, presented a potent activity (IC50 = 3.2 µg/mL, selectivity index = 27.6) against the Dengue virus serotype DENV-2, which is transmitted by mosquitoes. Leaf essential oils of B. cheilantha and B. ungulata showed larvicidal potential against instar III larvae of the Aedes aegypti mosquito (LC50 = 40.84 ± 0.87 mg/mL; LC50 = 75.1 ± 2.8 µg/mL, respectively) [61,117]. Other Bauhinia extracts presented larvicidal activity against A. aegypti (B. cheilantha, woods and seeds) and Culex quinquefasciatus (B. rufa, leaves) [62,63,111]).
Hydromethanolic extracts of leaves of both subspecies of B. forficata exhibited some activity against cholinesterases (acetyl- or butyrylcholinesterase) [78], whereas hexane extracts of flowers and leaf essential oils of B. ungulata inhibited acetylcholinesterase [113,120]. These enzymes are associated with the etiology of Alzheimer’s disease; therefore, these species may potentially contribute to the treatment of this pathology [78].
Oliveira et al. [65]) found that the aqueous extract of the aerial parts of B. forficata is a promising source of natural inhibitors of the serine proteases involved in blood clotting disturbances induced by snake venoms. The extract neutralized the clotting activity induced by the Bothrops and Crotalus crude venoms and inhibited clotting and fibrinogenolytic activities induced by the isolated thrombin-like enzyme from the Bo. jararacussu venom. It also inhibited the edema induced by C. durissus terrificus venom in mice. On the other side, B. forficata extracts enhanced the Tityus serrulatus scorpion venom’s lethality [130].
Finally, the presence of lectins and Kunitz inhibitor activities could have potential uses that still have not been explored [164,165,166,168]. For instance, Castro et al. [172] have produced and characterized a lectin from the primary callus cultures of B. holophylla. Other proteinase inhibitors (BuXI) and their target proteinases have been characterized in B. ungulata [122] and two isoforms of Kunitz-type trypsin inhibitor-like 1(BrTI and α-chain) were identified in a B. forficata proteome [156].

3.9. Toxicity and Adverse Effects

Toxic effects were not reported in most methodological approaches (e.g., [72,76,84,89,97,138,141,173]), however some research findings deserve attention. It has been reported that acute treatment with B. forficata crude extract (2.85 g/kg) injected intraperitoneally caused the death of 50% of the animals, yet oral administration (0.5 to 5.0 g/kg) is not toxic [1]. The increment in hepatic toxicity markers triggered by B. forficata spouted bed-dried extract and B. holophyla aqueous extracts in treated diabetic rats suggests liver injury (see Section 3.1) [133,140]. In the first case, this could be attributed to secondary product formation or interaction with Tixosil employed in the experiments. Low toxicity was reported for B. forficata stem bark ethanolic extracts in Artemia salina tests (CL50 = 853.80 μg/mL) and the authors recommended a dilution when preparing formulations, teas and garrafadas [169]. Cavalcanti et al. [174] warned about toxicologic effects of B. forficata aqueous extracts (5 g/kg oral administration), since they detected alterations in behavior in rat anxiolytic models, such as decreased general activity and increased grooming duration and pentobarbital sleep inducing time; these authors suggest a dosage for central neurotransmitters. Sampaio et al. [88] reported damage in epididymal tissues in rats treated with B. forficata extracts (0.1 mL/10 g body weight/day alcoholic extract for 30 days). Mitochondrial damage was also reported by Ecker et al. [82] in isolated rat liver mitochondria exposed to B. forficata aqueous extracts in vitro. They detected a decrease in mitochondrial dehydrogenase activity at high concentrations of extracts (200 and 400 μg/mL) and an induction of swelling (at 25 and 400 μg/mL). Finally, by interviewing 100 Bauhinia spp. consumers in Diadema, Sau Paulo (Brazil), Neto et al. [175] reported adverse reactions in two persons (mother and daughter) who presented a strong allergic reaction after the consumption of tea and had to be hospitalized; the causes were unclassifiable by the authors. They informed of four records of severe reactions after consumption of an unregistered medication of B. forficata (hepatic problems, such as cirrhosis and renal pain), published by the Brazilian sanitary vigilance agency; they did not find similar reports in the literature searches. Thus, it is important to further investigate the possible adverse effects of the consumption of the Bauhinia species in order to minimize the health risk.

4. Conclusions

Bauhinia forficata, B. ungulata, B. bauhinioides, S. microstachya, B. holophylla, B. rufa and B. cheilantha are the austral South American species with records of pharmacological properties that explain their various ethnopharmacological uses. Bauhinia forficata is the most consumed and studied plant, with antidiabetic, antioxidant, anticoagulant, antihypertensive, diuretic, antimicrobial and antitumor properties. Together with B. holophylla, they are important for their antidiabetic properties, since several studies indicate their effectiveness as a hypoglycemic agent. Conflicting results could be explained by differences in extraction methods and preparation, chemical profiles, route of administration and dose, treatment periods, animal models used or plant identification. Clinical studies in B. forficata are still preliminary and deserve further investigation. B. bauhinioides is distinguished for its anti-inflammatory and antithrombotic activities mediated by Kunitz-type inhibitors. S. microstachya is distinguished for its analgesic properties. Anti-ulcer and wound healing activities recorded in B. holophylla and B. ungulata, respectively, are of particular interest. Most of the species possess antitumor activity, mediated by lectins, Kunitz proteinase inhibitors and other compounds. B. forficata extracts alleviate the side effects of chemotherapy, such as intestinal mucositis. The antioxidant capacity of flavonoids and other bioactive compounds present in B. forficata, S. microstachya, B. ungulata and B. holophylla make these plants good candidates for assisting or treating various alterations related with oxidative stress, such as diabetic complications and gastric ulcer, or even for cosmetic use. Thus, these regional species constitute promising targets for new bioactive substance research and phytotherapy.

Author Contributions

Conceptualization, writing—original draft preparation, supervision, project administration, R.H.F.; methodology, formal analysis, investigation, data curation, funding acquisition, writing—review and editing, R.H.F. and M.J.N. All authors have read and agreed to the published version of the manuscript.

Funding

This was funded by Consejo Nacional de Investigaciones Científicas y Técnicas, PIP 112-201101-00250; Instituto Nacional de Tecnología Agropecuaria, PNHFA-1106094; Secretaría de Ciencia y Tecnología—Universidad Nacional de Córdoba, 32720160200161CB; Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, PICT 2019-2683 and PICT 2019-316.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Neto, J.A.S.; Galduróz, J.C.F.; Marques, L.C.; Kato, E.T.; Macrini, T.; Rodrigues, E. Possible adverse reactions to herbal products: A study with individuals who resort to popular medicine in the city of Diadema, SP, Brazil. Phytother. Res. 2014, 28, 405–411. [Google Scholar] [CrossRef] [PubMed]
  2. Silva, K.L.; Cechinel Filho, V. Plantas do gênero Bauhinia: Composição química e potencial farmacológico. Quim. Nova 2002, 25, 449–454. [Google Scholar] [CrossRef]
  3. Cechinel Filho, V. Chemical composition and biological potential of plants from the genus Bauhinia. Phytother. Res. 2009, 23, 1347–1354. [Google Scholar] [CrossRef]
  4. Caffaro, K.M.; Araújo Júnior, J.X.; Santos, J.M.; Santos, R.M.; Campesatto, E.A.; Bastos, M.L.A. Integrative review on medical use and pharmacological activities Bauhinia genus plant. J. Nurs. UFPE 2015, 9, 9399–9405. [Google Scholar]
  5. Fortunato, R.H. Revisión del género Bauhinia (Cercideae, Caesalpinioideae, Fabaceae). Darwiniana 1986, 27, 527–557. [Google Scholar]
  6. Fortunato, R.H.; Miotto, S.; Izaguirre, P.; Beyhaut, R.; Bortoluzzi, R.L.C.; Ulibarri, E.; Gómez-Sosa, E. Fabaceae. In Catálogo de las Plantas Vasculares del Cono Sur; Zuloaga, F.O., Morrone, O., Belgrano, M.J., Eds.; Missouri Botanical Garden Press: Buenos Aires, Argentina, 2008; Volume 107, pp. 2078–2319. [Google Scholar]
  7. Vaz, A.M.S.F.; Bortoluzzi, R.L.C.; Silva, L.A.E. Checklist of Bauhinia sensu stricto (Caesalpiniaceae) in Brazil. Plant Ecol. Evol. 2010, 143, 212–221. [Google Scholar] [CrossRef]
  8. Rondina, R.V.D.; Bandoni, A.L.; Coussio, J.D. Especies medicinales argentinas con potencial actividad analgésica. Dominguezia 2008, 24, 47–69. [Google Scholar]
  9. Basualdo, I.; Soria, N. Plantas medicinales comercializadas en el mercado municipal de la ciudad de Pilar, Dpto. Ã ‘eembuc, Paraguay. Dominguezia 2014, 30, 47–53. [Google Scholar]
  10. Arias Toledo, B.; Trillo, C.; Grilli, M. Uso de plantas medicinales en relación al estado de conservación del bosque en Córdoba, Argentina. Ecología austral. 2010, 20, 235–246. [Google Scholar]
  11. Morais, S.M.; Dantas, J.D.P.; Silva, A.R.A.; Magalhães, E.F. Ethno-medicinal plants of Tapeba Indians from the State of Ceará-Brazil. Rev. Bras. Farmacogn. 2005, 15, 169–177. [Google Scholar] [CrossRef] [Green Version]
  12. Ibarrola, D.A.; Degen de Arrúa, R.L. Catálogo Ilustrado de 80 Plantas Medicinales del Paraguay; Facultad de Ciencias Químicas-UNA, Agencia de Cooperación International del Japón (JICA): Asunción, Paraguay, 2011. [Google Scholar]
  13. Coelho-Ferreira, M. Medicinal knowledge and plant utilization in an Amazonian coastal community of Marudá, Pará State (Brazil). J. Ethnopharmacol. 2009, 126, 159–175. [Google Scholar] [CrossRef] [PubMed]
  14. Miceli, N.; Buongiorno, L.P.; Celi, M.G.; Cacciola, F.; Dugo, P.; Donato, P.; Mondello, L.; Bonaccorsi, I.; Taviano, M.F. Role of the flavonoid-rich fraction in the antioxidant and cytotoxic activities of Bauhinia forficata Link. (Fabaceae) leaves extract. Nat. Prod. Res. 2016, 30, 1229–1239. [Google Scholar] [CrossRef] [PubMed]
  15. Silva, G.L.C.; Gaertner, P.; Marson, P.G.; Schwarz, E.D.A.; Santos, C.A.D.M. An ethno-pharmacobotanical survey in Salto Caxias hydroelectric power plant in Paraná State, Brazil, before the flooding. Acta Farm. Bonaerense. 2004, 23, 148–153. [Google Scholar]
  16. Leitão, F.; Leitão, S.G.; Fonseca-Kruel, V.S.D.; Silva, I.M.; Martins, K. Medicinal plants traded in the open-air markets in the State of Rio de Janeiro, Brazil: An overview on their botanical diversity and toxicological potential. Rev. Bras. Farmacogn. 2014, 24, 225–247. [Google Scholar] [CrossRef]
  17. Melo, J.D.; Nascimento, V.D.; Amorim, E.D.; Lima, C.S.A.; Albuquerque, U.D. Avaliação da qualidade de amostras comerciais de boldo (Peumus boldus Molina), pata-de-vaca (Bauhinia spp.) e ginco (Ginkgo biloba L.). Rev. Bras. Farmacogn. 2004, 14, 111–120. [Google Scholar] [CrossRef] [Green Version]
  18. Engel, I.C.; Ferreira, R.A.; Cechinel-Filho, V.; Meyre-Silva, C. Quality control of drugs with Bauhinia forficata Link (Fabaceae). Rev. Bras. Farmacogn. 2008, 18, 258–264. [Google Scholar] [CrossRef]
  19. Fortunato, R.H.; Varela, B.G.; Castro, M.A.; Nores, M.J. Leaf venation pattern to recognize austral South American medicinal species of “cow’s hoof” (Bauhinia L.; Fabaceae). Rev. Bras. Farmacogn. 2017, 27, 158–161. [Google Scholar] [CrossRef]
  20. Batista, P.N.; Oliveira, T.C.; Leal, F.R.; Graccedil, M.; Nunes, L.C.C. The influence of using Bauhinia forficata Link in glycemic, lipid and toxicological profile in vivo experimental models: A systematic review. J. Med. Plants Res. 2013, 7, 2343–2348. [Google Scholar]
  21. Marques, G.S.; Rolim, L.A.; Alves, L.D.S.; Silva, C.C.A.R.; Soares, L.A.L.; Rolim-Neto, P.J. Estado da arte de Bauhinia forficata Link (Fabaceae) como alternativa terapêutica para o tratamento do diabetes mellitus. Rev. Cienc. Farm. Basica Apl. 2013, 34, 313–320. [Google Scholar]
  22. Cechinel-Zanchett, C.C.; Andrade, S.F.; Cechinel-Filho, V. Ethnopharmacological, phytochemical, pharmacological and toxicological aspects of Bauhinia forficata: A mini-review covering the last five years. Nat. Prod. Commun. 2018, 13, 911–916. [Google Scholar]
  23. Pontes, M.A.N.; Lima, D.S.; Oliveira, H.M.B.F.; Oliveira Filho, A.A. Bauhinia forficata L. and its hypoglycemic action. Arch. Health Invest. 2017, 6, 509–512. [Google Scholar] [CrossRef] [Green Version]
  24. Bortoluzzi, R.L.C.; Miotto, S.T.S.; Reis, A. Bauhinia L. In Flora Ilustrada Catarinense 2; Reis, A., Ed.; Herbário Barbosa Rodrigues: Itajaí, Brazil, 2006; pp. 29–67. [Google Scholar]
  25. RENISUS. Relação Nacional de Plantas Medicinais de Interesse ao SUS; Programa de Fitoterápico e Plantas Medicinais; Ministério da Saúde: Brasília, Brasil; 2009. Available online: https://www.gov.br/saude/pt-br/acesso-a-informacao/acoes-e-programas/programa-de-fitoterapico-e-plantas-medicinais (accessed on 15 August 2019).
  26. Barboza, G.E.; Cantero, J.J.; Núñez, C.; Pacciaroni, A.; Ariza Espinar, L. Medicinal plants: A general review and a phytochemical and ethnopharmacological screening of the native Argentine Flora. Kurtziana 2009, 34, 7–365. [Google Scholar]
  27. Basualdo, I.; Soria, N.; Ortíz, M.; Degen, R. Plantas medicinales comercializadas en los mercados de Asunción y Gran Asunción. Rojasiana 2004, 6, 95–114. [Google Scholar]
  28. Almeida, C.; Silva, T.D.L.E.; de Amorim, E.; Maia, M.D.S.; de Albuquerque, U. Life strategy and chemical composition as predictors of the selection of medicinal plants from the caatinga (Northeast Brazil). J. Arid Environ. 2005, 62, 127–142. [Google Scholar] [CrossRef]
  29. Albuquerque, U.P.; Medeiros, P.M.; Almeida, A.L.S.; Monteiro, J.M.; Neto, E.M.F.L.; Melo, J.G.; Santos, J.P. Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: A quantitative approach. J. Ethnopharmacol. 2007, 114, 325–354. [Google Scholar] [CrossRef] [PubMed]
  30. Pizziolo, V.R.; Brasileiro, B.G.; Oliveira, T.T.; Nagem, T.J. Plantas com possível atividade hipolipidêmica: Uma revisão bibliográfica de libros editados no Brasil entre 1998 e 2008. Rev. Bras. Plant. Med. 2011, 13, 98–109. [Google Scholar] [CrossRef]
  31. Macedo, J.G.F.; de Menezes, I.R.A.; Ribeiro, D.A.; de Oliveira Santos, M.; de Mâcedo, D.G.; Macêdo, M.J.F.; de Almeida, B.V.; de Oliveira, L.G.S.; Leite, C.P.; Souza, M.M.D.A. Analysis of the variability of therapeutic indications of medicinal species in the Northeast of Brazil: Comparative study. Evid.-Based Complement. Altern. Med. 2018, 2018, 1–18. [Google Scholar] [CrossRef] [Green Version]
  32. Keller, H.A. Unidades de vegetación y recursos florísticos en una aldea Mbya Guaraní de Misiones, Argentina. Kurtziana 2007, 33, 175–191. [Google Scholar]
  33. Trojan-Rodrigues, M.; Alves, T.L.S.; Soares, G.L.G.; Ritter, M.R. Plants used as antidiabetics in popular medicine in Rio Grande do Sul, southern Brazil. J. Ethnopharmacol. 2012, 139, 155–163. [Google Scholar] [CrossRef] [Green Version]
  34. Bolson, M.; Hefler, S.R.; Chaves, E.I.D.; Gasparotto Junior, A.; Cardozo Junior, E.L. Ethno-medicinal study of plants used for treatment of human ailments, with residents of the surrounding region of forest fragments of Paraná, Brazil. J. Ethnopharmacol. 2015, 161, 1–10. [Google Scholar] [CrossRef]
  35. Soria, N.; Ramos, P. Uso de plantas medicinales en la atención primaria de Salud en Paraguay: Algunas consideraciones para su uso seguro y eficaz. Mem. Inst. Investig. Cienc. Salud. 2015, 13, 8–17. [Google Scholar] [CrossRef]
  36. Salgueiro, A.C.F.; Folmer, V.; Bassante, F.E.M.; Cardoso, M.H.S.; Rosa, H.S.; Puntel, G.O. Predictive antidiabetic activities of plants used by persons with Diabetes mellitus. Complement. Ther. Med. 2018, 41, 1–9. [Google Scholar] [CrossRef] [PubMed]
  37. Hurrell, J.A.; Ulibarri, E.A.; Puentes, J.P.; Buet Costantino, F.; Arenas, P.M.; Pochettino, M.L. Leguminosas medicinales y alimenticias utilizadas en la conurbación Buenos Aires-La Plata, Argentina. Bol. Latinoam. Caribe Plant. Med. Aromat. 2011, 10, 443–455. [Google Scholar]
  38. Martínez Crovetto, R.N. Estudios Etnobotánicos, V. Nombres de plantas y su utilidad según los Mbya Guaraní de Misiones, Argentina. Bonplandia 2012, 21, 109–133. [Google Scholar] [CrossRef] [Green Version]
  39. Tabakian, G. Estudio comparativo de plantas medicinales vinculadas a tradiciones indígenas y europeas en Uruguay. Bonplandia 2019, 28, 135–158. [Google Scholar] [CrossRef]
  40. Meyre-Silva, C.; Yunes, R.A.; Monache, F.D.; Santos, A.R.S.; Schmeling, L.O.; Gadotti, V.M.; Liz, F.; Cechinel Filho, V. Phytochemical and pharmacological analysis of Bauhinia microstachya (Raddi) Macbr. (Leguminosae). Z. Naturforsch. C 2001, 56, 939–942. [Google Scholar]
  41. Silva, E.G.; Behr, G.A.; Zanotto-Filho, A.; Lorenzi, R.; Pasquali, M.A.D.B.; Ravazolo, L.G.; Bordignon, C.L., Jr.; Silva, F.A.; Aboy, A.L.; Bassani, V.L.; et al. Antioxidant activities and free radical scavenging potential of Bauhinia microstachya (Raddi) Macbr. (Caesalpinaceae) extracts linked to their polyphenol content. Biol. Pharm. Bull. 2007, 30, 1488–1496. [Google Scholar] [CrossRef] [Green Version]
  42. Amorozo, M.C.M. Uso e diversidade de plantas medicinais em Santo Antonio do Leverger, M.T. Brasil. Acta Bot. Bras. 2002, 16, 189–203. [Google Scholar] [CrossRef] [Green Version]
  43. Cunha, S.A.D.; Bortolotto, I.M. Etnobotânica de plantas medicinais no assentamento Monjolinho, município de Anastácio, Mato Grosso do Sul, Brasil. Acta Bot. Brasil. 2011, 25, 685–698. [Google Scholar] [CrossRef] [Green Version]
  44. Macedo, M.; Ferreira, A.R. Plantas hipoglicemiantes utilizadas por comunidades tradicionais na Bacia do Alto Paraguai e Vale do Guaporé, Mato Grosso-Brasil. Rev. Bras. Farmacogn. 2004, 14, 45–47. [Google Scholar] [CrossRef]
  45. Silva, M.A.B.; Melo, L.V.L.; Ribeiro, R.V.; Souza, J.P.M.; Lima, J.C.S.; Martins, D.T.O.; Silva, R.M. Levantamento etnobotânico de plantas utilizadas como anti-hiperlipidêmicas e anorexígenas pela população de Nova Xavantina-MT, Brasil. Rev. Bras. Farmacogn. 2010, 20, 549–562. [Google Scholar] [CrossRef] [Green Version]
  46. Pinto, A.A.D.C.; Maduro, C.B. Produtos e subprodutos da medicina popular comercializados na cidade de boa vista, Roraima. Acta Amazon. 2003, 33, 281–290. [Google Scholar] [CrossRef]
  47. Souza, B.V.C.; Araújo, R.S.R.M.; Silva, O.A.; Faustino, L.C.; Gonçalves, M.F.B.; Santos, M.L.; Souza, G.R.; Rocha, L.M.; Cardoso, M.L.S.; Nunes, L.C.C. Bauhinia forficata in the treatment of diabetes mellitus: A patent review. Expert Opin. Ther. Pat. 2018, 28, 129–138. [Google Scholar]
  48. SCImago Journal & Country Rank. Available online: https://www.scimagojr.com/index.php (accessed on 15 January 2021).
  49. Latindex. Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal. Available online: https://www.latindex.org/latindex/Solar/Busqueda (accessed on 29 January 2021).
  50. Neuhof, C.; Oliva, M.L.V.; Maybauer, D.; De Oliveira, C.; Sampaio, M.U.; Sampaio, C.A.M.; Neuhof, H.; Maybauer, M. Effect of plant Kunitz inhibitors from Bauhinia bauhinioides and Bauhinia rufa on pulmonary edema caused by activated neutrophils. Biol. Chem. 2003, 384, 939–944. [Google Scholar] [CrossRef]
  51. Oliveira, C.; Navarro-Xavier, R.A.; Anjos-Vallota, E.A.; Martins, J.O.; Silveira, V.L.F.; Gonçalves, L.R.C.; Araújo, M.S.; Motta, G.; Sannomiya, P.; Oliva, M.L.V. Effect of plant neutrophil elastase inhibitor on leucocyte migration, adhesion and cytokine release in inflammatory conditions. Br. J. Pharmacol. 2010, 161, 899–910. [Google Scholar] [CrossRef] [PubMed]
  52. Girão, D.K.F.B.; Cavada, B.S.; Pires, A.D.F.; Martins, T.V.; Franco, X.; Morais, C.M.; Nascimento, K.S.D.; Delatorre, P.; da Silva, H.C.; Nagano, C.S.; et al. The galactose-binding lectin isolated from Bauhinia bauhinioides Mart seeds inhibits neutrophil rolling and adhesion via primary cytokines. J. Mol. Recognit. 2015, 28, 285–292. [Google Scholar] [CrossRef]
  53. Almeida-Reis, R.; Theodoro-Junior, O.A.; Oliveira, B.T.M.; Oliva, L.V.; Toledo-Arruda, A.C.; Bonturi, C.R.; Brito, M.V.; Lopes, F.D.T.Q.S.; Prado, C.M.; Florencio, A.C.; et al. Plant proteinase inhibitor BbCI modulates lung inflammatory responses and mechanic and remodeling alterations induced by elastase in mice. BioMed. Res. Int. 2017, 1–13. [Google Scholar] [CrossRef] [Green Version]
  54. Martins-Olivera, B.T.; Almeida-Reis, R.; Theodoro-Júnior, O.A.; Oliva, L.V.; Santos Nunes, N.N.; Olivo, C.R.; Brito, M.V.; Prado, C.M.; Leick, E.A.; Arruda Martins, M.; et al. The plant-derived Bauhinia bauhinioides Kallikrein proteinase inhibitor (rBbKI) attenuates elastase-induced emphysema in mice. Mediat. Inflamm. 2016, 2016, 1–12. [Google Scholar] [CrossRef] [Green Version]
  55. Brito, M.V.; Oliveira, C.; Salu, B.R.; Andrade, S.A.; Malloy, P.M.; Sato, A.C.; Vicente, C.P.; Sampaio, M.; Maffei, F.H.A.; Oliva, M.L.V. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models. Thromb. Res. 2014, 133, 945–951. [Google Scholar] [CrossRef]
  56. Bilgin, M.; Neuhof, C.; Doerr, O.; Benscheid, U.; Andrade, S.S.; Most, A.; Abdallah, Y.; Parahuleva, M.; Guenduez, D.; Oliva, M.L.; et al. Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration. J. Physiol. Biochem. 2010, 66, 283–290. [Google Scholar] [CrossRef]
  57. Bilgin, M.; Burgazli, K.M.; Rafiq, A.; Mericliler, M.; Neuhof, C.; Oliva, M.L.; Parahuleva, M.; Soydan, N.; Doerr, O.; Abdallah, Y.; et al. Effect of Bauhinia bauhinioides kallikrein inhibitor on endothelial proliferation and intracellular calcium concentration. Eur. Rev. Med. Pharmacol. Sci. 2014, 18, 46–51. [Google Scholar] [PubMed]
  58. Nakahata, A.M.; Mayer, B.; Neth, P.; Hansen, D.; Sampaio, M.U.; Oliva, M.L.V. Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds. Planta Med. 2013, 79, 227–235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  59. Oliveira, D.; Santana, L.A.; Carmona, A.K.; Cezari, M.H.; Sampaio, M.U.; Sampaio, C.A.; Oliva, M.L.V. Structure of cruzipain/cruzain inhibitors isolated from Bauhinia bauhinioides seeds. Biol. Chem. 2001, 382, 847–852. [Google Scholar] [CrossRef] [PubMed]
  60. Araújo, A.P.U.; Hansen, D.; Vieira, D.F.; Oliveira, C.D.; Santana, L.A.; Beltramini, L.M.; Sampaio, C.A.M.; Sampaio, M.U.; Oliva, M.L.V. Kunitz-type Bauhinia bauhinioides inhibitors devoid of disulfide bridges: Isolation of the cDNAs, heterologous expression and structural studies. Biol. Chem. 2005, 386, 561–568. [Google Scholar] [CrossRef]
  61. Oliva, M.L.V.; Mendes, C.R.; Santomauro-Vaz, E.M.; Juliano, M.A.; Mentele, R.; Auerswald, E.A.; Sampaio, M.U.; Sampaio, C.A.M. Bauhinia bauhinioides plasma kallikrein inhibitor interaction with synthetic peptides and fluorogenic peptide substrates related to the reactive site sequence. Curr. Med. Chem. 2001, 8, 977–984. [Google Scholar] [CrossRef]
  62. Silva, A.M.A.; Silva, H.C.; Monteiro, A.O.; Lemos, T.L.G.; Souza, S.M.; Militão, G.C.G.; Santos, H.V.; Alves, P.B.; Romero, N.R.; Santiago, G.M.P. Chemical composition, larvicidal and cytotoxic activities of the leaf essential oil of Bauhinia cheilantha (Bong.) Steud. S. Afr. J. Bot. 2020, 131, 369–373. [Google Scholar] [CrossRef]
  63. Barbosa, P.B.B.M.; Oliveira, J.M.; Chagas, J.M.; Rabelo, L.M.A.; Medeiros, G.F.; Giodani, R.B.; Silva, E.A.; Uchôa, A.F.; Ximenes, M.F.F. Evaluation of seed extracts from plants found in the Caatinga biome for the control of Aedes aegypti. Parasitol. Res. 2014, 113, 3565–3580. [Google Scholar] [CrossRef]
  64. Luna, J.D.S.; DOS Santos, A.F.; de Lima, M.; de Omena, M.; de Mendonça, F.; Bieber, L.; Sant’Ana, A. A study of the larvicidal and molluscicidal activities of some medicinal plants from northeast Brazil. J. Ethnopharmacol. 2005, 97, 199–206. [Google Scholar] [CrossRef]
  65. Silva, M.C.C.; Santana, L.A.; Mentele, R.; Ferreira, R.S.; Miranda, A.; Silva-Lucca, R.A.; Sampaio, M.U.; Correia, M.T.S.; Oliva, M.L. Purification, primary structure and potential functions of a novel lectin from Bauhinia forficata seeds. Process Biochem. 2012, 47, 1049–1059. [Google Scholar] [CrossRef] [Green Version]
  66. Oliveira, C.Z.; Maiorano, V.A.; Marcussi, S.; Sant’Ana, C.D.; Januário, A.H.; Lourenço, M.V.; Sampaio, S.V.; França, S.C.; Pereira, S.P.; Soares, A.M. Anticoagulant and antifibrinogenolytic properties of the aqueous extract from Bauhinia forficata against snake venoms. J. Ethnopharmacol. 2005, 98, 213–216. [Google Scholar] [CrossRef]
  67. Anjos, P.J.C.; Pereira, P.R.; Moreira, I.J.A.; Serafini, M.R.; Araújo, A.A.S.; Silva, F.A.; Ramos, C.S.; Antoniolli, A.R.; Santos, M.R.V. Antihypertensive effect of Bauhinia forficata aqueous extract in rats. J. Pharmacol. Toxicol. 2013, 8, 82–89. [Google Scholar] [CrossRef] [Green Version]
  68. Souza, P.; Silva, L.M.; Boeing, T.; Somensi, L.B.; Cechinel-Zanchett, C.C.; Campos, A.; Krueger, C.M.A.; Bastos, J.K.; Cechinel-Filho, V.; Andrade, S.F. Influence of prostanoids in the diuretic and natriuretic effects of extracts and kaempferitrin from Bauhinia forficata link leaves in rats. Phytother. Res. 2017, 31, 1521–1528. [Google Scholar] [CrossRef] [PubMed]
  69. Fuentes Mardones, O.; Alarcón Enos, J. Bauhinia candicans improves the endothelium dependent relaxation in aortic rings of alloxan-diabetic rats. Bol. Latinoam. Caribe Plant. Med. Aromat. 2010, 9, 485–490. [Google Scholar]
  70. Cechinel-Zanchett, C.C.; Silva, R.C.M.V.A.F.; Tenfen, A.; Siebert, D.A.; Micke, G.; Vitali, L.; Cechinel-Filho, V.; Andrade, S.F.; Souza, P. Bauhinia forficata link, a Brazilian medicinal plant traditionally used to treat cardiovascular disorders, exerts endothelium-dependent and independent vasorelaxation in thoracic aorta of normotensive and hypertensive rats. J. Ethnopharmacol. 2019, 243, 112–118. [Google Scholar] [CrossRef] [PubMed]
  71. Alves, E.P.; de F, L.R.; de Almeida, C.M.; Freires, I.A.; Rosalen, P.L.; Ruiz, A.L.; Granville-Garcia, A.F.; Godoy, G.P.; Pereira, J.V.; de Brito Costa, E.M. Antimicrobial and antiproliferative activity of Bauhinia forficata Link and Cnidoscolus quercifolius extracts commonly used in folk medicine. J. Contemp. Dent. Pract. 2017, 18, 635–640. [Google Scholar]
  72. Ferreira-Filho, J.C.C.; Marre, A.T.O.; Almeida, J.S.S.; Lobo, L.A.; Farah, A.; Valença, A.M.G.; Fonseca-Gonçalves, A. Treatment of dental biofilm with a tincture of Bauhinia forficata leaves: An ex-vivo study. Nat. Prod. Res. 2019, 33, 3432–3435. [Google Scholar] [CrossRef]
  73. Ferreira-Filho, J.C.C.; Marre, A.T.O.; Almeida, J.S.S.; Lobo, L.A.; Farah, A.; Romanos, M.T.V.; Maia, L.C.; Valença, A.M.G.; Fonseca-Gonçalves, A. Therapeutic Potential of Bauhinia forficata Link in dental biofilm treatment. J. Med. Food 2020, 23, 998–1005. [Google Scholar] [CrossRef]
  74. Sousa, J.N.; Oliveira, A.B.M.; Ferreira e Silva, A.K.; Sousa, L.M.S.; Rocha, M.C.F.; Siqueira Júnior, J.P.; Kaatz, G.W.; Almeida, J.R.G.S.; Souza, J.S.N.; Barreto, H.M. Modulation of the resistance to norfloxacin in Staphylococcus aureus by Bauhinia forficata link. Nat. Prod. Res. 2021, 35, 681–685. [Google Scholar] [CrossRef]
  75. Sousa, E.; Zanatta, L.; Seifriz, I.; Creczynski-Pasa, T.B.; Pizzolatti, M.G.; Szpoganicz, B.; Silva, F.R.M.B. Hypoglycemic effect and antioxidant potential of kaempferol-3, 7-O-(α)-dirhamnoside from Bauhinia forficata leaves. J. Nat. Prod. 2004, 67, 829–832. [Google Scholar] [CrossRef]
  76. Khalil, N.M.; Pepato, M.T.; Brunetti, I.L. Free radical scavenging profile and myeloperoxidase inhibition of extracts from antidiabetic plants: Bauhinia forficata and Cissus sicyoides. Biol. Res. 2008, 41, 165–171. [Google Scholar] [CrossRef] [Green Version]
  77. Volpato, G.T.; Damasceno, D.C.; Rudge, M.V.C.; Padovani, C.R.; Calderon, I.D.M.P. Effect of Bauhinia forficata aqueous extract on the maternal-fetal outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats. J. Ethnopharmacol. 2008, 116, 131–137. [Google Scholar] [CrossRef] [PubMed]
  78. Souza, C.R.F.; Georgetti, S.R.; Salvador, M.J.; Fonseca, M.J.V.; Oliveira, W.P. Antioxidant activity and physical-chemical properties of spray and spouted bed dried extracts of Bauhinia forficata. Braz. J. Pharm. Sci. 2009, 45, 209–218. [Google Scholar] [CrossRef] [Green Version]
  79. Ferreres, F.; Gil-Izquierdo, A.; Vinholes, J.; Silva, S.T.; Valentão, P.; Andrade, P.B. Bauhinia forficata Link authenticity using flavonoids profile: Relation with their biological properties. Food Chem. 2012, 134, 894–904. [Google Scholar] [CrossRef]
  80. Marques, G.S.; Lyra, M.A.M.; Peixoto, M.S.; Monteiro, R.P.M.; Leão, W.F.; Xavier, H.S.; Soares, L.A.L.; Neto, P.J.R. Caracterização fitoquímica e físico-química das folhas de Bauhinia forficata Link coletada em duas regiões brasileiras. Rev. Ciênc. Farm. Básica Apl. 2012, 33, 57–62. [Google Scholar]
  81. Peroza, L.R.; Busanello, A.; Leal, C.Q.; Röpke, J.; Boligon, A.A.; Meinerz, D.; Libardoni, M.; Athayde, M.L.; Fachinetto, R. Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro. Neurochem. Res. 2013, 38, 789–796. [Google Scholar] [CrossRef]
  82. Salgueiro, A.C.; Leal, C.Q.; Bianchini, M.C.; Prado, I.O.; Mendez, A.S.; Puntel, R.L.; Folmer, V.; Soares, F.A.; Ávila, D.S.; Puntel, G.O. The influence of Bauhinia forficata Link subsp. pruinosa tea on lipid peroxidation and non-protein SH groups in human erythrocytes exposed to high glucose concentrations. J. Ethnopharmacol. 2013, 148, 81–87. [Google Scholar] [CrossRef]
  83. Ecker, A.; Vieira, F.A.; Prestes, A.; Dos Santos, M.M.; Ramos, A.; Ferreira, R.D.; De Macedo, G.T.; Klimaczewski, C.V.; Seeger, R.; Da Rocha, J.B.T.; et al. Effect of Syzygium cumini and Bauhinia forficata aqueous-leaf extracts on oxidative and mitochondrial parameters in vitro. EXCLI J. 2015, 14, 1219–1231. [Google Scholar] [PubMed]
  84. Farag, M.A.; Sakna, S.T.; El-fiky, N.M.; Shabana, M.M.; Wessjohann, L.A. Phytochemical, antioxidant and antidiabetic evaluation of eight Bauhinia L. species from Egypt using UHPLC-PDA-qTOF-MS and chemometrics. Phytochemistry 2015, 119, 41–50. [Google Scholar] [CrossRef]
  85. Salgueiro, A.C.F.; Folmer, V.; Silva, M.P.; Mendez, A.S.L.; Zemolin, A.P.P.; Posser, T.; Franco, J.L.; Puntel, R.L.; Puntel, G.O. Effects of Bauhinia forficata tea on oxidative stress and liver damage in diabetic mice. Oxid. Med. Cell. Longev. 2016, 2016, 1–9. [Google Scholar] [CrossRef] [Green Version]
  86. Ecker, A.; Gonzaga, T.K.S.N.; Seeger, R.L.; Santos, M.M.; Loreto, J.S.; Boligon, A.A.; Meinerz, D.F.; Lugokenski, T.H.; Rocha, J.B.T.; Barbosa, N.V. High-sucrose diet induces diabetic-like phenotypes and oxidative stress in Drosophila melanogaster: Protective role of Syzygium cumini and Bauhinia forficata. Biomed. Pharmacother. 2017, 89, 605–616. [Google Scholar] [CrossRef]
  87. Franco, R.R.; Carvalho, D.S.; Moura, F.B.R.; Justino, A.B.; Silva, H.C.G.; Peixoto, L.G.; Espindola, F.S. Antioxidant and anti-glycation capacities of some medicinal plants and their potential inhibitory against digestive enzymes related to type 2 diabetes mellitus. J. Ethnopharmacol. 2018, 215, 140–146. [Google Scholar] [CrossRef] [PubMed]
  88. Pinafo, M.S.; Benedetti, P.R.; Gaiotte, L.B.; Costa, F.G.; Schoffen, J.P.F.; Fernandes, G.S.A.; Chuffa, L.G.A.; Seiva, F.R.F. Effects of Bauhinia forficata on glycaemia, lipid profile, hepatic glycogen content and oxidative stress in rats exposed to Bisphenol A. Toxicol. Rep. 2019, 6, 244–252. [Google Scholar] [CrossRef] [PubMed]
  89. Sampaio, C.F.; Lucchetta, N.R.; Punhagui, A.P.F.; Banedetti, P.R.; Arakawa, N.S.; Seiva, F.R.F.; Fernandes, G.S.A. Alcohol extract of Bauhinia forficata link reduces lipid peroxidation in the testis and epididymis of adult Wistar rats. Microsc. Res. Tech. 2019, 82, 345–351. [Google Scholar] [CrossRef]
  90. Franco, R.R.; Alves, V.H.M.; Zabisky, L.F.R.; Justino, A.B.; Martins, M.M.; Saraiva, A.L.; Goulart, L.R.; Espindola, F.S. Antidiabetic potential of Bauhinia forficata Link leaves: A non-cytotoxic source of lipase and glycoside hydrolases inhibitors and molecules with antioxidant and antiglycation properties. Biomed. Pharmacother. 2020, 123, 109798. [Google Scholar] [CrossRef]
  91. Pinto, L.S.; Cardoso, G.; Kremer, F.S.; Woloski, R.D.S.; Dellagostin, O.A.; Campos, V.F. Heterologous expression and characterization of a new galactose-binding lectin from Bauhinia forficata with antiproliferative activity. Int. J. Biol. Macromol. 2019, 128, 877–884. [Google Scholar] [CrossRef]
  92. Lim, H.; Kim, M.K.; Lim, Y.; Cho, Y.H.; Lee, C.H. Inhibition of cell-cycle progression in HeLa cells by HY52, a novel cyclin-dependent kinase inhibitor isolated from Bauhinia forficata. Cancer Lett. 2006, 233, 89–97. [Google Scholar] [CrossRef]
  93. Lim, H.; Lim, Y.; Cho, Y.H.; Lee, C.H. Induction of apoptosis in the HepG2 cells by HY53, a novel natural compound isolated from Bauhinia forficata. J. Microbiol. Biotechnol. 2006, 16, 1262–1268. [Google Scholar]
  94. Cechinel-Zanchett, C.C.; Boeing, T.; Somensi, L.B.; Steimbach, V.M.B.; Campos, A.; Krueger, C.D.M.A.; Schultz, C.; Sant’Ana, D.D.M.G.; Cechinel-Filho, V.; da Silva, L.M.; et al. Flavonoid-rich fraction of Bauhinia forficata Link leaves prevents the intestinal toxic effects of irinotecan chemotherapy in IEC-6 cells and in mice. Phytother. Res. 2019, 33, 90–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Lubkowski, J.; Durbin, S.V.; Silva, M.C.; Farnsworth, D.; Gildersleeve, J.C.; Oliva, M.L.; Wlodawer, A. Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth. FEBS J. 2017, 284, 429–450. [Google Scholar] [CrossRef] [PubMed]
  96. Silva, M.C.C.; Paula, C.A.; Ferreira, J.G.; Paredes-Gamero, E.J.; Vaz, A.M.; Sampaio, M.U.; Correia, M.T.S.; Oliva, M.L.V. Bauhinia forficata lectin (BfL) induces cell death and inhibits integrin-mediated adhesion on MCF7 human breast cancer cells. Biochim. Biophys. Acta Gen. Subj. 2014, 1840, 2262–2271. [Google Scholar] [CrossRef]
  97. Düsman, E.; Almeida, I.V.; Coelho, A.C.; Balbi, T.J.; Tonin, L.T.D.; Vicentini, V.E.P. Antimutagenic effect of medicinal plants Achillea millefolium and Bauhinia forficata in vivo. Evid. Based Complement. Alternat. Med. 2013, 2013, 1–6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  98. Rozza, A.L.; Cesar, D.A.S.; Pieroni, L.G.; Saldanha, L.L.; Dokkedal, A.L.; De-Faria, F.M.; Souza-Brito, A.R.M.; Vilegas, W.; Takahira, R.K.; Pellizzon, C.H. Antiulcerogenic activity and toxicity of Bauhinia holophylla hydroalcoholic extract. J. Evid.-Based. Complement. Altern. Med. 2015, 2015, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  99. Ribeiro, D.L.; Cilião, H.L.; Specian, A.F.L.; Serpeloni, J.M.; De Oliveira, M.T.; Varanda, E.A.; Vilegas, W.; Saldanha, L.L.; Martínez-López, W.; Dokkedal, A.L.; et al. Phytochemical study and evaluation of cytotoxicity, mutagenicity, cell cycle kinetics and gene expression of Bauhinia holophylla (Bong.) Steud. in HepG2 cells in vitro. Cytotechnology 2018, 70, 713–728. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  100. Mazzeo, G.C.C.; Silva, M.P.O.; Guimarães, L.L.; Brito, A.R.M.S.; Toma, W. Evaluation of anti-ulcerogenic activity in an aqueous extract obtained from Bauhinia forficata leaves. Rev. Cienc. Farm. Basica Apl. 2015, 36, 21–26. [Google Scholar]
  101. Dos Santos, M.; Teixeira, T.R.; Santos, F.R.D.S.; Lima, W.G.; Ferraz, A.C.; Silva, N.L.; Leite, F.J.; Siqueira, J.M.; Luyten, W.; de Castro, A.H.F.; et al. Bauhinia holophylla (Bong.) Steud. leaves-derived extracts as potent anti-dengue serotype 2. Nat. Prod. Res. 2019, 35, 2804–2809. [Google Scholar] [CrossRef]
  102. Gadotti, V.M.; Santos, A.R.S.; Meyre-Silva, C.; Schmeling, L.O.; Machado, C.; Liz, F.H.; Filho, V.C. Antinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leaves. J. Pharm. Pharmacol. 2005, 57, 1345–1351. [Google Scholar] [CrossRef]
  103. Ramos, S.A.; Remor, C.; Emendörfer, F.; Meyre-Silva, C.; Cechinel Filho, V.; Santos, A.R.S.; Cardozo, A.M. Antispasmodic effects of Bauhinia microstachya on isolated smooth muscle. Pharm. Biol. 2005, 43, 467–470. [Google Scholar] [CrossRef]
  104. Menezes, P.R.; Schwarz, E.A.; Santos, C.A. In vitro antioxidant activity of species collected in Paraná. Fitoterapia. 2004, 75, 398–400. [Google Scholar] [CrossRef]
  105. Bianco, E.M.; Santos, C.A.M. Propriedades antioxidantes de folhas e caules de Bauhinia microstachya (Raddi) JF Macbr. R. Bras. Bioci. 2010, 8, 238–241. [Google Scholar]
  106. Mansur, M.C.P.P.R.; Leitao, S.G.; Lima, L.M.T.R.; Ricci-Junior, E.; Souza, G.R.; Barbi, N.S.; Martins, T.S.; Dellamora-Ortiz, G.M.; Rodrigo, R.T.L.; Vieira, R.C.; et al. Evaluation of the antioxidant and phototoxic potentials of Bauhinia microstachya var. massambabensis Vaz leaf extracts. Lat. Am. J. Pharm. 2012, 31, 200–206. [Google Scholar]
  107. Mansur, M.C.; Leitão, S.G.; Cerqueira-Coutinho, C.; Vermelho, A.B.; Silva, R.S.; Presgrave, O.A.; Leitão, Á.A.; Leitão, G.G.; Ricci-Júnior, E.; Santos, E.P. In vitro and in vivo evaluation of efficacy and safety of photoprotective formulations containing antioxidant extracts. Rev. Bras. Farmacogn. 2016, 26, 251–258. [Google Scholar] [CrossRef] [Green Version]
  108. Correia, A.F.; Silveira, D.; Fonseca-Bazzo, Y.M.; Magalhães, P.O.; Fagg, C.W.; Silva, E.C.; Gomes, S.M.; Gandolfi, L.; Pratesi, R.; Nóbrega, Y.K.M. Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species. BMC Complement. Altern. Med. 2016, 16, 1–9. [Google Scholar] [CrossRef] [PubMed]
  109. Ferreira, J.G.; Diniz, P.M.M.; Paula, C.A.A.; Lobo, Y.A.; Paredes-Gamero, E.J.; Paschoalin, T.; Nogueira-Pedro, A.; Maza, P.K.; Toledo, M.S.; Suzuki, E.; et al. The impaired viability of prostate cancer cell lines by the recombinant plant kallikrein inhibitor. J. Biol. Chem. 2013, 288, 13641–13654. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  110. Nakahata, A.M.; Bueno, N.R.; Rocha, H.A.; Franco, C.R.; Chammas, R.; Nakaie, C.R.; Jasiulionis, M.; Nader, H.B.; Santana, L.A.; Sampaio, M.U.; et al. Structural and inhibitory properties of a plant proteinase inhibitor containing the RGD motif. Int. J. Biol. Macromol. 2006, 40, 22–29. [Google Scholar] [CrossRef] [PubMed]
  111. Silveira, D.; Faitanin, R.D.; Gomes, S.M.; Fagg, C.W.; Fonseca-Bazzo, Y.M.; Magalhães, P.O.; Jamal, C.M. Thrombolytic activity evaluation of extracts from Fabaceae species Bauhinia variegata, B. rufa, and Stryphnodendron adstringens. Pharmacol. Online 2016, 3, 56–60. [Google Scholar]
  112. Neto, J.A.R.; Teixeira, J.L.; Alves, S.N.; Júnior, P.J. Avaliação dos efeitos da cafeína anidra e de diferentes extratos de “pata de vaca” (Bauhinia rufa) e café arábica (Coffea arabica) em larvas de Culex quinquefasciatus. Rev. Eletrônica Biol. 2014, 6, 175–183. [Google Scholar]
  113. Lacerda, G.M.; Monteiro, A.B.; Tintino, S.R.; Delmondes, G.A.; Fernandes, C.N.; Lemos, I.C.S.; Nascimento, E.P.; Carvalho, T.B.; Coutinho, H.D.M.; Menezes, I.R.A.; et al. Atividade moduladora sobre antibióticos pelo extrato aquoso das folhas de Bauhinia ungulata L. Rev. Cubana Plant. Med. 2016, 21. [Google Scholar]
  114. Medeiros, S.R.; Filho, A.A.M.; Costa, H.N.R.; Silva, F.S.; Santos, R.C.; Takahashi, J.A.; Ferraz, V.P.; Melo, A.C.G.R.; Ribeiro, P.R.E.; Laranjeira, A.G.A.; et al. Chemical profile, antimicrobial activity, toxicity on Artemia salina and anti-acetylcholinesterase enzyme essential oil from Bauhinia ungulata L.(Fabaceae) leaves. J. Med. Plant Res. 2016, 10, 442–449. [Google Scholar]
  115. Paula, C.D.S.; Canteli, V.C.D.; Hirota, B.C.K.; Campos, R.; Oliveira, V.B.D.; Kalegari, M.; Silva, C.B.; Silva, G.M.; Miguel, O.G.; Miguel, M.D. Potencial antioxidante in vitro das folhas da Bauhinia ungulata L. Rev. Cienc. Farm. Basica Apl. 2014, 35, 217–222. [Google Scholar]
  116. Rodrigues, R.O.; Yaochite, J.N.U.; Braga, M.A.; Sousa, A.R.; Sasahara, G.L.; Fonseca, S.G.C.; Araújo, T.D.V.; Santiago, G.M.P.; Sousa, L.M.; Carvalho, J.L.; et al. Antioxidant and antiinflammatory activities of Bauhinia ungulata L. (Fabaceae) on LPS-Stimulated RAW 264.7 cells. Pharmacogn. J. 2019, 11, 37–42. [Google Scholar] [CrossRef] [Green Version]
  117. Silva, H.C.; Pinto, L.D.S.; Teixeira, E.H.; Nascimento, K.S.; Cavada, B.S.; Silva, A.L.C. BUL: A novel lectin from Bauhinia ungulata L. seeds with fungistatic and antiproliferative activities. Process Biochem. 2014, 49, 203–209. [Google Scholar] [CrossRef] [Green Version]
  118. Sousa, L.M.; Carvalho, J.L.; Gois, R.W.; Silva, H.C.; Santiago, G.M.P.; Lemos, T.L.G.; Arriaga, A.M.C.; Alves, P.B.; Matos, I.L.; Militão, G.C.G.; et al. Chemical composition, larvicidal and cytotoxic activities of the essential oils from two Bauhinia species. Rec. Nat. Prod. 2016, 10, 341–348. [Google Scholar]
  119. Sousa, L.M.; Carvalho, J.L.; Silva, H.C.; Lemos, T.L.; Arriaga, A.M.; Braz-Filho, R.; Militão, G.C.; Silva, T.D.; Ribeiro, P.R.; Santiago, G.M. New Cytotoxic Bibenzyl and other constituents from Bauhinia ungulata L. (Fabaceae). Chem. Biodivers. 2016, 13, 1630–1635. [Google Scholar] [CrossRef]
  120. Rodrigues, R.O.; Yaochite, J.N.U.; Sasahara, G.L.; Albuquerque, A.A.; Fonseca, S.G.C.; Araújo, T.D.V.; Santiago, G.M.P.; Sousa, L.M.; Carvalho, J.L.; Alves, A.P.N.N.; et al. Antioxidant, anti-inflammatory and healing potential of ethyl acetate fraction of Bauhinia ungulata L. (Fabaceae) on in vitro and in vivo wound model. Mol. Biol. Rep. 2020, 47, 2845–2859. [Google Scholar] [CrossRef]
  121. Santos, K.M.; Gonçalves, P.S.; Paiva, M.J.; Lacerda, G.A. Acetylcholinesterase inhibition starting from extracts of Bauhinia variegata L.; Bauhinia variegata var. candida (Aiton) Buch.-Ham., and Bauhinia ungulata L. Rev. Soc. Bras. Med. Trop. 2011, 44, 781–783. [Google Scholar] [CrossRef]
  122. Santos, K.M.; Nunes, D.A.F.; Gomes, I.N.F.; Silva, S.L.; Ribeiro, R.I.M.A. Inhibition of gelatinase activity of MMP-2 and MMP-9 by extracts of Bauhinia ungulata L. Biosci. J. 2015, 31, 584–590. [Google Scholar] [CrossRef] [Green Version]
  123. Oliva, M.L.V.; Andrade, S.A.; Juliano, M.A.; Sallai, R.C.; Torquato, R.J.; Sampaio, M.U.; Pott, V.J.; Sampaio, C.A.M. Kinetic characterization of factor Xa binding using a quenched fluorescent substrate based on the reactive site of factor Xa inhibitor from Bauhinia ungulata seeds. Curr. Med. Chem. 2003, 10, 1085–1093. [Google Scholar] [CrossRef]
  124. Soares, J.C.M.; Costa, S.T.D.; Cecim, M. Níveis glicêmicos e de colesterol em ratos com diabetes mellitus aloxano induzido, tratados com infusão de Bauhinia candicans ou Syzygium jambolanum. Ciência Rural 2000, 30, 113–118. [Google Scholar] [CrossRef]
  125. Pepato, M.T.; Keller, E.H.; Baviera, A.M.; Kettelhut, I.C.; Vendramini, R.C.; Brunetti, I.L. Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats. J. Ethnopharmacol. 2002, 81, 191–197. [Google Scholar] [CrossRef]
  126. Silva, F.R.M.B.; Szpoganicz, B.; Pizzolatti, M.G.; Willrich, M.A.V.; Sousa, E. Acute effect of Bauhinia forficata on serum glucose levels in normal and alloxan-induced diabetic rats. J. Ethnopharmacol. 2002, 83, 33–37. [Google Scholar] [CrossRef]
  127. Damasceno, D.; Volpato, G.; Calderon, I.D.M.P.; Aguilar, R.; Rudge, M.C. Effect of Bauhinia forficata extract in diabetic pregnant rats: Maternal repercussions. Phytomedicine 2004, 11, 196–201. [Google Scholar] [CrossRef]
  128. Fuentes, O.; Arancibia-Avila, P.; Alarcón, J. Hypoglycemic activity of Bauhinia candicans in diabetic induced rabbits. Fitoterapia 2004, 75, 527–532. [Google Scholar] [CrossRef] [PubMed]
  129. Jorge, A.P.; Horst, H.; Sousa, E.; Pizzolatti, M.G.; Silva, F.R.M.B. Insulinomimetic effects of kaempferitrin on glycaemia and on 14 C-glucose uptake in rat soleus muscle. Chem.-Biol. Interact. 2004, 149, 89–96. [Google Scholar] [CrossRef]
  130. Lino, C.S.; Diógenes, J.P.L.; Pereira, B.A.; Faria, R.A.P.G.; Neto, M.A.; Alves, R.S.; Queiroz, M.G.R.; Sousa, F.C.F.; Viana, G.S.B. Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats. Biol. Pharm. Bull. 2004, 27, 125–127. [Google Scholar] [CrossRef] [Green Version]
  131. Vasconcelos, F.; Sampaio, S.V.; Garófalo, M.A.; Guimarães, L.F.; Giglio, J.R.; Arantes, E.C. Insulin-like effects of Bauhinia forficata aqueous extract upon Tityus serrulatus scorpion envenoming. J. Ethnopharmacol. 2004, 95, 385–392. [Google Scholar] [CrossRef] [PubMed]
  132. Menezes, F.D.S.; Minto, A.B.M.; Ruela, H.S.; Kuster, R.M.; Sheridan, H.; Frankish, N. Hypoglycemic activity of two Brazilian Bauhinia species: Bauhinia forficata L. and Bauhinia monandra Kurz. Rev. Bras. Farmacogn. 2007, 17, 8–13. [Google Scholar] [CrossRef] [Green Version]
  133. Cunha, A.M.D.; Menon, S.; Menon, R.; Couto, A.G.; Bürger, C.; Biavatti, M.W. Hypoglycemic activity of dried extracts of Bauhinia forficata Link. Phytomedicine 2010, 17, 37–41. [Google Scholar] [CrossRef] [PubMed]
  134. Pepato, M.T.; Conceição, C.Q.; Gutierres, V.O.; Vendramini, R.C.; Souza, C.R.F.; Oliveira, W.P.; Brunetti, I.L. Evaluation of the spouted bed dried leaf extract of Bauhinia forficata for the treatment of experimental diabetes in rats. Afr. J. Biotechnol. 2010, 9, 7157–7164. [Google Scholar]
  135. Curcio, S.A.; Stefan, L.F.; Randi, B.A.; Dias, M.A.; da Silva, R.E.; Caldeira, E.J. Hypoglycemic effects of an aqueous extract of Bauhinia forficata on the salivary glands of diabetic mice. Pak. J. Pharm. Sci. 2012, 25, 493–499. [Google Scholar]
  136. Fuentes, O.; Alarcón, J. Bauhinia candicans stimulation of glucose uptake in isolated gastric glands of normal and diabetic rabbits. Fitoterapia 2006, 77, 271–275. [Google Scholar] [CrossRef]
  137. Cazarolli, L.H.; Pereira, D.F.; Kappel, V.D.; Folador, P.; Figueiredo, M.S.R.B.; Pizzolatti, M.G.; Silva, F.R.M.B. Insulin signaling: A potential signaling pathway for the stimulatory effect of kaempferitrin on glucose uptake in skeletal muscle. Eur. J. Pharmacol. 2013, 712, 1–7. [Google Scholar] [CrossRef] [PubMed]
  138. Pozzobon, A.; Rempel, C.; Hoerlle, J.; Strohschoen, A.G.; Bosco, S.M.; Carreno, I. Avaliação do efeito da Bauhinia forficata no perfil glicêmico e verificação dos níveis séricos do cortisol de portadores de diabetes mellitus tipo 2, usuários de unidades básicas de saúde no vale do taquari, RS. Rev. Cad. Pedagógico 2012, 9, 9–23. [Google Scholar]
  139. Toloza-Zambrano, P.; Avello, M.; Fernández, P. Determinación de rutina y trigonelina en extractos de hojas de Bauhinia forficata subsp. pruinosa y evaluación del efecto hipoglicemiante en humanos. Bol. Latinoam. Caribe Plant. Med. Aromat. 2015, 14, 21–32. [Google Scholar]
  140. Mariángel, P.C.; Lorca, M.A.; Leon, F.M.; Rocca, P.F.; Zapata, L.V.; Navarrete, E.P. Effects of Bauhinia forficata Link tea on lipid profile in diabetic patients. J. Med. Food 2019, 22, 321–323. [Google Scholar] [CrossRef]
  141. Pinheiro, M.S.; Rodrigues, L.S.; Neto, L.S.; Moraes-Souza, R.Q.; Soares, T.S.; Americo, M.F.; Campos, K.E.; Damasceno, D.B.; Volpato, G.T. Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats. An. Acad. Bras. Ciênc. 2017, 89, 263–272. [Google Scholar] [CrossRef]
  142. Camaforte, N.A.P.; Saldanha, L.L.; Vareda, P.M.P.; Rezende-Neto, J.M.; Senger, M.R.; Delgado, A.Q.; Morgan, H.J.N.; Violato, N.M.; Pieroni, L.G.; Dokkedal, A.L.; et al. Hypoglycaemic activity of Bauhinia holophylla through GSK3-β inhibition and glycogenesis activation. Pharm. Biol. 2019, 57, 269–279. [Google Scholar] [CrossRef] [Green Version]
  143. Sobrinho, T.J.S.P.; Silva, C.H.T.P.; Nascimento, J.E.; Monteiro, J.M.; Albuquerque, U.P.; Amorim, E.L.C. Validação de metodologia espectrofotométrica para quantificação dos flavonóides de Bauhinia cheilantha (Bongard) Steudel. Rev. Bras. Cienc. Farm. 2008, 44, 683–689. [Google Scholar] [CrossRef] [Green Version]
  144. Silva, K.L.D.; Biavatti, M.W.; Leite, S.N.; Yunes, R.A.; Monache, F.D.; Filho, V.C. Phytochemical and pharmacognostic investigation of Bauhinia forficata Link (Leguminosae). Z. Naturforsch. 2000, 55, 478–480. [Google Scholar] [CrossRef]
  145. Pizzolatti, M.G.; Cunha, A.J.; Szpoganicz, B. Flavonoid glycosides from leaves and flowers of Bauhinia forficata (Leguminosae). Quim. Nova 2003, 26, 466–469. [Google Scholar] [CrossRef] [Green Version]
  146. Duarte-Almeida, J.M.; Negri, G.; Salatino, A. Volatile oils in leaves of Bauhinia (Fabaceae Caesalpinioideae). Biochem. Syst. Ecol. 2004, 32, 747–753. [Google Scholar] [CrossRef]
  147. Pinheiro, T.S.; Johansson, L.A.; Pizzolatti, M.G.; Biavatti, M.W. Comparative assessment of kaempferitrin from medicinal extracts of Bauhinia forficata Link. J. Pharm. Biomed. Anal. 2006, 41, 431–436. [Google Scholar] [CrossRef] [PubMed]
  148. Sartorilli, P.; Correa, D.S. Constituents of essential oil from Bauhinia forficata Link. J. Essent. Oil Res. 2007, 19, 468–469. [Google Scholar] [CrossRef]
  149. Sayago, C.T.M.; Camargo, V.B.; Barbosa, F.; Gularte, C.; Pereira, G.; Miotto, S.; Cechinel Filho, V.; Puntel, R.L.; Folmer, V.; Mendez, A. Chemical composition and in vitro antioxidant activity of hydro-ethanolic extracts from Bauhinia forficata subsp. pruinosa and B. variegata. Acta Biol. Hung. 2013, 64, 21–33. [Google Scholar] [CrossRef]
  150. Farias, L.D.S.; Mendez, A.S. LC/ESI-MS method applied to characterization of flavonoids glycosides in Bauhinia forficata subsp. pruinosa. Quim. Nova. 2014, 37, 483–486. [Google Scholar] [CrossRef]
  151. Santos, M.; Fortunato, R.H.; Spotorno, V.G. Analysis of flavonoid glycosides with potential medicinal properties on Bauhinia uruguayensis and Bauhinia forficata subspecies pruinosa. Nat. Prod. Res. 2019, 33, 2574–2578. [Google Scholar] [CrossRef] [PubMed]
  152. Bianco, E.M.; Santos, C.A.M. Substances isolated from Bauhinia microstachya (Raddi) Macbr. (Caesalpiniaceae) leaves. Rev. Bras. Farmacogn. 2003, 13, 93–99. [Google Scholar] [CrossRef]
  153. Neto, M.M.; Neto, M.A.; Filho, R.B.; Lima, M.A.S.; Silveira, E.R. Flavonoids and alkaloids from leaves of Bauhinia ungulata L. Biochem. Syst. Ecol. 2008, 36, 227–229. [Google Scholar] [CrossRef]
  154. Gramosa, N.V.; Freitas, J.V.B.; Neto, M.N.L.; Silveira, E.R.; Nunes, E.P. Volatile components of the essential oil from Bauhinia ungulata L. J. Essent. Oil Res. 2009, 21, 495–496. [Google Scholar] [CrossRef]
  155. Maritim, A.C.; Sanders, R.A.; Watkins, J.B., III. Diabetes, oxidative stress, and antioxidants: A review. J. Biochem. Mol. Toxicol. 2003, 17, 24–38. [Google Scholar] [CrossRef]
  156. Pisoschi, A.M.; Pop, A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur. J. Med. Chem. 2015, 97, 55–74. [Google Scholar] [CrossRef]
  157. Pedrete, T.A.; Hauser-Davis, R.A.; Moreira, J.C. Proteomic characterization of medicinal plants used in the treatment of diabetes. Int. J. Biol. Macromol. 2019, 140, 294–302. [Google Scholar] [CrossRef] [PubMed]
  158. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2014, 37 (Suppl. S1), S81–S90. [Google Scholar] [CrossRef] [PubMed]
  159. Prasad, C.V.; Mohan, S.S.; Banerji, A.; Gopalakrishnapillai, A. Kaempferitrin inhibits GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 2009, 380, 39–43. [Google Scholar] [CrossRef]
  160. Silva, D.; Casanova, L.M.; Marcondes, M.C.; Espindola-Netto, J.M.; Paixão, L.P.; Melo, G.O.; Zancan, P.; Sola-Penna, M.; Costa, S.S. Antidiabetic activity of Sedum dendroideum: Metabolic enzymes as putative targets for the bioactive flavonoid kaempferitrin. IUBMB life. 2014, 66, 361–370. [Google Scholar] [CrossRef]
  161. Tostes, J.B.; Siani, A.C.; Monteiro, S.S.; Melo, V.F.; Costa, J.O.; Valente, L.M.M. Seasonal flavonoid profile and kaempferitrin content in the leaf extracts of Bauhinia forficata subspecies forficata from two locations in southeastern Brazil. Am. J. Plant Sci. 2019, 10, 208–220. [Google Scholar] [CrossRef] [Green Version]
  162. Sobrinho, T.J.S.P.; Cardoso, K.D.; Gomes, T.D.L.; Albuquerque, U.P.; Amorim, E.L. Análise da pluviosidade e do efeito de borda sobre os teores de flavonóides em Bauhinia cheilantha (Bong.) Steud. Fabaceae. Rev. Bras. Farmacogn. 2009, 19, 740–745. [Google Scholar] [CrossRef] [Green Version]
  163. Martí, A.; Tapiz, C. Modelos murinos para el estudio de la diabetes tipo 2: Una revisión sistemática. Rev. ALAD 2019, 9, 165–178. [Google Scholar] [CrossRef]
  164. Sah, S.P.; Singh, B.; Choudhary, S.; Kumar, A. Animal models of insulin resistance: A review. Pharmacol. Rep. 2016, 68, 1165–1177. [Google Scholar] [CrossRef]
  165. Oliva, M.L.V.; Sampaio, M.U. Bauhinia Kunitz-type proteinase inhibitors: Structural characteristics and biological properties. Biol. Chem. 2008, 389, 1007–1013. [Google Scholar] [CrossRef]
  166. Oliva, M.L.V.; Sampaio, M.U. Action of plant proteinase inhibitors on enzymes of physiopathological importance. An. Acad. Bras. Ciênc. 2009, 81, 615–621. [Google Scholar] [CrossRef] [Green Version]
  167. Oliva, M.L.V.; Ferreira, R.S.; Ferreira, J.G.; Paula, C.A.A.; Salas, C.E.; Sampaio, M.U. Structural and functional properties of kunitz proteinase inhibitors from leguminosae: A mini review. Curr. Protein Pept. Sci. 2011, 12, 348–357. [Google Scholar] [CrossRef] [PubMed]
  168. Srikanth, S.; Chen, Z. Plant protease inhibitors in therapeutics-focus on cancer therapy. Front. Pharmacol. 2016, 7, 1–19. [Google Scholar] [CrossRef] [PubMed]
  169. Cagliari, R.; Kremer, F.S.; Pinto, L.S. Bauhinia lectins: Biochemical properties and biotechnological applications. Int. J. Biol. Macromol. 2018, 119, 811–820. [Google Scholar] [CrossRef] [PubMed]
  170. Simões, R.C.; Almeida, S. Estudo fitoquímico de Bauhinia forficata (Fabaceae). Biota Amaz. 2015, 5, 27–31. [Google Scholar] [CrossRef]
  171. Debenedetti, S.L.; Miño, J.; Rojo, A.; Acevedo, M.C.D. Ensayo del efecto diurético de los extractos acuosos de Amaranthus muricatus (Moquin) Gill. Ex Hicken, Bauhinia candicans Benth. y Smilax campestris Griseb. Acta Farm. Bonaerense. 2000, 19, 17–20. [Google Scholar]
  172. Cechinel-Zanchett, C.C.; Mariano, L.N.B.; Boeing, T.; Costa, J.C.; Silva, L.M.; Bastos, J.K.; Cechinel-Filho, V.; Souza, P. Diuretic and renal protective effect of kaempferol 3-O-Alpha-l-rhamnoside (Afzelin) in normotensive and hypertensive rats. J. Nat. Prod. 2020, 83, 1980–1989. [Google Scholar] [CrossRef]
  173. Castro, A.H.F.; Tavares, H.D.S.; Pereira, S.R.F.; Granjeiro, P.A.; da Silva, J.A.; Galdino, A.S. Production and characterization of lectin from Bauhinia holophylla (Fabaceae: Cercideae) calli. Plant Cell Tissue Organ Cult. 2018, 134, 423–432. [Google Scholar] [CrossRef]
  174. Pepato, M.T.; Baviera, A.M.; Vendramini, R.C.; Brunetti, I.L. Evaluation of toxicity after one-months treatment with Bauhinia forficata decoction in streptozotocin-induced diabetic rats. BMC Complement. Altern. Med. 2004, 4, 7. [Google Scholar] [CrossRef]
  175. Cavalcanti, E.M.; Bonafé, C.; Silva, M.G.; Gerenutti, M. Properties of Bauhinia forficata Link in rats: Behavioral evaluations. Pharmacologyonline 2011, 2, 205–211. [Google Scholar]
Plants 12 00031 g001 550
Figure 1. Literature screening procedure (flow chart).
Figure 1. Literature screening procedure (flow chart).
Plants 12 00031 g001
Plants 12 00031 g002 550
Figure 2. Biological activity of austral South American Bauhinia. Graphical representation of the number of published studies that reported each biological activity. The activities are grouped into eight categories discussed in Section 3.1, Section 3.2, Section 3.3, Section 3.4, Section 3.5, Section 3.6, Section 3.7 and Section 3.8 in the text. bau—bauhinioides; che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata.
Figure 2. Biological activity of austral South American Bauhinia. Graphical representation of the number of published studies that reported each biological activity. The activities are grouped into eight categories discussed in Section 3.1, Section 3.2, Section 3.3, Section 3.4, Section 3.5, Section 3.6, Section 3.7 and Section 3.8 in the text. bau—bauhinioides; che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata.
Plants 12 00031 g002
Table
Table 1. Main traditional uses of austral South American Bauhinia.
Table 1. Main traditional uses of austral South American Bauhinia.
SpeciesTraditional UsesReferences
affinisDiabetes.[7,24]
argentinensis *Analgesic (kidney). Hepatic disorders. Kidney disorders.[8,25]
bauhinioidesDiuretic. Kidney disorders. Refrigerant.[8,26]
cheilanthaAnalgesic (back, pain in general, headache). Anemia. Anti-inflammatory. Antilipidemic. Asthma. Blood thinner.Cancer. Depurative. Diabetes. Digestive disorders. Dysphonia and throat inflammation. Flu and cough, expectorant. Hemostatic. Helminthiasis. Hypertension. Hypocholesterolemic agent. Inappetence. Kidney disorders. Rheumatism. Sedative. Sexual impotence. Tonic. Triglyceride reducer. Urinary infection, burning in the urethra, uterus.[3,27,28,29,30]
forficata ** Antiseptic. Cardiovascular disorders. Diabetes. Hypoglycemic agent. Diuretic. Endocrine disorders. Gastrointestinal disorders. Gynecologic and obstetrics disorders. Hepatic disorders. Hypocholesterolemic agent. Indigestion flatulence. Kidney disorders. Urinary disorders. Weakness.[9,13,14,24,26,29,31,32,33,34,35]
pAbluent. Analgesic (headache). Antidandruff. Antihemorrhoidal. Antinephritic. Antitussive expectorant. Astringent. Blood depurative. Cardiotonic. Diabetes. Hypoglycemic agent. Digestive. Diuretic. Genito-urinary and hemolymphatic system. Hypotensive agent. Rheumatism. Vulnerary.[8,10,25,36,37,38]
cCistitis. Diabetes. Hypoglycemic agent. Kidney disorders, kidney stones.[1,2,3]
holophyllaAnti-obesity. Astringent. Diabetes. Hypoglycemic agent. Diuretic.[3]
microstachyaAnalgesic. Anti-inflammatory. Blood depurative. Diabetes. Hypoglycemic agent. Liver pain, spleen ache. Respiratory disorders. Urinary and gallbladder disorders.[8,13,15,31,37,39,40]
mollisnd.[41,42]
rufaAnoretic. Antihyperlipidemic agent. Astringent. Diabetes. Hypoglycemic agent. Diuretic.[3,41,43,44]
ungulataAnalgesic (stomach). Diabetes. Hypoglycemic agent. Hypocholesterolemic agent. Hypolipidemic agent. Laxative.[3,29,41,45,46]
* var. argentinensis. ** Nomenclature according to published papers. c—B. candicans; p—B. forficata subsp. pruinosa; nd—author/s mentioned the species as a medicinal species without specifying the type of use.
Table
Table 2. Biological activity of austral South American Bauhinia. The activities are grouped into eight categories (see Figure 2 and Section 3.1, Section 3.2, Section 3.3, Section 3.4, Section 3.5, Section 3.6, Section 3.7 and Section 3.8 in the text). bau—bauhinioides; che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata.
Table 2. Biological activity of austral South American Bauhinia. The activities are grouped into eight categories (see Figure 2 and Section 3.1, Section 3.2, Section 3.3, Section 3.4, Section 3.5, Section 3.6, Section 3.7 and Section 3.8 in the text). bau—bauhinioides; che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata.
SpeciesBiological ActivityStudy TypeExtract/
Compound		Part UsedStudy Model/Target Species/Cells/Enzymes/Method InvestigatedReferences
Category Detail
bauAnti-inflammatory VIVBbCIseedRabbit-activated neutrophil-induced pulmonary edema.[49]
VIVBbCIseedRat carrageenan-induced paw edema and pleurisy. Scrotal microvasculature.[50]
VIVBBLseedRat carrageenan-induced paw edema and carrageenan or TNF-α-induced peritonitis.[51]
VIVrBbCI Mice elastase-induced pulmonary emphysema.[52]
VIVrBbKI Mice elastase-induced pulmonary inflammation.[53]
Antithrombotic VIVBbKIseedVein and arterial thrombosis models in rats and mice.[54]
AntitumorAntiproliferative activity.VITBbCI, BbKIseedHUVEC human umbilical vein endothelial cells.[55,56]
VITrBbCI, rBbKI MKN-28 Hs746T (gastric), HCT116 HT29 (colorectal), SkBr-3 MCF-7 (breast), THP-1 and K562 (leukemia) human cancer cells.[57]
Other biological activitiesKunitz-tipe proteinase inhibitors activity.VITBbCIseedElastase cathepsin L and cathepsin G.[58,59]
VITBbKIseedTrypsin chymotrypsin plasmin and pancreatic and plasma kallikrein.[59,60]
Trypanosoma cruzi cruzipain inhibitor activity.VITBbCIseedTrypanosoma cruzi cruzipain.[58,59]
cheAntitumorCytotoxic activity.VITEssential oilsleafHL-60 (leukemia), MCF-7 (breast), NCI-H292 (lung) and HEP-2 (endocervical) human cancer cells.[61]
Other biological activitiesInsecticide.VITCrude extseedAedes aegypti.[62]
Larvicide.VITEthanolic extwoodAedes aegypti.[63]
VITEssential oilsleafAedes aegypti.[61]
Anticoagulant, antihypertensive and diureticAnticoagulant and antiplatelet aggregating properties.VITBfLseedBiological models of homeostasis. Human blood samples.[64]
Anticoagulant, antifrinogenolytic activities (snake venoms).VITAqueous extleafClotting disturbances in human blood samples induced by snake venoms.[65]
Antihypertensive effects.VIVAqueous extleafNormotensive and hypertensive rats.[66]
Diuretic and natriuretic activity.VIVAqueous infusion, methanolic ext, trichloromethane, ethyl acetate-butanolic fra, kaempferitrinleafNormotensive and spontaneously
hypertensive rats.		[67]
Vasorelaxant properties.VIV
c		Hydroethanolic extleafAortic rings of alloxan-induced diabetic rats.[68]
VIVExt and fra,
kaempferitrin,
kaempferol		leafAortic rings of normotensive and hypertensive rats.[69]
Antimicrobial VITHydroethanolic extleafCandida albicans.[70]
VITHydroethanolic solutionleafOral microorganism strains and mature dental biofilms.[71,72]
VITEthanolic extleafStaphylococcus aureus SA1199-B.[73]
Antioxidant VITKaempferitrinleafPeroxidation induced by ascorbyl radical in microsomes or in asolectin and phosphatidylcholine liposomes. DPPH assays and MPO activity.[74]
VITAqueous extleafSuperoxide anion radical scavenging MPO activity and ABTS radical cation assay.[75]
VIVAqueous extleafPregnant streptozotocin-induced diabetic rats blood. DNTB assay.[76]
VITSpray and
spouted bed dried ext		leafDPPH and lipid peroxidation assay.[77]
VIT f,pHydromethanolic extleafDPPH assay NO and superoxide radicals scavenging activity.[78]
VITMethanolic ext and fraleafDPPH assay.[79]
VIT
VIV		DecoctionleafLipid peroxidation (TBARS).
Orofacial dyskinesia induced by long-term treatment with haloperidol in rats.		[80]
VIT
p		Aqueous infusionleafHuman erythrocytes exposed to high glucose concentrations and egg yolk samples. Non-protein SH levels and lipid peroxidation (TBARS assay). Iron chelating DPPH and deoxyribose degradation assays.[81]
VITAqueous extleafDPPH assay. Fe2+/citrate-mediated mitochondrial lipid peroxidation in isolated rat liver mitochondria.[82]
VITHydromethanolic extleafDPPH assay.[83]
VITHydroalcoholic ext, flavonoid-rich fraleafDPPH assay measurement of reducing power and ferrous ions chelating activity.[35]
VIV
p		Aqueous infusionleafStreptozotocin-induced diabetic mice pancreas. Lipid peroxidation assay (TBARS) DCFH oxidation assay and NADPH quinone oxidoreductase 1 expression levels.[84]
VITAqueous infusionleafDrosophila melanogaster fed on high-sucrose diet.[85]
VITEthanolic and hexane extleafDPP and ORAC assays.[86]
VIVCommercial Ethanolic extleafLiver from rats exposed to Bisphenol A. TBARS assay.[87]
VIVEthanolic extleafRat male genital system. TBARS assay.[88]
VITEthanolic ext fraleafDPPH ORAC and FRAP assays.[89]
Antitumor and chemoprotectiveAntiproliferative activity.VITBfL-II
rBfL-II		seedHT-29 (colon) and MCF-7 (breast) human cancer cells.[90]
Antiproliferative and apoptotic activities.VITHY53leafHep-G2 (liver) human cancer cells.[91]
HY52leafHeLa (cervical) human cancer cells.[92]
Antitumoral activity.VIVFlavonoid-rich fra, purified kaempferitrinleafMurine melanoma.[93]
Cytostatic activity.VITrBfL Several cancer cell lines (e.g., melanoma non-small cell lung ovarian renal and breast) included in the NCI-60 panel.[94]
VITHydroethanolic extleafMCF-7(breast), NCI-ADR/RES (ovary with phenotype resistance to multiple
drugs), 786-O (kidney), NCI-H460 (lung), OVCAR-3 (ovary), HT-29 (colon), K562 (bone marrow) human cancer cells and HaCaT (normal keratinocyte) cell line.		[70]
Cytotoxic activity.VITBfLseedMCF-7 (breast) human cancer cells.[95]
VITHydro-alcoholic extleafFO-1 (melanoma) human cells.[35]
Chemoprotective effects.VITAqueous extleafBone marrow cells of Wistar rats exposed to clophosphamide.[96]
VIT
VIV		Flavonoid-rich fra, kaempferitrinleafIntestinal cells (IEC-6 cells) exposed to irinotecan. Irinotecan-induced mucositis in mice.[93]
Other biological activitiesEdema inhibition (induced by snake venoms).VIVAqueous extleafEdema induced by Crotalus durissus terrificus venom in mice.[65]
Inhibition of cholinesterase activity.VIT f,pHydromethanolic extleafCholinesterases (acetyl- or butyrylcholinesterase).[78]
Protection against vacuous chewing movements induced by haloperidol.VIVDecoctionleafOrofacial dyskinesia induced by long-term treatment with haloperidol in rats.[80]
holAntioxidant VIVHydroalcoholic ext enriched in quercetin and myricetin.leafEthanol-induced gastric ulcer in rats.[97]
AntitumorAntiproliferative and apoptotic activity. Protective effects against DNA damage.VITHydroalcoholic ext enriched in isorhamentin and quercetin derivatives.leafHep-G2 (liver) human cancer cells.[98]
Anti-ulcerAnti-ulcer activity.
Antidiarrheal effect.		VIVHydroalcoholic ext enriched in quercetin and myricetin.leafEthanol-induced gastric ulcer in rats.[97]
Anti-ulcer activity. Aqueous extleafHCl-Ethanol-induced gastric ulcer in rats or mice. NSAIDS-Bethanecol induced gastric ulcer in mice.[99]
Other biological activitiesAnti-dengue activity.VITHydroethanolic extleafDengue virus serotype DENV-2.[100]
micAnalgesicAnalgesic.VIVMethanolic ext
Quercitrin		leafAbdominal constrictions induced by injection of acetic acid in mice and capsaicin- and formalin-induced licking.[39,101]
Antihyperalgesic.VIVMethanolic ext
Quercitrin		leafCarrageenan- capsaicin- substance P- bradykinin- and adrenaline-induced mechanical hyperalgesia in rat paw.[101]
Antispasmodic effect.VIVMethanol ext, ethyl acetate fraleafSmooth muscle preparations of guineapig ileum and rat uterus.[102]
Antioxidant VITHydroalcoholic extleafDPPH and phosphomolybdenum assays.[103]
VITAqueous and hydroethanolic extleafTRAP TEAC TBARS NO superoxide and hydroxyl radical assays.[15]
VITVarious ext and fraleaf, stemDPPH and phosphomolybdenum assays.[104]
VIT
m		Ethnolic ext and fraleafDPPH ORAC and ABTS assays.[105]
Other biological activitiesPhotoprotective.VIT/
HUM		Oil-in-water emulsions/sunscreens and water-acetone or activated carbon treated-ethanol extleafIn vitro sun protection factor determination and UVA protection factor assessment.
Colipa test in human volunteers to assess sun protection factor.		[106]
rufAntimicrobial VITAqueous and ethanolic extleafStrains of Candida spp.[107]
AntitumorApoptotic activity.VITrBbKIm, modified with RGD/RGE motifs of BrTI DU145 and PC3 (prostate) human cancer cells.[108]
Inhibition of adhesion.VITBrTI and synthetic peptide containing RGD motifseedB16F10 and Tm5 murine melanoma cells.[109]
Inhibition of capillary-like tube network formation.VITrBbKIm, modified with RGD/RGE motifs of BrTI HUVEC human umbilical vein endothelial cells.[108]
Thrombolytic activity. VITHexane extleafHuman venous blood samples. Clot lysis.[110]
Other biological activitiesKunitz-tipe proteinase inhibitors activity.VITBrTIseedPlasma kallikrein and trypsin.[109]
Larvicide.VITMetanolic ext and fra. Butane, hexane, dichloromethane, ethyl acetateleafCulex quinquefasciatus.[111]
UngAntimicrobial VITAqueousleafStaphylococcus aureus Escherichia coli and Pseudomonas aeruginosa.[112]
VITEssential oilsleafCandida albicans Bacillus cereus Salmonella typhimurium Staphylococcus aureus and Citrobacter freundii.[113]
Antioxidant VITEthanolic ext and fra (chloroform, ethyl acetate, hexane, hydroalcoholic)leafDPPH phosphomolybdenum and lipid peroxidation (TBARS) assays.[114]
VITEthyl acetate frastemPhosphomolibdenum ROS NO hydrogen peroxide and lipid peroxidation (TBARS) assays in LPS- RAW 264.7 stimulated macrophages.[115]
AntitumorAntiproliferative activity.VITBULseedHT-29 (colon) human cancer cells.[116]
Cytotoxic activity.VITEssential oilsleafHL-60 (leukemia), MCF-7 (breast), NCI-H292 (lung) and HEP-2 (cervical) human cancer cells.[117]
VITBibenzylrootHL-60 (leukemia) and Hep-2 (cervical) human cancer cells.[118]
Wound healing VIVEthyl acetate fraleafSurgical wound model in mice. Monolayers of A549 (lung adenocarcinoma) human epithelial cells.[119]
Other biological activitiesInhibition of acetylcholinesterase activity.VITHexane extflowerAcetylcholinesterase.[120]
VITEssential oilsleafAcetylcholinesterase.[113]
Inhibition of matrix metalloproteinases activity.VITEthyl acetate partitionstemMatrix metalloproteinases MMP-2 and MMP-9.[121]
Kunitz-tipe proteinase inhibitors activity.VITBuXIseedTrypsin and kallikrein.[122]
Larvicide.VITEssential oilsleafAedes aegypti.[117]
Nomenclature according to published papers: f—B. forficata subsp. forficata; p—B. forficata subsp. pruinosa; c—B. candicans; m—B. microstachya var. massambabensis. ABTS—2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid; BbCI—B. bauhinioides cruzipain inhibitor; BbKI—B. bauhinioides kallikrein inhibitor; BBL—B. bauhinioides lectin; BfL—B. forficata lectin; BfL-II—B. forficata lectine II; BrTI—B. rufa trypsin inhibitor; BUL—B. ungulata lectine; BuXI—B. ungulata factor Xa inhibitor; DCFH—2,7-dchlorofluorescein; DNTB—5,5-dithio-bis(2-nitrobenzoic acid); DPPH—2,2-diphenyl-1-picrylhydrazyl; ext—extract; fra—fraction; FRAP—ferric reducing ability of plasma; HUM—human study; MPO—myeloperoxidase; NO—nitric oxide; ORAC—oxygen radical absorbance capacity; r—recombinant; ROS—reactive oxygen species; TBARS—thiobarbituric acid reactive substances; TEAC—Trolox equivalent antioxidant capacity; TNF-α—tumor necrosis factor α; TRAP—total radical-trapping antioxidant parameter; VIT—in vitro study; VIV—in vivo study.
Table
Table 3. Main antidiabetic properties and related activities of Bauhinia forficata and B. holophylla. Model animals were Wistar rats, Swiss mice or New Zealand rabbits, except where indicated.
Table 3. Main antidiabetic properties and related activities of Bauhinia forficata and B. holophylla. Model animals were Wistar rats, Swiss mice or New Zealand rabbits, except where indicated.
SppStudy Type/Treatment/
Time		Extract/
Compound		Doses/Day
Tested		Study Model/Enzymes/
Method		GenderBasal GlycemiaEffectsReferences
for *VIV/
O/40d
c		Aqueous infusion20 g/LALX diabetic rats.MX = 181 and 36,927 mg/dL– No hypoglycemic activity.
– No improvement in glucose tolerance.
– No reduction in cholesterol levels.
– No reduction in water and food intake.
– No changes in body weight.		[123]
VIV/O/31dDecoction150 g leaf/L; 352 ± 78 mL/kgSTZ diabetic rats and normal rats.M>500 mg/dL+ Hypoglycemic activity in diabetic rats.
– No hypoglycemic activity in normal rats.
+ Reduction in urine glucose levels.
– No changes in hepatic glycogen.
– No reduction in triglycerides and cholesterol.
+ Reduction in urinary urea.
– No reduction in food and liquid intake.
– No changes in body weight.
– No reduction in urinary volume.		[124]
VIV/O/AN-butanol fra400, 600, 800 mg/kgALX diabetic rats and normal rats.MX = 3305 mg/dL+ Hypoglycemic activity in diabetic and normal rats.
– No improvement in glucose tolerance in normal rats.		[125]
VIV/O/20dAqueous ext500–1000 mg/kgSTZ diabetic pregnant ratsF>200 mg/dL+ Increment of hepatic glycogen.
– No hypoglycemic activity.
– No control of total lipid, triglyceride and cholesterol levels (lower mean values observed).
+ Reduction in uric acid concentration.
– No changes in total protein and albumin levels.		[126]
VIV O/A
IV/A
c		Methanolic ext and fra
butanolic fra		8 mg/kgALX diabetic rabbits.F-M250–320 mg/dL+ Hypoglycemic activity.
+ Improvement in glucose tolerance.
+ Reduction in urine glucose levels.
+ Reduction in urine volume.		[127]
VIV/
O/A
VIT		Purified kaempferitrin100 mg/kgALX diabetic rats and normal rats.
Soleus muscle from diabetic and normal rats.		M25–30 mmol/l+ Hypoglycemic activity in diabetic rats.
+ Stimulatory effect of glucose uptake in muscle from normal rats.
– No reduction in glucosuria in normal and diabetic rats.
– No changes in protein synthesis in muscle from normal and diabetic rats.		[128]
VIV/O/7dAqueous, ethanolic and hexanic ext200 and 400 mg/kgALX diabetic rats.M>200 mg/dL+ Hypoglycemic activity.
+ Reduction in triglycerides, total cholesterol and HDL-cholesterol.
– No reduction in LDL levels.		[129]
VIV/O/APurified kaempferitrin50, 100, 200 mg/kgALX diabetic rats and normal rats.M25–30 mmol/l+ Hypoglycemic activity in normal and diabetic rats.
– No improvement in glucose tolerance in normal rats.		[74]
VIV/O/AAqueous infusion1 g/kg/0.5 mL wat
er		Rats and mice exposed to Tityus serrulatus scorpion venom.M + Hypoglycemic activity in treated rats.
– No hypoglycemic activity in untreated rats.
+ Delay in glycogenolysis (but
not avoidance).
– Decrease of serum levels of insulin induced by venom.
– Enhanced venom lethality in mice.		[130]
VIV/O/AAqueous ext10% w/vNormoglycemic mice.M + Hypoglycemic activity.[131]
VIV/O/20dAqueous ext500–1000 mg/kg, 2 dosesSTZ diabetic pregnant rats and normal rats.F>300 mg/dL– No hypoglycemic activity in diabetic and normal rats.
– No improvement of various maternal reproductive outcomes in diabetic rats.		[76]
VIV/O/7dSpray-dried, oven-dried, wet granulated ext200 mg/kgSTZ diabetic rats.M>200 mg/kg body wt+ Hypoglycemic activity.
– No prevention of decrease in liver glycogen.		[132]
VIV/
O/14d
c		Aqueous-ethanol ext120 mg/kgALX diabetic rats.F-M200–300 mg/dL+ Hypoglycemic activity.[68]
VIV/O/35dSpouted bed-dried hydroalcoholic ext0.125 g/L and 0.25 g/L, 2 doses of 1 mLSTZ diabetic rats.MX = 514 mg/dL– No hypoglycemic activity.
– No reduction in urinary glucose.
– No reduction in cholesterol, triglycerides and HDL-cholesterol levels.
– No reduction in water and food intake.
– No changes in body weight.
– No reduction in urine volume, urinary urea and proteinuria.
– Hepatic toxicity: increament of aspartate and alanine aminotransferase activities.		[133]
VIV/O/20dAqueous ext800 mg/kgNonobese diabetic (NOD) mice.
Isolated salivary glands.		F>300 mg/dL+ Hypoglycemic activity.
+ Weight recovery.
+ Reduction in urine pH and proteinuria.
– No improvement in salivary glands tissue recovery.		[134]
VIV/
O/21d
p		Aqueous infusion1 mg/mL
(313 mg/kg)		STZ diabetic mice.M>300 mg/dL– No hypoglycemic activity.
– No changes in liver/body weight ratio.		[84]
VIVAqueous infusion5 mg/mL mediumDrosophila melanogaster fed on high-sucrose diet.- + Reduction of hemolymph glucose levels.
+ Reduction of the
hemolymph levels of triacylglycerols.
+ Improvement of the effects induced by diet intake (developmental time, survival,
body weight).		[85]
VIT
c		Butanol ext0.001–0.07 mg/mg proteinIsolated gastric glands of ALX diabetic and normal rabbits.F-M200–260 mg/dL+ Stimulatory effect of glucose uptake in normal and diabetic glands.[135]
VIT
f
VIT
p		Hydromethanolic ext α-glucosidase activity. + Inhibition of activity in B. forficata.
– No inhibition of activity in B. forficata subsp. pruinosa.		[78]
VITPurified kaempferitrin0.001, 0.0, 0.1, 1, 10, 100, 1000 ηMSoleus muscle from ALX diabetic and normal rats.M + Stimulatory effect of glucose uptake in muscle from normal rats.
+ Increase in glycogen content in muscle from diabetic rats.
+ Stimulation glycogen synthesis in muscle from normal rats.
+ Increment in protein synthesis in muscle from normal rats.		[136]
VITHydromethanolic ext α-glucosidase activity. ± Weak inhibition of activity.[83]
VITHexane ext Ethanolic ext α-glycosidase, α-amylase and lipase activity.
method.		 + Inhibition of enzyme activity.
+ Antiglycation activity.		[86]
VITEthanolic ext fra α-glycosidase, α-amylase and lipase activity.
BSA/FRU, BSA/MGO and Arg/MGO methods.		 + Inhibition of enzyme activity.
+ Antiglycation activity.		[89]
HUM/O/10mAqueous infusion
(tea)		A dessert spoon of grounded leaves in water, 3 dosesType 2 diabetes volunteers (n = 26) and diabetic control group (n = 29).F-M148.70 mg/dL
154.35 mg/dL		– No hypoglycemic activity.
– No reduction in glycated hemoglobin values.
– No changes in body mass index values.
+ No changes in serum creatinine and cortisol concentration.		[137]
HUM/
O/3m
p		Aqueous infusion, containing rutin and trigonelline0.15% w/v (containing rutin 2.80 μg/mL and trigonelline 2.87 μg/mL), 3 dosesType 2 diabetes volunteers (n = 11) and prediabetic volunteers (n = 4).F-MX = 155.57 md/dL+ Reduction in glycated hemoglobin values.
– No hypoglycemic activity.
– Increase in diuresis.
– No correlation between weight and glycemia.		[138]
HUM/O/3mAqueous infusion, containing rutin and trigonelline (tea)0.4% w/v (containing rutin 1.02 mg and trigonelline 4.30 mg, in 200 mL), 2 dosesType 2 diabetes mellitus volunteers (n = 25).ndX = 268 md/dL
(post-prandial)		+ Reduction in glycated hemoglobin values.
– No reduction in postprandial glycemia.
+ Reduction in triglycerides and total cholesterol levels (not clinically significant).
– No changes in body weight.		[139]
holVIV/O/21dAqueous ext400 mg/kgSTZ diabetic rats and normal rats.F>300 mg/dL– No hypoglycemic activity in normal and diabetic rats.
– No improvement in glucose tolerance in normal and diabetic rats.
+ Reduction in HDL-cholesterol levels in diabetic mice.
– No reduction triglycerides, cholesterol and VLDL levels.
– No reduction in water and food intake.
+ Reduction in total protein levels.
– Hepatic toxicity: reduction in body weight and increment of aspartate and alanine aminotransferase activities.		[140]
VIV/O/14d

VIT/
VIV		Ethanolic ext400 mg/kgSTZ diabetic mice and normal mice.nd>250 mg/dL+ Hypoglycemic activity in diabetic mice.
+ Improvement in glucose tolerance in diabetic mice.
+ Increment of hepatic glycogen.
– No changes in muscle glycogen.
+ Activation of gene and protein expression of enzymes involved in liver and muscle glycogenesis and glucose uptake in the muscle.
+ Inhibition of gene and protein expression of liver gluconeogenesis enzymes.
+ Inhibition of α-glucosidases (α-amilase and maltase) activity in vitro and in vivo.		[141]
* Nomenclature according to published papers: f—B. forficata subsp. forficata; p—B. forficata subsp. pruinosa; c—B. candicans. A—acute; Arg—arginine; AXL—alloxan-induced; BSA—bovine serum albumin; d—day; ext—extract; fra—fraction; FRU—frutose; HUM—clinical study in humans; IV—intravenous administration; MGO—methylglyoxal; m—month; nd—no data; O—oral administration; STZ—streptozotocin-induced; VIT—in vitro study; VIV—in vivo study.
Table
Table 4. Chemical constituents from austral South American Bauhinia. Taxa and compound nomenclature according to published papers. che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata; uru—uruguayensis.
Table 4. Chemical constituents from austral South American Bauhinia. Taxa and compound nomenclature according to published papers. che—cheilantha; for—forficata; hol—holophylla; mic—microstachya; ruf—rufa; ung—ungulata; uru—uruguayensis.
SppChemical ConstituentsReferences
cheFlavonoids: Present but not characterized
Other compounds: α-copaene, α-guaiene, α-gurjunene, α-humulene, α-muurolol, α-pinene, α-terpineol, α-ylangene, β-colacorene, β-elemene, β-gurjunene, β-pinene, δ-cadinene, δ-elemene, λ-cadinene, λ-eudesmol, λ-muurolene, 1-epi-cubenol, 2,3-dihydro-farnesol, allo-aromadendrene, aromadendrene, bicyclogermacrene, bulnesol, camphene, caryophyllene, cubenol, (E)-bisabol-11-ol, (E)-caryophyllene, elemol, germacrene D, globulol, humulene epoxide II, limonene, maaliol, myrcene, phytol, sabinene, spathulenol, terpinen-4-ol, trans-b-guaiene, trans-isolongifolanone, tricyclene, viridiflorene, viridiflorol		[61,142]
forFlavonoids: aromadendrin, catechin, epicatechin, eriodictyol, gallocatechin, hispidulin, isoquercitrin, isorhamnetin-3-O-glucoside, isorhamnetin-3-O-rhamnosyl rutinoside, isorhamnetin-3-O-rutinoside, kaempferol, kaempferol-3-(2/3/4-di-rhamnosyl) glucoside, kaempferol-3-O-(2-rhamnosyl) glucoside-7-O-rhamnoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-(2-rhamnosyl) rutinoside-7-O-rhamnoside, kaempferol 3-O-(4-O-p-coumaroyl) glucoside, kaempferol-3-O-(α)-glucoside-(1′′′6′′)-rhamnoside-7-O-(α)-rhamnoside, kaempferol-3-O-[α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl]-7-O-α-L-rhamnopyranoside, kaempferol-3-O-dirhamnoside, kaempferol-3-O-glucoside, kaempferol-3-O-rhamnoside, kaempferol-3-O-rhamnosyl rutinoside, kaempferol-3-O-robinoside, kaempferol-3-O-rutinoside, kaempferol-3-O-rutinoside-7-O-rhamnoside, kaempferol-3-rhamnoside, kaempferol-7-O-glucoside, kaempferol-7-O-(α)-rhamnoside, kaempferol-7-O-α-L-rhamnopyranoside, kaempferol-37-O-(α)-dirhamnoside (kaempferitrin), kaempferol-arabinoside- rhamnoside, liquiritigenin, luteolin-C-hexoside, myricetin, myricetin-3-O-arabinopiranoside, myricetin-3-O-galactoside, myricetin-3-O-rhamnoside, myricetin-O-(O-galloyl)-hexoside, myricetin-O-(O-galloyl)-hexoside epigallocatech-(48) epicatechin, naringenin, naringin, quercetin, quercetin-O-arabinoside, quercetin-3-arabinoside, quercetin-3-O-(2-rhamnosyl)rutinoside-7-O-rhamnoside, quercetin-3-O-α-L-pyranoside, quercetin-3-O-[α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl]-7-O-α-L-rhamnopyranoside, quercetin-3-O-hexoside (isoquercetin), quercetin-3-O-galactoside, quercetin-3-O-rhamnoside (quercitrin), quercetin-3-O-rhamnosyl rutinoside, quercetin-3-O-rutinoside-7-O-rhamnoside, quercetin-3-O-rutinoside (rutin), quercetin 3-rutinoside-7-rhamnoside, quercetin-37-di-O-α-L-rhamnopyranoside, quercetin-37-di-O-rhamnoside, quercetin-O-hexoside, quercetin-O-(O-galloyl)-hexoside, quercitrin, taxifolin-3-O-rhamnoside
Other compounds: 2,4,6-trihydroxy-octadecadienoic acid, α-bisabolol, α-bulnesene, α-cadinol, α-copaene, α-humulene, α-pinene, β-caryophyllene, β-elemene, β-ocimene, β-pinene, ß-sitosterol, γ-elemene, λ-elemene, benzyltartaric acid, bicyclogermacrene, caffeic acid, caryophyllene oxide, chlorogenic acid, copaene isomer, dihydroxyhexadecanoic acid, eicosane, epi-α-muurolol, ellagic acid, epigallocatechin-(4,8)epicatechin, eriodictyol, ferulic acid, gallic acid, germacrene, globulol, hispidulin p-coumaric acid, hydroxy-octadecatrienoic acid, isophytol, protocatechuic acid, rosmarinic acid, sabinene, salicylic acid, sinapic acid, spathulenol, syringic acid, trans-caffeic acid, trihydroxyphenanthren-2-glycoside, umbelliferone, vanillic acid, (Z)-β-farnesene, (Z,E)-farnesol, (Z,Z)-farnesol		[35,69,78,80,82,83,85,88,89,125,131,143,144,145,146,147]
subsp. pruinosa
Flavonoids: isorhamnetin-3-O-rutinoside, kaempferol, kaempferol-3-(2/3/4-di-rhamnosyl) glucoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-robinoside, kaempferol-3-O-rutinoside, kaempferol-37-dirhamnoside (kaempferitrin), myricetin-3-O-arabinopiranoside, quercetin, quercetin-3-O-rutinoside (rutin), quercetin-3-O-(2-rhamnosyl) rutinoside, quercetin-3-O-(2/3/4-di-rhamnosyl) glucoside, quercetin-37-di-O-rhamnoside
Other compounds: trigonelline		[78,81,84,138,139,148,149,150]
B. candicans
Flavonoids: kaempferol-3-O-β-D-glucopyranosyl-(6→1)-β-L-rhamnopyranosyl-7-O-α-L-rhamnopryranoside, kaempferol-37-O-α-L-dirhamnoside (kaempferitrin), quercetin-37-O-α-L-dirhamnoside, quercetin-3-O-β-D-glucopyranosyl-(6→1)-β-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside		[68,135]
holFlavonoids: 3-O-substituted flavonol, isorhamnetin, kaempferol-O-pentoside, luteolin, luteolin-deoxyhexose, myricetin-O-deoxyhexoside, myricetin-O-hexoside, myricetin-O-pentoside, quercetin, quercetin-3-O-deoxyhexoside, quercetin-3-O-hexoside, quercetin-O-deoxyhexoside, quercetin-O-hexoside, quercetin-O-pentoside, quercetin-O-xilopyranoside[97,98,100,141]
micFlavonoids: catechin, kaempferol-3-O-rhamnoside, myricitrin, quercetin-3-rhamnoside (quercitrin), vitexin (apigenin 8-C-glucoside)
Other compounds: gallic acid, hexatriacontane, methyl gallate		[15,39,151]
var.massambabensis
Flavonoids: astragalin-2″6″-O-digallate, kaempferol-3-O-rhamnoside		[105]
rufOther compounds: α-amorphene, α-cadinol, α-fenchene, α-gurjenene, α-pinene, γ-cadinene, δ-cadinene, allo-aromadendrene, aromadendrene, bicyclogermacrene, cis-a-bisabolene, germacrene, globulol, lepidozenol, spathulenol, sinularene, viridiflorol[145]
ungFlavonoids: Fisetinidol, liquiritigenin, naringenin, quercetin, quercetin arabinofuranoside, quercitrin
Other compounds: 2′-hydroxy-3,5-dimethoxy-4-methylbibenzyl, 2′-hydroxy-3,5-dimethoxybibenzyl, 3-O-methyl-D-pinitol, 6,9-guaiadiene, 8-α-11-elemenedio, α-cadinol, α-calacorene, α-copaene, α-cubebene, α-guaiene, α-humulene, β-bourbonene, β-caryophyllene, β-copaene, β-elemene, β-selinene, γ-cadinene, γ-ermacrene, γ-muurolene, allo-aromadendrene, betulinic acid, caryophyllene, caryophyllene oxide, cubenol, cyclosativene, (E)-caryophyllene, eleagnine, eriodictyol, glutinol, guibourtinidol, harmane, humulene epoxide, humulene epoxide II, junenol, pacharin, sitosterol, spathulenol, stigmasterol, taraxerol, taraxerone		[115,117,118,119,152,153]
uruFlavonoids: kaempferol-3-rhamnoside, kaempferol-galloyl-rhamnoside, quercetin-3-rhamnoside (quercitrin), quercetin-galloyl-rhamnoside[150]
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MDPI and ACS Style

Fortunato, R.H.; Nores, M.J. “Cow’s Hoof” (Bauhinia L., Leguminosae): A Review on Pharmacological Properties of Austral South American Species. Plants 2023, 12, 31. https://doi.org/10.3390/plants12010031

AMA Style

Fortunato RH, Nores MJ. “Cow’s Hoof” (Bauhinia L., Leguminosae): A Review on Pharmacological Properties of Austral South American Species. Plants. 2023; 12(1):31. https://doi.org/10.3390/plants12010031

Chicago/Turabian Style

Fortunato, Renée Hersilia, and María Jimena Nores. 2023. "“Cow’s Hoof” (Bauhinia L., Leguminosae): A Review on Pharmacological Properties of Austral South American Species" Plants 12, no. 1: 31. https://doi.org/10.3390/plants12010031

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