Traditional Knowledge, Phytochemistry, and Biological Properties of Vachellia tortilis

Vachellia tortilis is a medicinal plant of the Fabaceae family, widely distributed in arid and semi-arid regions of North, East and Southern Africa, the Middle East and the Arabian Peninsula. In traditional medicine. It’s commonly used to treat certain ailments, including diabetes, asthma, hepatitis and burns. Different scientific search databases were used to obtain data on V. tortilis, notably Google Scholar, Scopus, Wiley Online, Scifinder, Web of Science, ScienceDirect, SpringerLink, and PubMed. The knowledge of V. tortilis was organized based on ethnomedicinal use, phytochemistry, and pharmacological investigations. Phytochemical studies revealed the presence of a variety of phytocompounds, including fatty acids, monosaccharides, flavonoids, chalcones, and alcohols. Essential oils and organic extracts prepared from V. tortilis showed several biological properties, specifically antibacterial, antifungal, antiparasitic, antioxidant, antiproliferative, anti-diabetic, and anti-inflammatory effects. Antimicrobial and antiparasitic activities are due to the disturbance of cellular membranes and ultra-structural changes triggered by V. tortilis phytochemicals. While physiological and molecular processes such as apoptosis induction, preventing cell proliferation, and inflammatory mediators are responsible for the anti-diabetic, anti-cancer, and anti-inflammatory activities. However, further investigations concerning pharmacodynamics and pharmacokinetics should be carried out to validate their clinical applications.


Introduction
Fabaceae family contains several medicinal plants that have been recognized for their therapeutic potential in the treatment of a variety of ailments. Among these medicinal species, V. tortilis is a medicinal plant that is extensively employed in traditional pharmacopeia for its therapeutic properties [1]. This species distribution includes arid and

Botanical Description and Ecological Factors
In extremely dry conditions, a medium tree that is 4-15 m tall and has multiple trunks and an umbrella shape is reduced to a little wiry shrub (1 m tall maximum).
V. tortilis ( Figure 2) bears little brownish hooked thorns and straight white thorns [10]. The immature stems and branches are reddish brown with grey lenticel stems, which transform to dark brown when mature, and the bark is a strong, fissured grey-brownblack color [11].
The pairs of spines are organized, with some spines being short and hooked (up to 5 mm long) and others being long and straight (up to 10 cm long). Having 4-10 pinnae and a maximum length of 2.5 cm, leaves can actually be large (15 leaflets pairs each). White,

Botanical Description and Ecological Factors
In extremely dry conditions, a medium tree that is 4-15 m tall and has multiple trunks and an umbrella shape is reduced to a little wiry shrub (1 m tall maximum).
V. tortilis ( Figure 2) bears little brownish hooked thorns and straight white thorns [10]. The immature stems and branches are reddish brown with grey lenticel stems, which transform to dark brown when mature, and the bark is a strong, fissured grey-brownblack color [11].
The pairs of spines are organized, with some spines being short and hooked (up to 5 mm long) and others being long and straight (up to 10 cm long). Having 4-10 pinnae and a maximum length of 2.5 cm, leaves can actually be large (15 leaflets pairs each). White, fragrant flowers are paired with flat, twisted, coil-like pods that resemble springtime. They blossom from May to June, bear fruit in July, and reach maturity from November to February. With longitudinal veins slightly constricted between the seeds, post-floral yellow-brown pods measuring 5-15 cm long and containing 5-18 seeds are present [9][10][11].
The V. tortilis tree can be found in a wide variety of environments, from subtropical deserts to tropical deserts to very dry forests. With an estimated minimum annual The immature stems and branches are reddish brown with grey lenticel stems, which transform to dark brown when mature, and the bark is a strong, fissured grey-brown-black color [11].
The pairs of spines are organized, with some spines being short and hooked (up to 5 mm long) and others being long and straight (up to 10 cm long). Having 4-10 pinnae and a maximum length of 2.5 cm, leaves can actually be large (15 leaflets pairs each). White, fragrant flowers are paired with flat, twisted, coil-like pods that resemble springtime. They blossom from May to June, bear fruit in July, and reach maturity from November to February. With longitudinal veins slightly constricted between the seeds, post-floral yellow-brown pods measuring 5-15 cm long and containing 5-18 seeds are present [9][10][11].
The V. tortilis tree can be found in a wide variety of environments, from subtropical deserts to tropical deserts to very dry forests. With an estimated minimum annual precipitation requirement of 10 mm and a maximum of over 100 mm, an expected annual temperature of 18-28 • C, and a pH of 6.5-8.5, it can withstand a wide range of precipitation. This species can withstand temperatures of up to 50 • C in hot, arid conditions. The um-Plants 2022, 11, 3348 4 of 21 brella tree thrives in the lowlands. It develops in regions where the annual rainfall exceeds 1000 mm. It is also drought tolerant, surviving in climates with an annual rainfall of less than 100 mm and a long and erratic dry season. The tree thrives in soils with a neutral pH. It develops lengthy roots in soils that are at least 0.25 m deep. The plant remains shade tolerant in shallow soil and must be spaced widely to allow for the growth and proliferation of its lateral roots [10].

Ethnomedicinal Use
V. tortilis is one of the most useful medicinal plants in Morocco, particularly in the southern area. Plant parts are employed in folk medicine for a variety of medicinal benefits. Different traditional uses of A. tortilis in different countries to treat different pathologies are shown in Table 1.
The pharmacological effects of the leaves of V. tortilis include antibacterial, antidiabetic, antiparasitic, cytotoxic, and anti-inflammatory characteristics [12][13][14]. In traditional medicine, root extracts are applied as cytotoxic and antiparasitic medicines [14]. Similarly, fruits exhibit cytotoxic and antimicrobial properties [15]. However, the gum serves as an antibacterial agent [3]. V. tortilis materials are prepared according to various methods to treat a variety of disorders (Table 1). Infusion, decoction and powdered materials are used in traditional medicinal preparations.
In Moroccan pharmacopeia, stomach disorders and diabetes were the most common medical applications of V. tortilis [1,12]. In fact, roots, fruits, and leaves were used as both decoctions and powders by the population of the Al Haouz Rhamna region to treat diabetes [12]. However, plant pod powder is used by the Moroccan Sahara population in Tan Tan [16].
Digestive problems are relieved with powdered leaves [17]. The bark of V. tortilis has been used in traditional medicine as an astringent, demulcent, detergent, hemostatic, and expectorant for angina, neuralgia, asthma, hepatitis, and jaundice [1]. Furthermore, the Tata province's inhabitants (Morocco) used fruit to manage kidney stones using a decoction [1]. They are also used, by mixing the powder with olive oil as a poultice, for burns treatment [17].
In the Southern Algerian Sahara (Tassili N'ajjer), Hammiche and Maizahave reported that powdered fruit and seeds exert an effect against stomach diseases, diarrhea, and aches [19]. However, in Yemen, only V. tortilis fruits are used for digestive problems and similar purposes [15]. In addition, roots reduce bloating in the population of Samburu in Northern Kenya [18]. In Central Sudan (Soba area), V. tortilis is known to be used for malaria, swollen joints and skin disorders [20]. The local population of the Eastern Desert of Egypt (Wadi El-Gemal National Park) uses V. tortilis gum against jaundice, stomach acidity and ocular affections [21].
In Northern Burkina Faso, V. tortilis is used in traditional medicine for tropical infectious diseases such as schistosomiasis and malaria, as well as other illnesses (pulmonary and urogenital) [23]. Additionally, people in many parts of Africa use the trunk bark, which has diuretic and hypotensive qualities [13].

Phytochemical Compounds
The main compounds included in V. tortilis vegetable oil, essential oils, and extracts are listed in Table 2. The materials used, the type of extract, the chemical compounds found, and the corresponding chemical classes are all stated in this table for each nation. According to the literature, chromatographic and spectroscopic techniques were used to identify the phytochemicals of V. tortilis. Chemical compositions reported in the literature are different due to the plant parts utilized and the countries from which they were procured ( Table 2). The phytochemicals of V. tortilis are listed below according to the corresponding chemical classes.
Fatty acids are mainly extracted from seed oil with petroleum ether (40-60 • C) using a soxhlet. Linolenic acid was found to be the most abundant, then palmitic acid, oleic acid, and stearic acid [28]. However, in Egypt (South and North Sinai) fatty acid profile was different, and linoleic acid was the main component [8].

Monosaccharides
The monosaccharide compounds were identified in the gum exudates of A. tortilis. The carbohydrate composition has only been documented through one research from India. It includes mostly L-arabinose, D-galactose, L-rhamnose, D-mannose, and D-glucose [26].

Alcohols
A study conducted on Acacia ( Figure 5) collected in Somalia showed that an aqueous extract of stem bark covered with gum (decoction) contains alcohols.

Alcohols
A study conducted on Acacia ( Figure 5) collected in Somalia showed that an aqueous extract of stem bark covered with gum (decoction) contains alcohols. [27].

Antibacterial Activity
Previous investigations reveal the antibacterial effects of this medicinal plant against Gram-positive and Gram-negative bacteria species. Table 3   Plants have grown in popularity as functional food ingredients. Phytochemical profiles vary depending on the season, growth conditions, location, and environmental changes. The chemical composition of V. tortilis extracts differs qualitatively and quantitatively depending on the plant part used, the plants' growing area, and the period of the vegetative phase.

Antibacterial Activity
Previous investigations reveal the antibacterial effects of this medicinal plant against Gram-positive and Gram-negative bacteria species. Table 3 summarizes antibacterial investigations conducted on extracts of various V. tortilis parts. Inhibition zone diameters (Ø) and minimum inhibitory and bactericidal concentrations (MIC and MBC) data are mentioned.    Ethanolic, chloroform, and acetonic extracts obtained from the aerial segment of V. tortilis antimicrobial properties of were studied against Staphylococcus aureus (ATCC25923) and Pseudomonas aeruginosa (ATCC 27853) in vitro by Abdllha and collaborators [5]. The strains were sensitive to ethanolic and acetonic extracts with diameter zones of inhibition ranging from 18 to 23 mm. Whereas no activity was found with the chloroform extract. The antibacterial property of extracts from the aerial section of V. tortilis was also investigated by the Alajmi team. The results revealed that ethanolic extract inhibited the proliferation of Escherichia coli (Ø = 19 ± 0.8 mm; MIC = 0.8 mg/mL), Staphylococcus aureus (Ø = 17 ± 0.9 mm; MIC = 0.4 mg/mL), and Pseudomonas aeruginosa germs (Ø = 16 ± 1.5 mm; MIC = 0.8 mg/mL) [30]. These differences in inhibition activities are certainly due to the difference in the plant parts used, the extraction technique, and edaphic factors. In another study, chloroform, alcoholic, petroleum ether, methanolic, and petroleum Benzin extracts of V. tortilis extracts, prepared from dry bark and fresh leaves were tested against Klebsiella oxytoca, Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The diameter of the inhibition zone in this research ranged between 7-16 mm, with Klebsiella pneumoniae being the most sensitive bacteria, including all extracts [6]. Another study showed the antibacterial action of an aqueous extract generated from plant gum by using the disk diffusion method. Salmonella typhi, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis have antibacterial activity with inhibition zone diameters of 19 ± 0.5, 17 ± 0.4, 24 ± 0.6, and 23 ± 0.1 mm, respectively [3].
Aqueous and ethanolic extracts produced from fresh leaves were tested for antibacterial activity using MIC and MBC against Escherichia coli, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis, Klebsiella pneumoniae, and Listeria monocytogenes. The MIC and MBC values varied from 1.25 to 5 mg/mL and 20 mg/mL, according to the results of [4].
Chloroform, petroleum ether, and methanol extracts inhibited more strains such as Klebsiella pneumoniae, Klebsiella oxytoca, and Pseudomonas aeruginosa compared to other types of extracts such as an ethanolic extract and an aqueous extract [6]. The results of the experiments with dried bark, which have higher inhibitory diameters than the experiments with leaves, were reversed [6]. Leaves inhibit more Klebsiella pneumonia than dry bark, later inhibits Proteus mirabilis more than Staphylococcus aureus [6]. The gum component inhibits Gram-positive bacteria, such as Staphylococcus aureus and Bacillus subtilis, as well as Gramnegative bacteria, including Salmonella typhi and Escherichia coli [3]. Gram-negative bacteria resistance to V. tortilis extracts is due to the enveloping outer membrane encircling the cell wall, which prevents hydrophobic chemicals from diffusing through the lipopolysaccharide. The main and synergistic effects of the major and minor chemical components, notably flavonoids (chalcone glycosides, flavones, flavanol, flavonol glycoside, isoflavone, flavone, and flavanols), monosaccharides, alcohols, and fatty acids, are frequently attributed to extracts antibacterial action(linolenic, linoleic, palmitic, oleic, stearic acids) [4,8,[24][25][26][27][28]31].
Although plant extracts have been proven effective against these strains, the mode of action has yet to be discovered, necessitating more investigation into their mechanism of action.

Antifungal Activity
V. tortilis antifungal activity was previously described in the literature against only three fungal strains [5,6,29]. Table 4 lists the data of previous studies on antifungal investigations from various parts of V. tortilis extracts. Using the agar-plate well diffusion method, Abdllha and his associates tested the antifungal activity of aerial part extracts against Candida albicans (ATCC90028). The acetonic extract (25 mm) and the ethanolic extract (23 mm) had the most activity against yeast, whereas the chloroform extract showed no inhibition [5].
Agar well diffusion method was also used [30] to determine the antifungal effect property of the aerial parts ethanolic extract against Candida albicans. Minimal inhibition concentration was also determined (0.8 mg/mL), which is of the same value as Acacia salicina (0.8 mg/mL), lower than Acacia laeta (1.6 mg/mL) and Acacia hamulosa (3.2 mg/mL).
Using the agar diffusion method, Al-Fatimi and colleagues found that the methanolic extract of fruit from V. tortilis had antifungal activity against Candida maltosa. The extract effectively suppressed proliferation, with an inhibition zone equal to 8 mm [15].
Ref. [6] and co-workers carried out the agar well diffusion method to evaluate the antifungal properties of methanolic extract, chloroform extract, petroleum benzin extract, and petroleum ether extract from V. tortilis aerial parts and dry bark against Candida albicans [6]. According to the experimental fungal growth, five extracts from the aerial parts exhibited inhibitory effects differently. As a result, the highest activity against Candida albicans was found using the methanolic and alcoholic extracts (Ø = 16.6 ± 0.67 and 16.6 ± 0.33 mm, respectively), subsequently the chloroform extract (Ø = 16.0 mm). The zones of inhibition for petroleum benzin and petroleum ether extracts, respectively, were 15.6 ± 0.33 mm and 15.3 ± 0.33 mm. Furthermore, similar Candida albicans inhibition activities were obtained using methanolic, petroleum benzin, and chloroform extracts from the dry bark of V. tortilis (Ø = 12.3 mm). Petroleum ether and alcohol exhibited a slight difference in this antifungal activity (Ø = 11.0 ± 1.52 and 10.3 ± 1.76 mm, respectively [6]. As previously stated, the differences in the results are related to genetic variability, environmental influences, and chemical composition. Thus, the antifungal activity is mainly due to the bioactive phytochemicals of V. tortilis (fatty acids, monosaccharides, flavonoids, and alcohols). Polyphenols are a significant class of natural compounds that includes flavonoids [32].

Antiparasitic Effects
Malaria is a serious tropical disease caused by protozoa of the Plasmodium genus. The anti-plasmodial activity of V. tortilis chloroform extract against chloroquine (CQ)resistant plasmodium was investigated in vitro (D6 clone).In comparison to chloroquine (IC 50 = 0.004 g/mL), the results showed an IC 50 equal to or higher than 10.0 µg/mL [14]. Another analysis revealed that methanolic extract exhibited anti-plasmodial potential in vitro, with an IC 50 value of 85.73 ± 3.36 µg/mL [33]. The anti-leishmanial activity of aqueous and methanol extracts from the leaves of V. tortilis appears promising against Leishmania major (IDU/KE/83 NLB-144 strain) [33].

Antioxidant Activity
Using all plant parts and processes, such as the DPPH, ABTS, FRAP, and carotenelinoleic acid approaches, several researchers have evaluated the antioxidant activity of various V. tortilis preparations (Table 5). The antioxidant properties of V. tortilis ethanolic extract were measured by Alam and coworkers using the DPPH test [7]. The results were expressed as IC 50 values, which were equal to 250.13 and 747.50 µg/mL, respectively.
According to the literature, at 500 µg/mL, the DPPH scavenging activity was in the following order: A. salicina > A. laeta > A. tortilis > A. hamulosa [7]. Surprisingly, the antioxidant activity of Acacia salicina was similar to that of the antioxidant standard rutin at amounts higher than 250 µg/mL. Acacia extracts' activities were dose-dependent, according to the results of the DPPH radical scavenging assay.
In another work, a methanolic extract of V. tortilis leaves obtained by infusion and maceration exhibited considerable DPPH radical scavenging activity [23,35]. Results obtained were expressed as 84.3 ± 9.7 mg/g dry weight equivalent of chlorogenic acid.
The acetonic and ethanolic extracts of the aerial parts had the highest radical scavenging activity, with values of 82.04 and 83.02%, respectively [5]. However, the chloroform extract exhibits the lowest scavenging activity, with an RSA equal to 42.7%.
Using testing methods, including the ABTS test, Habib and colleagues demonstrated that aqueous extract by maceration of fruit V. tortilis exhibited an antiradical effect (80.62 ± 0.14%), by the DPPH antioxidant (19.12 ± 1.34%) [36]. According to the DPPH test, a methanolic extract from Acacia fruit maceration has a radical trapping activity of 26.17% (concentration = 100 µg/mL) in a study by Al-Fatimi and colleagues [15].
The antioxidant effect of maceration-based methanolic extract of Acacia seeds was studied using the DPPH and ABTS assays in another study. Data indicates that extract has the lowest activity, with EC 50 values of 0.84 ± 0.03 and 2.22 ± 0.20 mM (TEAC), respectively [37].
Another investigation evaluated the antioxidant activity of V. tortilis gum aqueous extract obtained by maceration using the DPPH assay. As a result, 20 mg/mL gum extract exhibited a scavenging potential of 92.13 ± 0.13% [3].
The methods conducted to evaluate antioxidant activity have a specific mechanism, which explains the diversity in the results listed in Table 5. These approaches are, in effect, mutually beneficial. Thus, in order to confirm and validate the results presented in the table of extracts from A. tortilis, in vivo antioxidant activity tests should be performed.

Antiproliferative Activity
Different analytical methods highlighted the cytotoxic activity of V. tortilis, as shown in Table 6. V. tortilis leaves revealed potential in vitro cytotoxic effect, according to Ziani and colleagues. The sulforhodamine B colorimetric assay was used to determine the capacity of extracts to inhibit cell proliferation in four human tumor cell lines: NCI-H460 (non-small cell lung cancer), HeLa (cervical carcinoma), HepG2 (hepatocellular carcinoma), and MCF-7 (breast carcinoma). Elipticine was used as a positive control, and the results were expressed as Growth Inhibition values (GI 50 , µg/mL). The growth of non-tumor liver cells (PLP2) was indeed tested using different amounts of V. tortilis extracts under the same conditions as tumor cell lines. Ethanolic extract expressed a low GI 50 on the four tumor cell lines (from 33.3 to 53.0 µg/mL) [4]. Compared to the cytotoxicity data obtained by the ethanolic extract of aerial parts [30], ethanolic leaf extracts seem to have a high cytotoxic effect on HepG2 cells (IC 50 42.3 and 33 µg/mL, respectively). Acacia species have been demonstrated to have a cytotoxic effect on a variety of tumor cell lines (HepG2, MCF-7, HEK-293) ( [38]. A high GI 50 (259 ± 0.05 µg/mL) was recorded on the PLP2 cell line using the ethanolic leaves extract [4]. The lower cytotoxicity of V. tortilis extracts in the normal PLP2 cell line might be due to the specific molecular mechanisms involved in tumor cells that are not present or active in normal cell lines.
Furthermore, tumor cells that were exposed to V. tortilis extracts had a higher response than non-tumor cells, implying that they were more reactive to the phenolic chemicals present in the extracts. These substances tend to be interfering with the cell cycle, apoptosis, and cell death pathways, all of which are implicated in tumor proliferation [39,40]. According to [41], the cytotoxic effect could be attributed to epigallocatechin derivatives, which are prevalent in V. tortilis extracts, as well as a possible synergistic interaction with different Acacia active components that approach epigallocatechin derivatives. As previously reported by [42], V. tortilis contains a significant amount of esterified gallic acid and epicatechin galloyled with a significant level of hydroxyl ring substitutions, which have also been shown to inhibit the proliferation of many tumor cell lines directly. This provides a coherent explanation for cytotoxicity on human tumor cells [4].

Antidiabetic Effect
Investigations conducted on V. tortilis' anti-diabetic properties are limited. Table 7 reports the in vivo research data realized with different Acacia extracts.  [45] Because diabetes is always related to body weight loss due to muscle wasting and tissue protein catabolism, the effect of the administration of AEATP on body weight was followed [46,47]. Indeed, AEATP markedly increased body weight on the 14th day of administration and balanced the effect of STZ approximately close to the glimepiridetreated group.
Kumar and Singh assessed the anti-diabetic activity of aqueous extract of V. tortilis polysaccharide from gum exudates on streptozotocin-nicotinamide-induced diabetic rats. Dosages of 250, 500, and 1000 mg/kg were administered to male albino Wistar rats for 28 days, with all necessary controls. AEATP reduces current weight, fasting blood glucose, total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels while improving HDL levels [48].
Treatments were completed on the 21st and 28th days, and body weight was almost the same, and statistically, no significant difference was found between the glimepiride and polysaccharide tests [48]. This could be ascribed to the protective effect of polysaccharides in the control of muscle wasting, contrary to neoglucogenesis, as well as increased insulin secretion and enhanced glycemic control.
After administering polysaccharide, glycated hemoglobin was also substantially reduced (250-1000 mg/kg) as compared to the STZ-induced diabetic group with close value to those of glimepiride after 28 days of treatment [48]. Flavonoids abundant in V. tortilis are known for their ability to attenuate hyperglycemia and reduce the nonenzymatic glycation of proteins in animals [25,49,50]. Nutritional flavonoids or extracts rich in flavonoids may prevent and treat T2DM, as well as reduce diabetes complications, according to significant variables from cell and animal models. Flavonoids in the diet lower blood glucose levels by protecting pancreatic cells, stimulating insulin signaling, inducing the pancreas to release insulin, inhibiting glycogenolysis, and inhibiting neoglucogenesis, digestive enzymes, and carbohydrate metabolizing enzymes, as well as inhibiting neoglucogenesis, digestion enzymes, and carbohydrate metabolizing enzymes [51].
Certain flavonoids aglycones and their O-glycosides/C-glycosides exhibited antidiabetic effects in animal models, namely apigenin, baicalein, quercetin, kaempferol, myricetin, daidzein, luteolin, and naringenin. Leading to a shortage of data and varied animal models, determining the structure-activity interaction of flavonoids and antidiabetic effects remains difficult [51].
Lipids are well-known for their role in the pathophysiology of diabetic complications and the resulting hyperlipidemia. Diabetics have a higher risk of developing atherosclerosis than non-diabetics [52]. Interestingly, polysaccharides have shown a considerable reduction in TG and LDL-C, implying additional hypolipidemic activity that could protect against the development of cardiovascular disease and diabetes. Cholesterol levels in serum significantly decreased from 206.1 ± 3.7 mg/dL (STZ-induced diabetic group), and both 500 and 1000 mg/kg of polysaccharide normalized the elevated cholesterol to levels similar to that of glimepiride (134.2 ± 3.52 mg/dL) [48]. In the same study, Bhateja and Singh also showed that levels of total triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were significantly reduced after administration ( Figure 6). The same effectiveness was reported for VLDL levels. Otherwise, HDL levels were significantly reduced in the diabetic control group, which was close to that of glimepiride (24.44 ± 1.3 mg/kg) [48]. glucose levels by protecting pancreatic cells, stimulating insulin signaling, inducing the pancreas to release insulin, inhibiting glycogenolysis, and inhibiting neoglucogenesis, digestive enzymes, and carbohydrate metabolizing enzymes, as well as inhibiting neoglucogenesis, digestion enzymes, and carbohydrate metabolizing enzymes [51].
Certain flavonoids aglycones and their O-glycosides/C-glycosides exhibited anti-diabetic effects in animal models, namely apigenin, baicalein, quercetin, kaempferol, myricetin, daidzein, luteolin, and naringenin. Leading to a shortage of data and varied animal models, determining the structure-activity interaction of flavonoids and antidiabetic effects remains difficult [51].
Lipids are well-known for their role in the pathophysiology of diabetic complications and the resulting hyperlipidemia. Diabetics have a higher risk of developing atherosclerosis than non-diabetics [52]. Interestingly, polysaccharides have shown a considerable reduction in TG and LDL-C, implying additional hypolipidemic activity that could protect against the development of cardiovascular disease and diabetes. Cholesterol levels in serum significantly decreased from 206.1 ± 3.7 mg/dL (STZ-induced diabetic group), and both 500 and 1000 mg/kg of polysaccharide normalized the elevated cholesterol to levels similar to that of glimepiride (134.2 ± 3.52 mg/dL) [48]. In the same study, Bhateja and Singh also showed that levels of total triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were significantly reduced after administration ( Figure 6). The same effectiveness was reported for VLDL levels. Otherwise, HDL levels were significantly reduced in the diabetic control group, which was close to that of glimepiride (24.44 ± 1.3 mg/kg) [48]. Regarding the effect of polysaccharides on liver enzymes, high levels of SGOT (284.5 ± 10.21) and SGPT (161.9 ± 5.21 unit/L) in the serum of diabetic rats were lowered after administration of AEATP [48]. Normalized serum SGPT and SGOT levels are responsible for normal liver function in reversing diabetes-related organ damage.
Decreased fasting insulin levels (0.373 ± 0.026 ng/mL) and the insulin content of the pancreas (56.0 ± 2.81 ng/mg pancreas) in STZ-induced diabetic rats were also improved by AEATP [48]. Polysaccharides may improve insulin secretion by membrane depolari- Regarding the effect of polysaccharides on liver enzymes, high levels of SGOT (284.5 ± 10.21) and SGPT (161.9 ± 5.21 unit/L) in the serum of diabetic rats were lowered after administration of AEATP [48]. Normalized serum SGPT and SGOT levels are responsible for normal liver function in reversing diabetes-related organ damage.
Decreased fasting insulin levels (0.373 ± 0.026 ng/mL) and the insulin content of the pancreas (56.0 ± 2.81 ng/mg pancreas) in STZ-induced diabetic rats were also improved by AEATP [48]. Polysaccharides may improve insulin secretion by membrane depolarization, inhibiting K + -ATP channels and stimulating Ca 2+ influx. Since altered content of gut incretin is associated with type 2 diabetes in animal models, polysaccharides may stimulate incretin secretion and thus probably induce glucagon-like peptide-1 (GLP-1) increase or dipeptidyl peptidase-4 (DPP-4) inhibition [53]. Moreover, it shows that the polysaccharide effect, similar to STZ treatment, may include a reduction in oxidative stress and, consequently, oxidative damage and dyslipidemia prevention.

Anti-Inflammatory Effect
A murine macrophage-like cell line was used to study the anti-inflammatory properties of ethanolic and aqueous extracts of V. tortilis leaves collected in the Algerian Sahara [4]. RAW 264.7 cell model was stimulated by lipopolysaccharide (LPS). The anti-inflammatory activities could be explained by the presence of phenolic compounds, particularly (epi)gallocatechin derivatives. Phenolic compounds have been shown to inhibit inflammatory responses in activated Raw 264.7 cells through NO production reduction as well as inhibition of proinflammatory mediators and cytokines, including TNF-α, IL-1, IL-6, and IL-12. The use of (epi)-catechin to reduce NO production in the studied cell model has been previously reported in the literature [54,55]. In addition, a gallate ester substitution is involved in the anti-inflammatory properties of (epi)-catechins and gallic acid enhancement [56]. Epigallocatechin-3-gallate is an efficient scavenger ROS and RNS such as NO and peroxynitrite involved in the nucleus translocation of NF-kB nuclear factor from the cytoplasm [57]. Moreover, it has been previously reported that the suppression of iNOS and COX-2 enzymes and TNF-α expression is due to the reduction of NO production by acetone extract of Acacia stem bark [58].
In the study conducted by [24], ethanolic extract of V. tortilis leaves exhibited significant inhibition of COX-1 and COX-2. These enzymes are often targeted in the inflammatory response [59]. The observed effect is certainly ascribed to the richness of V. tortilis extract with rutin and catechin.

Conclusions and Perspectives
This review covered the taxonomy, medical applications, phytochemistry, and pharmacological characteristics of V. tortilis. According to published data, the biological activities of V. tortilis, as supported by conventional medical uses, are implicated by bioactive substances of plant sections cited (fruit, seeds, gum, leaves, and roots). These phytochemicals, which are involved in biological processes, include fatty acids, flavonoids, and chalcones. The fact that other compounds have not yet been recognized and classified as terpenoids makes a significant recommendation for additional phytochemical research.
Additionally, V. tortilis extracts show exceptional pharmacological qualities, such as anti-inflammatory, anti-microbial, antioxidant, and anti-diabetic action. These characteristics include cellular and molecular activities on many pathology-causing sites. Researched works revealed that the primary bioactive components of V. tortilis are the mediators of these pathways.
To confirm their effectiveness, additional research into the pharmacodynamic activities of these key bioactive chemicals needs to be done. Additionally, studies on the pharmacokinetics of the primary bioactive chemicals in V. tortilis should be conducted to demonstrate their safety.
This study provides a conventional analysis using pharmacological justifications on the functional advantages of the various V. tortilis plant parts that could be used, on the one hand, in in vivo studies for the creation and innovation of therapeutic strategies to prevent and manage type 2 diabetes, and, on the other hand, in the pharmaceutical industry, use of nanoparticles and the formulation based on non-toxic natural resources.