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Review

Ethnobotanical, Phytochemical, Toxicological, and Pharmacological Properties of Ziziphus lotus (L.) Lam.: A Comprehensive Review

by
Noureddine Bencheikh
1,*,
Fatima Zahrae Radi
2,
Jamila Fakchich
1,
Amine Elbouzidi
3,
Sabir Ouahhoud
1,
Mohammed Ouasti
1,
Mohamed Bouhrim
4,*,
Imane Ouasti
1,
Christophe Hano
5 and
Mostafa Elachouri
1,*
1
Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Boulevard Mohamed VI, B.P. 717, Oujda 60000, Morocco
2
Research Team of Chemistry of Bioactive Molecules and the Environment, Laboratory of Innovative Materials and Biotechnology of Natural Resources, Faculty of Sciences, Moulay Ismail University of Meknes, B.P. 11201, Zitoune, Meknes 50070, Morocco
3
Laboratoire d’Amélioration des Productions Agricoles, Biotechnologie et Environnement (LAPABE), Faculté des Sciences, Université Mohammed Premier, Oujda 60000, Morocco
4
Laboratory of Biological Engineering, Team of Functional and Pathological Biology, Faculty of Sciences and Technology Beni Mellal, University Sultan Moulay Slimane, Beni-Mellal 23000, Morocco
5
Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRAE USC1328, Campus Eure et Loir, Orleans University, 28000 Chartres, France
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2023, 16(4), 575; https://doi.org/10.3390/ph16040575
Submission received: 28 February 2023 / Revised: 5 April 2023 / Accepted: 8 April 2023 / Published: 11 April 2023
(This article belongs to the Special Issue Feature Reviews in Natural Products)
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Abstract

:
Ziziphus lotus (L.) Lam. (Rhamnaceae) is a plant species found across the Mediterranean area. This comprehensive overview aims to summarize the botanical description and ethnobotanical uses of Z. lotus and its phytochemical compounds derived with recent updates on its pharmacological and toxicological properties. The data were collected from electronic databases including the Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholars. It can be seen from the literature that Z. lotus is traditionally used to treat and prevent several diseases including diabetes, digestive problems, urinary tract problems, infectious diseases, cardiovascular disorders, neurological diseases, and dermal problems. The extracts of Z. lotus demonstrated several pharmacological properties in vitro and in vivo such as antidiabetic, anticancer, anti-oxidant, antimicrobials, anti-inflammatory, immunomodulatory, analgesic, anti-proliferative, anti-spasmodic, hepatoprotective, and nephroprotective effects. The phytochemical characterization of Z. lotus extracts revealed the presence of over 181 bioactive compounds including terpenoids, polyphenols, flavonoids, alkaloids, and fatty acids. Toxicity studies on Z. lotus showed that extracts from this plant are safe and free from toxicity. Thus, further research is needed to establish a possible relationship between traditional uses, plant chemistry, and pharmacological properties. Furthermore, Z. lotus is quite promising as a medicinal agent, so further clinical trials should be conducted to prove its efficacy.

1. Introduction

It is well-known that plants have been used in popular medicine since ancient times to treat and protect against a variety of human diseases [1,2]. According to the World Health Organization, the percentage of people using traditional medicine including plants is estimated to be 80% [3]. The security, efficacy, economic feasibility, and accessibility are the most important criteria justifying these traditional practices [4,5]. Recently, the traditional uses of medicinal herbs in drug therapies have grown in importance. The therapeutic efficacy of these herbs is mainly due to the presence of secondary metabolites that have interesting biological properties [6]. In fact, more than 60% of approved pharmaceutical drugs are obtained from natural sources, notably vegetation matter [7]. The use of medicinal herbs in drug therapies has grown in importance, either directly or as a crude resource for separating chemical compounds with particular bioactivities [6]. Among a range of medicinal plants, the genus Ziziphus, belonging to the Rhamnaceae family, is frequently utilized in traditional medicine to cure and alleviate health problems [2,8,9,10]. The genus Ziziphus includes 58 accepted plant species, according to World Flora Online (WFO). Among the species of this kind, Ziziphus lotus (L.) Lam. (Z. lotus) is widely used in different countries, particularly in North African countries, for treating various ailments. This plant, native to the Mediterranean region, is widely distributed in Africa as well as other areas in the Asian region (China, Iran, and South Korea) [11,12,13]. This plant species is traditionally used for treating and preventing many diseases such as diabetes, digestive system problems, urinary tract problems, contagious diseases, cardiovascular diseases, neuronal diseases, and dermal problems. Several published pharmacological studies have indicated that the extracts from various parts of Z. lotus have significant bioactivities such as antioxidant, antimicrobial, hepato-nephroprotective, antihyperlipidemic, anti-inflammatory, analgesic, and antiproliferative effects [14,15,16,17,18,19,20,21,22]. Furthermore, the assessment of the toxicity of natural products including derivatives of plant matter is necessary for the manufacturing process of pharmaceutical products. Toxicological investigations on Z. lotus extracts indicate that this plant does not represent any risk of toxicity [22,23]. Several phytochemical studies have indicated that Z. lotus extracts are abundant in natural substances such as polyphenols, flavonoids, terpenes, and phenolic acids [20,21,22,23,24,25,26,27]. These phytochemical compounds are well-known in the scientific literature for their pharmacological effects against various pathologies.
Abdoul-Azize (2016) conducted a literature review on the potential nutritional and health benefits of bioactive jujube (Z. Lotus) compounds [28]. This review collected and analyzed approximately 79 references on Z. lotus up to 2016. However, this bibliographic study focused on the phytochemistry and nutritional aspects of Z. lotus, and does not go into detail on the plant’s pharmacological activities. This prompted us to undertake the current comprehensive review, in which we covered different aspects related to Z. lotus including the botany, ethnobotany, phytochemistry, toxicology, geographical distribution, and pharmacology of this plant.

2. Methodology

In this comprehensive literature review, extensive bibliographic research was conducted to collect, analyze, and summarize the data on the botanical description, phytochemistry, ethnobotany, toxicology, and pharmacological activities of Z. lotus. Web of Science, Scopus, PubMed, ScienceDirect, SpringerLink, and Google Scholars were used to examine the published articles on Z. lotus. For this purpose, we used a list of keywords such as antioxidant activities, antidiabetic, antimicrobial effects, hepatoprotective effects, nephroprotective effects, analgesic effects, anticancer effects, anti-inflammatory effects, antiproliferative effects, and anti-obesity effects, combined with Z. lotus. The period in which we conducted the literature search was from 2021 to 2022. All English and French articles on Z. lotus were reviewed and included in this comprehensive review. The title of the investigation was used as the first step in identifying and reviewing the consolidated literature. If the study’s title and abstract were uncertain regarding the inclusion or exclusion from the current comprehensive study, the full text was examined. The chemical structures of the main phytochemical compounds present in the Z. lotus extracts were designed using ChemDraw 18.1 software.

3. Botanical Description

The Ziziphus lotus L. (Z. lotus) is a spiny fruit shrub, and a member of the family Rhamnaceae. It grows in tufts that are a few meters in diameter and up to two meters high, and is commonly called “Sedra” in North Africa (Figure 1A) [29]. Flowers of Z. lotus are small, axillary, bisexual, pentameric, and grouped in a cymose inflorescence, with sepals open in the star, small petals, and upper ovary, blooming in June–July (Figure 1B) [30]. The fruits of Z. lotus are drupes with welded stones, having the shape and size of a beautiful olive, first green, then young, and finally dark red at maturity from September to October (Figure 1C,D) [14]. The fructification begins in the fourth year in full yield around the age of fifteen; it is very productive when it receives copious watering during the summer [14]. The plant has oblong, whole-margined, short-petiolate, glabrous, alternating, deciduous leaves, and each leaf bears at its base two stipules transformed into an uneven and vulnerable thorn (Figure 1B) [14].

4. Eco-Geographical Features

Typically, Z. lotus is found in dry and semi-arid regions, particularly in the Mediterranean region [16]. It grows in a few southern European nations including Greece, Italy, and Spain. It is also found in western Asia and is very common in northern Africa from Morocco to the Egyptian Sahara [31]. It reappears on the island of Socotra, in Yemen, and throughout the Middle East including Cyprus, Turkey, Palestine, and Syria [32]. It is also distributed in Iran, China, and South Korea [13]. Z. lotus can adapt to a wide range of climatic circumstances. Due to its late blooming, it is more resistant to winter frosts, up to −15 °C, than spring frosts (May–July) [11]. It is a sun plant reserved for warm and dry climates. It can withstand drought well and needs a lot of heat (maximum 45 °C) to bear fruit [31]. This species is adapted to areas with low rainfall [33]. A variety of soil types are tolerated by Z. lotus. It favors deep, sandy soils that are neutral to slightly alkaline and can withstand salt [31]. This plant can be encountered in desert areas with very low rainfall and grows in rocky areas, cliffs, and foothills. It reproduces vegetatively with a low propagation by seedling, its thermal optimum is 35 °C, and its germination is rare because the seedling requires the treatment of nuclei by the digestive juices of animals [34].

5. Ethnomedicinal Uses

Table 1 summarizes the traditional knowledge on the therapeutic uses of Z. lotus. This plant is known in the North African region under the name “Sedra” and its fruits “Nbeg” [9,10,35]. Numerous ethnobotanical field works carried out in different regions of Morocco have revealed a broad range of traditional medicinal applications of Z. lotus. In fact, the leaves and seeds of this species are used in decoctions, raw or fresh, in the northeast of Morocco, to treat muscle ailments, diabetes, urinary tract problems, metabolic abnormalities, and skin and digestive problems [8]. However, in northeast Morocco, the leaves, roots, and fruits of this herb are used in powder, decocted, and in an infusion to treat kidney stones, renal colic, pyelonephritis, and polycystic kidney disease [36]. In the Moroccan region of Fez-Meknes, the fruits or leaves of Z. lotus are utilized against kidney stones [37]. In the High Central Atlas of Morocco, where the plant is known by its vernacular name “Azgour”, the fruit and the leaf in the decoction, infusion, and powder are frequently used as aperitifs, anti-ulcer remedies, anti-diabetic agents, and wound-healing agents [38]. In the Agadir Ida Outanane region, the decoction of seeds is used for problems with diabetes [39]. In Algeria, Z. lotus is commonly used for treating numerous health problems. Indeed, in the El-Bayadh region, the leaves in the decoction are used externally or internally as antitussive and antiseptic [40]. Additionally, the Z. lotus roots and leaves are extensively used in the Tlemcen region to cure diabetes, ulcers of the esophagus, colon, body aches, and arthritis [41,42]. The decoction, infusion, and powder of leaves and fruits are used in the M’Sila area of Algeria as an eczema treatment, anti-inflammatory, and pectoral support [43,44,45]. In the Algerian Sahara region (Oued Righ), the decoction and maceration of the parts of Z. lotus are used as tonics and diuretics, emollients, sedatives, and anti-inflammatories [46]. The study realized in the region of Ouargla indicated that the decoction and maceration of the fruits, leaves, and roots were used as moisturizers, sedatives, and diuretics [47]. In Mauritanian ancestral medicine, the traditional uses of Z. lotus are significantly broadened. In fact, the plant known as “Sdar hreytek” is strongly advised against stomach and epigastric pain in the district of Adrar in Mauritania [48]. In traditional Libyan medicine, the bark, fruit, leaves, and roots of Z. lotus are utilized against constipation, stomach disorders, hair parasites, gastritis, sciatica, abscesses, batteries, strengthening and activation, and hepatitis [49,50,51]. In Jordanian folk medicine, the seeds and fruits of the plant are recommended against cough, measles, deworming, and as an antispasmodic [52,53]. In Palestine, the plant is known under its local name “Zyzafun”, and its leaves are used as a disinfectant [54].

6. Phytoconstituents of Z. lotus

Numerous earlier investigations focused on the phytochemical composition of extracts from various Z. lotus parts have been published [17,19,20,21,24,25,26,27,101,102,103,104,105,106,107]. Analysis of the data grouped in Table 2 allowed us to identify more than 181 phytochemical compounds present in the Z. lotus extracts from different countries (Tunisia, Morocco, and Algeria). These phytochemicals encompass a significant number of fatty acids and four significant families of secondary metabolites including phenolic acids, terpenoids, flavonoids, and alkaloids (Table 2). The chemical structures of the main phytoconstituents present in Z. lotus extracts are presented in the figures according to their chemical classes, phenolic acids (Figure 2), flavonoids (Figure 3), terpenes (Figure 4), fatty acids (Figure 5), and alkaloids (Figure 6). In fact, in the methanol extract of the leaves, seeds, and fruits of Z. lotus from Tunisia, 28 phenolic compounds were found by Yassine et al. (2020) using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI–MS) analysis [19]. The authors of this study indicate that quinic acid, ferulic acid, epicatechin, rutin, quercitrin, naringin, and cinnamic acid are major phenolic compounds in this extract. In addition, 10 phenolic components including fumaric acid, catechin, tyrosol, gallic acid, syringic acid, p-coumaric acid, vanillin, ferulic acid, caffeic acid, and cinnamic acid were found in the methanol extract from Tunisian Z. lotus leaves using the high-performance liquid chromatography (HPLC) method [17]. Previous phytochemical studies have reported the identification of 15 different phytochemical compounds present in the methanolic extract of the fruits and leaves of Moroccan Z. lotus, namely galloyl shikimic acid, (-)-catechin 3-O-gallate, malic acid, quercetin, rhamnosyl-rhamnosylglucoside, quercetin di-glucoside, eriodictyol, macrocarpon C, amorfrutin A, isovitexin-2″-O-rhamnoside, hyperin, astragalin, 7,8-dihydrobiopterin, quercetin-3-galactoside, and kaempferol-3-diglucoside. According to other investigations, the aqueous extract of Moroccan Z. lotus fruits and leaves contains 22 distinct phenolic compounds including gallic acid, pyrogallol, chlorogenic acid, catechin, rutin, p-hydroxybenzoic acid, caffeic acid, vanillic acid, epicatechin, syringic acid, p-coumaric acid, 3-hydroxycinnamic acid, ferulic acid, sinapic acid, salicylic acid, rosmarinic acid, resveratrol, quercetin, naringin, catechol, hydroxytyrosol, and naringenin [20,21]. Other investigations have indicated that the aqueous extract of the branches and leaves of Algerian Z. lotus revealed the presence of 18 phenolic compounds, which were defined as quercetin-3-O-(2,6-di-O-rhamnosylglucoside)-7-O-rhamnoside, quercetin-3-O-(2,6-di-O-rhamnosylglucoside), myricetin-3-O-rutinoside, quercetin-3-O-(2,6-di-orhamnosylglucoside-7-O-glucuronide, kaempferol-3-O-(2,6-di-O-rhamnosylglucoside), phloretin-di-c-hexoside, quercetin-3-O-rutinoside, kaempferol-O-hexoside, kaempferol-3-O-(2,6-di-O-rhamnosylglucoside), oleuropein hexoside, kaempferol-3-O-rutinoside, kaempferol-3-O-(6-O-rhamnosyl-glucoside), apigenin-O-hexoside-O-deoxyhexoside, oleuropein, catechin, quercetin-O-deoxyhexoside, eriodictyol-O-deoxyhexoside, (Epi)catechin-(epi)gallocatechin, and (-)-epicatechin [26]. In addition, Ghedira et al. (1993, 1995) and Croueour et al. (2002) identified seven alkaloid compounds in the root bark extract of Z. lotus: lotusine A, lotusine D, lotusine B, lotusine C, lotusine E, lotusine F, and lotusine G [108,109,110].
Comparatively, we observed that the chemical composition of Z. lotus extracts varied from one country to another. This variation in the chemical composition between identical Z. lotus extracts from other countries may be provoked by a variety of elements including the collection’s origin, the climate during the harvest, the harvest season, and the extraction technique [111]. Letaief et al. (2021) studied the phytoconstituents of the essential oils from the aerial part of Tunisian Z. lotus using the gas chromatography-mass spectrometry (GC–MS) [107]. The authors of this investigation reported that the essential oil of Z. lotus contains 36 volatile compounds, with the major components being hexahydrofarnesyl acetone, followed by geranylacetone, cis-hexenyl-3-benzoate, 2-pentadecanone, dodecanoic acid ethyl ester, and n-hexadecanoic acid. In addition, Rais et al. (2020) showed the existence of fatty acids such as oleic acid, palmitic acid, stearic acid, and linoleic acid in the essential oil extracted from the seeds of Moroccan Z. lotus (Figure 3) [106]. Zazouli et al. (2022) studied the chemical composition of lipophilic fractions (dichloromethane extract) of different parts of the Moroccan Z. lotus using GC–MS (Table 2) [102]. A total of 99 lipophilic compounds including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic chemicals, sterols, monoglycerides, aromatic substances, and other minor substances were identified and measured in this recent study. In reality, it has been shown that the majority of lipophilic extracts of the pulp, leaves, and seeds are composed of fatty acids. Unsaturated fatty acids, specifically acid (9Z,12Z)-9,12-octadecadienoic acid (9Z)-9-octadecaenoic, were notably abundant in the leaves and seeds. The root bark, on the other hand, was rich in pentacyclic triterpenic substances, particularly betulinic acid.

7. Pharmacological Activities

Modern pharmacological research has revealed in recent years that Z. lotus extracts contain a range of pharmacological features including anti-diabetic, anti-cancer, hepatoprotective, nephroprotective, anti-inflammatory, analgesic, anti-oxidant, and antibacterial actions. Numerous studies have revealed that the chemical constituents and raw extracts of Z. lotus have significant levels of biological properties. Figure 7 provides an overview of the mechanisms of the pharmacological activities demonstrated by Z. lotus extracts.

7.1. Antidiabetic Activity

Numerous diabetic patients have employed conventional herbal treatments in a variety of formulations as a supplemental therapy to manage problems with diabetes since Antiquity [112,113]. As indicated in Table 1, the Z. lotus plant is frequently used in traditional medicine to treat diabetes. The anti-diabetic activities of these plant extracts have been confirmed by several preclinical studies on animals. In fact, an in vivo investigation discovered that giving diabetic hamsters an aqueous extract of Z. lotus fruit at a concentration of 300 mg/kg controlled the blood glucose levels [114]. The authors of this study indicated that the anti-diabetic activity of the aqueous extract of Z. lotus fruit (300 mg/kg) was comparable to that of the drug glucophage 50 mg (metformin). In addition, the effect of the Z. lotus leaf and fruit extract on the inhibition of α-amylase and α-glycosidase was evaluated in vitro [20]. The finding of this survey indicates that the Z. lotus leaf and fruit extract has potent in vitro anti-diabetic effects via α-amylase inhibition (leaves: IC50 = 20.40 ± 1.30 μg/mL; fruits: IC50 = 31.91 ± 1.53 μg/mL), and α-glycosidase (leaves: IC50 = 8.66 ± 0.62 μg/mL; fruits: IC50 = 27.95 ± 2.45 μg/mL). The effect of this extract was stronger to that of the common acarbose prescription. The data gathered from this text indicate the anti-diabetic potential of Z. lotus extracts, and support their traditional uses as anti-diabetic drugs.

7.2. Anti-Obesity and Dyslipidemic Activity

In recent years, hyperlipidemia has been considered as a major health illness. This factor is well-known to be the primary risk factor for the development of atherosclerosis as well as other related cardiovascular and brain vascular diseases [115]. Several previous investigations have been conducted to confirm the anti-hyperlipidemia activities of Z. lotus in the preclinical stage. Indeed, it has been demonstrated that the aqueous extract of Z. lotus fruits exerts anti-hyperlipidemic effects in albino mice fed a prolonged, fat-rich diet [35]. Results from this study indicate that the administration of the aqueous extract of Z. lotus fruit at 200 and 400 mg/kg for 30 days improved abnormal changes in the lipid profile (total cholesterol, HDL-cholesterol/total cholesterol, triglycerides, HDL-cholesterol, and atherogenic index) and blood glucose in albino mice subjected to a chronic high-fat diet. In addition, one study assessed the effects of Z. lotus fruits on diet-induced obesity in mice [116]. This study showed that taking 10% (w/w) of Z. lotus fruit powder supplemented with a high-fat diet for six weeks improved the plasma lipid concentrations, and thus the expression of key genes involved in energy metabolism and inflammation. In addition, an in vivo study demonstrated the anti-cholesterolemic effect of aqueous Z. lotus fruit extract in hamsters exposed to a high-fat diet [114]. Daily administration of an aqueous extract of Z. lotus fruit at a dose of 300 mg/kg in obese hamsters for 30 days substantially reduced the plasma level of bad cholesterol compared to obese animals not treated with the Z. lotus extract.

7.3. Antiulcerogenic and Anti-Spasmodic Activities

As indicated in Table 1, Z. lotus is utilized in herbal medicine in several countries to treat digestive tract pathologies such as constipation, diarrhea, and spasms. Several previous preclinical studies have shown the beneficial effects of Z. lotus extracts against some digestive problems. Bakhtaoui et al. (2014) showed that the administration of Z. lotus fruit methanol extract at 500 mg/kg had anti-ulcerogenic effects provoked by HCl/ethanol, pyloric ligature, and aspirin in Wistar rats [117]. Another study found that the oral administration of aqueous extracts of Z. lotus root bark, leaves, and fruits resulted in a substantial and dose-dependent inhibition of acute ulcers caused by the HCl/ethanol solution [118]. According to the same authors, this effect of Z. lotus extracts is comparable to that of cimetidine and omeprazole (standard drugs). Furthermore, the antispasmodic effects of aqueous and methanol extracts of Z. lotus leaves and root bark were tested on male rats [119]. The results of this investigation showed that Z. lotus root bark and leaf extracts were able to relax the tone of spontaneous duodenum contractions in rats and antagonize the spasmogenic effects caused by agonists such as acetylcholine, KCl, and BaCl2. The authors explain this effect by the fact that the extracts of Z. lotus clumped on the cholinergic receptors and blocked the influx of Ca2+.

7.4. Anti-Inflammatory and Immunomodulatory Activities

Inflammation is typically characterized as a reaction to an injury or infection [120]. It is now widely recognized that chronic inflammation is always linked to diseases of wealth and prolonged longevity including cancer, obesity, cardiovascular, and neurological disorders [120,121,122,123]. Inflammation is characterized by four primary symptoms: redness, heat, swelling, and pain. The body naturally responds to damaging stimuli by inducing inflammation, which is accomplished by the migration of plasma and leukocytes into damaged tissues. This particular immune response, which is categorized as acute inflammation, is crucial for the body to fend off dangerous microorganisms [124]. It is critical to identify chemicals that can aid in the resolution of inflammation in this situation in a way that is homeostatic, modulatory, effective, and well-tolerated by the body. In this context, a study revealed that Z. lotus extracts had an anti-inflammatory effect against carrageenan-caused edema in rats [29]. According to the findings of the study, administering an aqueous extract of the Z. lotus root bark intraperitoneally at doses of 50, 100, and 200 mg/kg significantly reduced the paw swelling caused by carrageenan three hours later by 37.81%, 69.18%, and 72.90%, respectively. Additionally, a considerable activity occurred at a dose of 200 mg/kg, three hours after the injection of carrageenan, after taking the methanolic extract, with a reduction of 67.57% in the volume of the paw. The authors of this study showed that this anti-inflammatory effect was close to that of the standard drugs (piroxicam). Furthermore, previous research indicates that extracts from various parts of Z. lotus have immunosuppressive properties. The methanolic extract of Z. lotus has the important property of modulating the changes in intracellular calcium concentrations caused by thapsigargine in human T Jurkat lymphocytes. It also has the ability to reduce the phosphorylation of the 1/2 kinase controlled by the extracellular signal (ERK1/2) as well as the proliferation of T-lymphocytes by slowing their progression from the S phase to the G2/M phase of the cell cycle and the expression of interleukin-2 (IL-2) [16]. Similarly, the aqueous extract of Z. lotus pulp, seeds, leaves, roots, and stems had a significant immunosuppressive effect, inhibiting the T lymphocyte proliferation [125].

7.5. Analgesic Activity

As a sensory modality, pain frequently serves as the sole indicator for the diagnosis of a number of disorders. It frequently serves a defensive purpose. Humans have employed a variety of therapies throughout history to relieve pain, with medicinal herbs standing out due to their widespread use [126]. In this regard, Borgi et al. (2007) reported that Z. lotus extracts have an analgesic activity in the preclinical stage [29]. In this investigation, it was shown that intraperitoneal injection of the aqueous, methanol, chloroform, and ethyl acetate extracts at doses of 50, 100, and 200 mg/kg caused a decrease in acetic acid-provoked writhing in mice. The same authors claimed that the analgesic effects of the ethyl acetate extract were extremely effective in comparison to the other tested extracts.

7.6. Anti-Cancer and Anti-Proliferative Activities

Cancer establishes when cells divide rapidly and invade the surrounding tissue before spreading to other parts of the body [127]. The key aim of anticancer therapy is to cure the illness while also attempting to extend and boost the quality of a patient’s condition [128]. Since chemotherapy has harmful effects on cancer treatment, alternative therapies based on bioactive cytotoxic substances are an important help in cancer prevention. Preclinical studies conducted using methanolic, aqueous, petroleum ether, dichloromethane, and acetonic extracts of Z. lotus have revealed the potential mechanisms of anticancer activity. Letaief et al. (2021) evaluated the cytotoxic activity of petroleum ether and dichloromethane extract from Z. lotus roots against the SH-SY5Yn cell line using the MTT assay [25]. The findings of this study indicate that all of these human neuroblast cells are very sensitive to extracts of petroleum ether and dichloromethane of the Z. lotus roots, with varying IC50 values after 24 h of treatment (IC50 = 184.413 ± 4.77 µg/mL), after 48 h of treatment (IC50 = 20.941 ± 1.16 µg/mL), and after 24 h of treatment (IC50 = 16.148 ± 0.93 µg/mL, and after 48 h of treatment (IC50 = 7.341 ± 1.98 µg/mL), respectively. Furthermore, Tlili et al. (2019) examined the cytotoxicity of an ethanolic extract of the aerial part of Z. lotus against two human cancer cell lines, colon carcinoma (CaCo-2) and myeloid leukemia (K-562) [104]. The results of this study showed that this extract inhibited the proliferation of CaCo-2 and K-562 with an IC50 below 50 μg/mL. Moreover, the Z. lotus root bark lipophilic extract displayed promising antiproliferative effects against MDA-MB-231, a triple negative breast cancer cell line, with an IC50 = 4.23 ± 0.18 µg/mL [102].

7.7. Hepato-Renoprotective Effects

Bencheikh et al. (2021), investigated the nephroprotective efficacy of an aqueous extract of Z. lotus fruits [21]. The authors utilized gentamicin (GM), an antibiotic aminoglycoside used to treat severe acute illnesses, to produce nephrotoxicity in rats, and examined the preventative efficacy of the aqueous extract of Z. lotus fruits as a result. GM caused a significant biochemical imbalance (an increase in blood urea, creatinine, and uric acid as well as a decrease in urine) and significant deterioration in renal function was evident in this imbalance. However, daily administration of the aqueous extract from Z. lotus fruits three hours prior to GM injection successfully restored these GM-induced defects. The plant extract’s efficacy was dose-dependent, with the highest effect reported at 400 mg/kg. These findings suggest the use of Z. lotus fruits as a nephroprotective agent due to their activities in improving the altered parameters during a nephrotoxicity condition [21]. In addition, Bencheikh et al. (2019) reported that Z. lotus fruits had hepatoprotective properties [22]. The authors utilized carbon tetrachloride (CCl4) as a toxic agent in this investigation to induce oxidative stress and hepatotoxicity in rats. This treatment led to a significant decrease (p < 0.001) in body weight as well as a large rise (p < 0.001) in the relative liver weight. Furthermore, the activity of plasma liver indicators (AST, ALT, and ALP) rose considerably (p < 0.001). It also had the ability to dramatically increase (p < 0.001) the concentration of direct and total plasma bilirubin as well as the levels of triglycerides (p < 0.05) among other liver biomarkers. Moreover, the authors assessed indicators of renal excretory function by assessing the plasma levels of creatinine, urea, and uric acid. Interestingly, the addition of the aqueous extract of Z. lotus fruits demonstrated substantial protection against CCl4-induced hepatotoxicity and nephrotoxicity. Indeed, the aqueous extract Z. lotus fruits restored almost all serum indicator enzymes and antioxidant status, bringing all values back to normal, indicating that the extract’s protective action in rats was mediated by reducing oxidative damage and liver injury [22]. The litholytic activity of the aqueous extracts of Z. lotus fruits and leaves was assessed in vitro and in silico [101]. Furthermore, the aqueous extract of Z. lotus fruits and leaves was found to suppress the production of CaOx crystals, induced by the addition of 0.1 mol/L oxalic acid in human urine, to form calcium oxalate (CaOx) crystals. The existence of bioactive chemicals detected by HPLC such as adenosine, isorhamnetin 3-O-rutinoside, p-hydroxybenzoic acid, and neoechinulin A was demonstrated by this litholytic action. In silico tests revealed that the discovered compounds work by targeting enzymes involved in calcium control, urate management, and acid–base homeostasis maintenance as well as having anti-inflammatory characteristics [101]. A study by Kouchalaa et al. (2017) evaluated the litholytic effects of the aqueous extract of Z. lotus on the dissolution of calcium oxalate and uric acid calculations in vitro [129]. The findings showed that at the end of the experiment, the ability of the aqueous extract to dissolve the calcium oxalate calculation was 7.65%, while the dissolution of the uric acid calculation was 10.75%. The high quantities of polyphenols and flavonoids in the extract were linked to the findings, according to the authors. Chakit et al. (2022) demonstrated that the aqueous extract of Z. lotus fruit had an anti-urolithic action in rats induced by ethylene glycol [130]. In the same ethylene glycol-induced urolithiatic model of rats, the administration of the aqueous extract of Z. lotus fruits dramatically decreased and prevented the formation of kidney stones and significantly alleviated renal impairment. The observed findings may be attributed to the tendency for urine alkalinization in Z. lotus fruit aqueous extract-treated mice is likely to have a role in oxalate crystal solubilization, which might potentially be one of the processes via which plant components act [130]. Calcium oxalate (CaOx) crystals were formed after the addition of 0.1 mol/L oxalic acid. The effect of aqueous extracts was compared to two reference antagonists (citrate and magnesium).

7.8. Antimicrobial Activity

Worldwide, bacterial diseases account for a significant portion of mortality and morbidity. Inappropriate and excessive use of antibiotics has resulted in the development of resistance, which is making treatment more difficult as antibiotic resistance rises [131]. Therefore, it has become more crucial than ever to create novel antibiotics that can withstand the array of bacterial resistance mechanisms. To this end, the intention has been focused in recent years on the search for natural-based new therapeutic agents, particularly medicinal plants. The latter could be a viable area for researching the capacity of natural antimicrobials to suppress and/or destroy bacteria [132]. In this direction, Z. lotus extracts have demonstrated antimicrobial effects against a wide range of bacteria, namely, Bacillus pumilus, Enterococcus faecalis, Listeria monocytogenes, Micrococcus luteus, Rhizobium sp., Staphylococcus aureus, Staphylococcus epidermidis, Agrobacterium sp., E. coli, Helicobacter pylori, Pseudomonas aeruginosa, and Salmonella Typhimurium and also show effects against two fungal strains (e.g., Candida albicans and Candida tropicalis).
Table 3 summarizes the antimicrobial properties of the Z. lotus extracts. Evidently, the acetonic extract of Z. lotus leaves had significant antibacterial activity against S. aureus, S. aureus methicillin-resistant, S. epidermidis, S. epidermidis methicillin-resistant, and L. monocytogenes, with the MIC ranging from 250 to 1000 µg/mL and MBC ranging from 500 to 2000 µg/mL [105]. Another study revealed that lipophilic extracts of various parts of Z. lotus have antibacterial potential against E. coli, S. aureus, and S. epidermidis strains, with MICs ranging from 1024 to 2048 µg/mL [102]. At a concentration of 10 mg/mL, the methanolic extract of Z. lotus leaves inhibits the growth of S. aureus, L. monocytogenes, S. typhimurium, and E. coli, with inhibition zones ranging from 10 to 13 mm [19]. Furthermore, the results of a study on ethanolic, methanolic, and aqueous extracts of Z. lotus seeds showed that these extracts have significant antibacterial activity against E. coli, P. aeruginosa, S. aureus, and E. faecalis with MICs ranging from 50 to 200 mg/mL [18]. Thus, the antimicrobial activity of the methanolic extract of Z. lotus stems was evaluated using the agar-well diffusion method against pathogenic microbial species S. aureus, E. coli, and P. aeruginosa [133]. The results of this study indicate a potential antibacterial activity of this extract with MIC values ranging from 6 to 7 mg/mL. In addition, the study of the antibacterial activity of the methanolic extract of Z. lotus fruits through the disc diffusion and micro-dilution method showed that this extract had an interesting activity against E. coli, Agrobacterium sp., Rhizobium sp., B. pumilus, and B. subtilis with a MIC range from 3.2 to 400 µg/mL [134]. Growth inhibition activities of Z. lotus leaf methanol extract against bacterial species, notably B. subtilis, S. aureus, E. coli, P. aeruginosa, S. Typhimurium, were assessed using the conventional paper disk test [135]. The findings of this study indicate that the Z. lotus leaf methanol extract inhibited bacterial growth with a MIC in the ranges of 12.5 to 1000 μg/mL.

7.9. Antioxidant Activity

An imbalance between the quantity of reactive oxygen species and free radicals, which have unpleasant side effects, and the body’s natural anti-oxidative defense mechanisms, results in oxidative stress [137,138]. In recent decades, researchers have concentrated on discovering naturally occurring anti-oxidizing chemicals that can counteract the potentially dangerous effects of free radicals [139]. In this respect, studies on the ability of Z. lotus extracts to bind free radicals have revealed that the various organs (twigs, leaves, fruits, seeds, and roots) have a notable anti-oxidative activity. The anti-oxidative capacity tests were performed using the DPPH, FRAP, TAC, β-carotene bleaching assay, and ABTS methods. The following table (Table 4) summarizes the results obtained in various countries throughout the world. Several studies have been conducted to assess the anti-oxidative potential of extracts from different parts of Z. lotus in Morocco, Algeria, Tunisia, and Italy. In Morocco, the anti-oxidant ability of the aqueous extract of Z. lotus fruits was found to be interesting with IC50 = 116 ± 0.02 µg/mL, and an important inhibition of β-carotene oxidation, 21.11% at 100 µg/mL, tested by the mean of DPPH and the β-carotene assays, respectively [35]. Aya et al. (2020) highlighted that the various extracts (namely, hexane, methanol, and dichloromethane extracts) of the fruits and the leaves of Z. lotus possessed an interesting DPPH radical scavenging ability, ranging from an IC50 equal to 0.70 mg/mL, and an IC50 >40 mg/mL, with the methanolic extract of Z. lotus leaves being the most potent antioxidant (IC50 = 0.70 mg/mL) among the other tested extracts [101]. Another report found that the methanolic, and ethanolic extracts from Z. lotus seeds expressed an anti-oxidant activity, corresponding to the IC50 = 1.33 ± 0.01 mg/mL, and IC50 = 1.32 ± 0.09 mg/mL, respectively [18]. A comparative study of the anti-oxidant abilities of the aqueous extract of Z. lotus fruits and leaves was conducted by [20] by the mean of three anti-oxidant methods (DPPH, ABTS, and FRAP). In this sense, the radical scavenging potential of the aqueous extract of the fruits was higher than that of the leaves in the three anti-oxidant assays, as shown in Table 4. The observed results were attributed to the high level of phenolics and flavonoid compounds in the fruits. Other Moroccan, Tunisian, Algerian, and Italian research teams have confirmed that the radical-scavenging ability is more important in Z. lotus fruits, regardless of the nature of the solvent. In this context, the crude methanol extract of Z. lotus fruits from Oued Esseder (southeastern Tunisia) showed an important scavenging effect against DPPH radicals with an IC50 = 15.15 ± 0.90 µg/mL as well as an important total antioxidant capacity of 25.02 ± 0.55 mg GAE/g EDW. The same results were obtained for the methanolic extracts of the fruits from Bengardane (southeastern Tunisia) [19]. Ait Abderrahim et al. (2017) examined the anti-oxidant capacity of the methanolic extract of Z. lotus stems in vitro using DPPH [133] and reported a remarkable anti-oxidant result of 480.20 ± 40.64 mg AAE/g EDW. An Italian team investigated the antioxidant effect of the methanolic extract of stem bark from Z. lotus (from Addaura, Palermo, Italy) using three different methods [140]. They recorded a strong capacity to chelate ferrous ions from the ferrozine complex (39.01 ± 4.30 mg ethylenediaminetetraacetic acid equivalents, EDTA/g extract). The tested extract exhibited a potent DPPH free radical-scavenging effect displayed by the equivalent of ascorbic acid (304.02 ± 4.80 mg AAE/g EDW). For the FRAP test, a strong lowering power in the FRAP test was observed (296.68 ± 1.81 mg TE/g EDW) [140].

7.10. Others Activities

Human skin enzymatic browning entails the production of melanin, which proceeds through numerous steps involving multiple enzymes [144]. Within these enzymes, tyrosinase is implicated in the first two steps, and its inhibition could be used to build skin-protective medicines. Inhibiting the tyrosinase activity is an essential skin protection approach. The dermatoprotective activity of the extracts of Z. lotus fruit and leaves was investigated in the work of Marmouzi et al. (2019) [20]. The aqueous extract of the Z. lotus fruits demonstrated a higher tyrosinase inhibitory activity than the leaf extract, with IC50 values of 70.23 ± 5.94 μg/mL and 129.11 ± 9.40 μg/mL, respectively. Both extracts were more effective than the reference substance utilized (quercetin) with 246.90 ± 1.90 µg/mL. The difference in inhibitory activities between the Z. lotus fruit and leaf extracts is mostly related to chemical functional component differences. The extract of Z. lotus fruits is high in phenolic components such as catechin, gallic acid, and rutin. These substances are recognized tyrosinase inhibitors [144].
Khazri et al. (2017) evaluated the neuroprotective effect of the Z. lotus fruit extract against the neurotoxicity-induced by cypermethrin (CYP), a synthesized pyrethroid employed as an insecticide in large-scale agricultural applications [145]. CYP administration in mice resulted in a substantial increase (p < 0.05) in the heart, liver, and kidney oxidative markers (H2O2 and catalase) as well as an increase (p < 0.001) in the MDA levels in the heart, liver, and kidney. The current study also found that once 150 µg/L of CYP administered to mice significantly inhibited the AChE activity, when referred to healthy mice, this decrease (p < 0.05) in AChE activity was observed in all organs. The administration of the Z. lotus fruit extract successfully preserved standard biochemical parameters in mice against the toxicity generated by CYP. These findings support the pharmacological efficacy of the Z. lotus fruit extract in CYP-induced oxidative stress, suggesting the use of the extract as a neuroprotective agent

8. Toxicology

The plant’s security was proposed by its widespread use as a food and in ethnomedicine for a range of ailments, with no mentioned harmful effects. Bencheikh et al. (2019) investigated the acute oral toxicity of the aqueous extract of Z. lotus fruit in mice. After 14 days of observation, they found that a single oral dosage of this extract at 2000 mg/kg body weight did not cause any animal fatalities or changes in animal behavior [22]. Bekkar et al. (2021) found that a single dose of 5000 mg/kg body weight did not exhibit a toxic effect, death, or change in behavior after 14 days [23]. According to the findings of this plant’s acute toxicity, an acute use of this plant could be safe. To validate the safety of the long-term application of Z. lotus species, more studies on sub-chronic and chronic toxicity assessment should be carried out.

9. Concluding Remarks and Future Prospects

We emphasized the studies on the ethnobotanical, phytochemical, toxicological, and pharmacological properties of Z. lotus in this review. Several countries, especially those in North Africa, employ this plant extensively in herbal medicine to cure a broad range of illnesses including diabetes, digestive system issues, urinary tract issues infectious diseases, cardiovascular disorders, neurological diseases, skin issues, and others. According to the most recent pertinent data, several bioactive substances have been identified and isolated from Z. lotus extracts. These chemicals are secondary metabolites that belong to the flavonoids, phenolic acids, terpenoids, alkaloids, and other classes. In various scientific studies, the pharmacological assessment of Z. lotus revealed interesting medicinal activities. Indeed, Z. lotus fruit was observed to be the most efficient component of the plant in terms of treating diabetes, obesity, dyslipidemia, ulcers, and spasms. Additionally, it was found to have an anti-urolithic effect, preventing the formation of kidney stones. Furthermore, Z. lotus fruits showed significant protective effects against both CCl4-induced hepatotoxicity and GM-induced nephrotoxicity in rats. It was found that the fruit extract of Z. lotus demonstrated a higher inhibitory activity against tyrosinase compared to the leaf extract. For the neuroprotective effect of the plant against neurotoxicity induced by CYP, the Z. lotus fruit extract helped preserve standard biochemical parameters in mice against the toxicity generated by CYP, suggesting the potential use of the extract as a neuroprotective agent. The fruits and leaves also exhibited the ability to inhibit the production of CaOx crystals, induced by the addition of oxalic acid in humans. Research has demonstrated that the root bark of Z. lotus possesses properties that can help to reduce inflammation, and has immunosuppressive abilities as it can regulate intracellular calcium levels and reduce T-lymphocyte proliferation. Regarding the antimicrobial activity, all parts of the plant including the leaves, stems, seeds, and fruits displayed noteworthy antibacterial activity against a variety of bacterial strains including S. aureus, E. coli, and P. aeruginosa. However, the efficacy of each part may vary depending on the specific bacteria and extraction method used. Several studies have shown that different parts of the Z. lotus plant such as twigs, leaves, fruits, seeds, and roots possess significant antioxidant properties. The antioxidant capacity of these extracts was tested using various methods such as DPPH, FRAP, TAC, β-carotene bleaching assay, and ABTS, which demonstrated varying levels of antioxidant activity. These in vivo and in vitro pharmacological confirmations confirm the traditional uses of Z. lotus extracts. However, the studies on the pharmacological properties discussed in this paper did not show the underlying pathways by which Z. lotus extracts act. Using data from the literature, some studies suggest a positive relationship between pharmacological properties and some of the isolated Z. lotus compounds in some bioactivities. To fully understand the mechanism of action of the bioactive compounds found in Z. lotus, additional study on this topic is necessary. The toxicological testing of Z. lotus extracts on animal models revealed no significant acute toxicity. However, further research is required to assess the toxicity at various dosages and over various time periods. Clinical investigations are urgently required to support the usage of this herb since controlled trials were not performed.

Author Contributions

Conceptualization, N.B., S.O. and M.E.; Methodology, N.B., M.O., F.Z.R. and I.O.; Software, M.B. and A.E.; Validation, N.B., M.E. and C.H.; Formal analysis, M.O., N.B., J.F., F.Z.R. and S.O.; Investigation, N.B., M.B., I.O., J.F. and F.Z.R.; Resources, C.H.; Data curation, M.O., A.E., I.O. and J.F.; Writing—original draft preparation, N.B., S.O. and A.E.; Writing—review and editing, C.H., M.B., N.B. and M.E.; Visualization, C.H., N.B. and M.E; Supervision, M.E.; Funding acquisition, C.H. All authors have read and agreed to the published version of the manuscript.

Funding

Part of this study was funded by Conseil Départemental d’Eure-et-Loir.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors would like to thank Loubna Kharchoufa and Hayat Ouassou for the linguistic verification of this manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviation

LC-ESI–MS: liquid chromatography-electrospray ionization-tandem mass spectrometry, GC-MS: gas chromatography-mass spectrometry, HPLC: high-performance liquid chromatography, MTT assay: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, GM: gentamicin, CCl4: carbon tetrachloride, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase, Z. lotus: Ziziphus lotus (L.) Lam., CaOx: calcium oxalate, CaCo-2: carcinoma, K-562: myeloid leukemia, MIC: minimum inhibitory concentration, MBC: minimum bactericidal concentration, DPPH: 2-2-diphenyl-1-picrylhydrazyl; FRAP: ferric reducing/antioxidant power; TAC: total antioxidant capacity; ABTS: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); TE: Trolox equivalent; EDW: extract dry weight; AAE: ascorbic acid equivalent; GAE: gallic acid equivalent; EDTAE: ethylenediaminetetraacetic acid equivalent; IC50: median inhibitory concentration, ERK1/2: 1/2 kinase controlled by the extracellular signal, IL-2: interleukin-2, MTT assay: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA: deoxyribonucleic acid, CYP: cypermethrin.

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Pharmaceuticals 16 00575 g001 550
Figure 1. (A) Global view of Z. lotus. (B) Leaves of Z. lotus in the flowering stage. (C) Z. lotus fruits in ripening phase. (D) Mature Z. lotus fruits.
Figure 1. (A) Global view of Z. lotus. (B) Leaves of Z. lotus in the flowering stage. (C) Z. lotus fruits in ripening phase. (D) Mature Z. lotus fruits.
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Figure 2. Chemical structures of the main phenolic compounds detected in the Z. lotus extracts.
Figure 2. Chemical structures of the main phenolic compounds detected in the Z. lotus extracts.
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Figure 3. Chemical structures of the main flavonoid compounds found in the Z. lotus extracts.
Figure 3. Chemical structures of the main flavonoid compounds found in the Z. lotus extracts.
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Figure 4. Chemical structures of the terpene compounds detected in the Z. lotus extracts.
Figure 4. Chemical structures of the terpene compounds detected in the Z. lotus extracts.
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Figure 5. Chemical structures of the fatty acids identified in Z. lotus.
Figure 5. Chemical structures of the fatty acids identified in Z. lotus.
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Figure 6. Chemical structures of the alkaloid compounds identified in Z. lotus.
Figure 6. Chemical structures of the alkaloid compounds identified in Z. lotus.
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Figure 7. Comprehensive summary of the pharmacological activities of Z. lotus.
Figure 7. Comprehensive summary of the pharmacological activities of Z. lotus.
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Table
Table 1. Ethnobotanical uses of Z. lotus.
Table 1. Ethnobotanical uses of Z. lotus.
CountryRegionVernacular NameParts UsedMode of PreparationMode of AdministrationTherapeutic UsesReference
Morocco NortheasternAsadra, Nbeg, Tazakort Leaves, seedsDecoction, raw, or freshOralDigestive problems, skin problems, nervous system disorders, diabetes, urinary tract problems, endocrine and metabolic disorders, and muscles diseases [8]
Northeastern Morocco including eight province districts-Flowers, leaves, roots Decoction, infusion, powder-Diabetes, urinary infections, antispasmodic, kidney diseases, hair care, circulatory disorders, and respiratory problems[9]
Region of Fez-MeknesNbeg Fruits, leavesDecoction-Kidney stones[37]
High Atlas Central MoroccoSsedra,
Azgour 		Fruits, leaves Decoction powder-Antiulcer, antidiarrheal, anorexia[55]
High Atlas Central of MoroccoSsedra,
Azgour 		Fruits, leaves Decoction, infusion, powder-Antidiarrheal, promotes the healing of wounds, antiulcer, aperitif, antidiabetic, [38]
High Atlas Central of MoroccoSsedra,
Azougar		Fruits, leaves, rootsDecoction, infusion, powder-Diabetes[55]
Middle Oum RbiaSdar,
Nbeg		Fruits, leaves, seeds--Digestive, dermatological, genitourinary, cardiovascular, metabolic[56]
Guercif ProvinceSadraRootsMaceration-Diabetes, intestinal pain[57]
Northeastern MoroccoAsadra,
Nbeg 		Leaves, fruits, rootsDecoction, infusion, powderOralUrine retention, diuretic, renal colic, pyelonephritis, polycystic kidney disease, and kidney stones[36]
Markets of Salé Prefecture, Northwestern MoroccoSedr -Decoction-COVID-19[58]
Rif, Northern MoroccoNbeg,
Tazart		Seeds--Digestive system disorders[59]
Region of Tadla AzilalNbegFruits, leavesPowder-Gastrointestinal disorder[60]
Rabat-Sale-KenitrNbegFruits, leavesDecoction-Chronic kidney diseases[61]
TazaSadra Fruits, leavesInfusion, powder Externally, oralKidney problems, digestive system, diabetes, antimicrobial, hair care[62]
Moulay Yacoub RegionAsadra FruitsInfusion, powderOralStomach ache, hair care[63]
Tarfaya ProvinceSeder Leaves Powder OralKidney stones[64]
Province of TarfayaSsder Fruits, leavesPowder, poulticeOral, externallyKidney stones, stomach pain, hair loss[65]
Province of Sidi KacemSsedra SeedsRaw-Digestive infection[66]
Region of Fez-MeknesSidra, NbegSeedsDecoction, -Acute ache, digestion problems, intestinal comfort, bloating[67]
Er-Rich regionAzouggarFruitsPowder-Stomach pain, colon pain, anemia[68]
Nador ProvinceThazagorth, SidraFruits, leaves Decoction; powder-Digestive diseases, diabetes[69]
Northeastern of MoroccoSedraLeaves, stemsInfusionOralHeadache, joint pain[70]
Province of TaroudantAzougar, Sedr, NbegRootsInfusionOralDiabetes[71]
Northeastern MoroccoSedr, Nbeg Roots--Digestive disease, diabetes[72]
-Nbague Fruits Decoction, infusion OralKidney stones [73]
Region of Fez-MeknesSidra, Nbeg SeedsDecoction Diabetes, kidney problems [74]
Taza RegionNbeg LeavesDecoction, powder-Diabetes[75]
Agadir Ida Outanane regionAzegar, Sedra, NbegSeeds Decoction-Diabetes[39]
AlgeriaEl-BayadhSedra LeavesDecoctionExternally use, internally use Antitussive, antiseptic[40]
Region of Ouargla-Fruits, leaves, rootsDecoction, maceration-Anti-inflammatory, moisturizer, sedative, diuretic[47]
Tlemcen-RootsDecoctionOralDiabetes[41]
The region of Hodna (M’Sila)SedraLeavesInfusion-Eczema[44]
North and southwestern AlgeriaSadraLeavesDecoction-Diabetes mellitus[76]
Region of TiaretSedra---Pulmonary affections[77]
M’Sila (North Algeria)Sedra LeavesDecoction, infusion, powder-Anti-inflammatory, wound-healing, dermal eczema[78]
Djebel Messaad Region (M’Sila, Algeria)-Fruits, leaves, rootsDecoction-Anti-inflammatory, emollient, pectoral [43]
M’SilaSedra LeavesBath, infusion, lotion-Hair loss[79]
Djebel Zdimm (Setif)-Fruits, leaves, seeds--Stomach acidity, hypertension[80]
Hoggar, AlgeriaTabakat Fruits, leaves Decoction, powder-Digestive diseases, diarrhea, diabetes[81]
Southeast of the capital of Hodna (Algeria)Sedra LeavesLotion-Fever, eye diseases[82]
Oued Righ (Algerian Sahara) Nbak, Sedra Fruits, leaves, rootsDecoction, maceration-Tonic, emollient, sedative, anti-inflammatory, pectoral, diuretic[46]
RootsDecoction-Gastrointestinal tract diseases, liver diseases
Fruits--Respiratory system
Adrar and Bechar RootsInfusionOralDiabetes[83]
FruitsDecoction, raw-Renal disorders
-Decoction -Infections
Raw-Hair loss
West of Bordj Bou Arreridj (El Mansourah), AlgeriaSedra Fruits, rootsPowder, raw-Pectoral, emollient activity, hepatic, chlorosis, lungs diseases, jaundice[84]
Algerian Semi-Arid Region E’ssedra Fruits, leaves, roots --Measles, constipation, diuretic, hair care, heart diseases, hyperglycemia, renal pain, renal stones, stomach ache, urinary infections[85]
East of AlgeriaEssedra LeavesInfusion-Skin, digestive[86]
Region of BissaSedraRootsDecoctionWhite washingToothache[87]
Northeast Sedra RootsPowder, raw-Pulmonary affections, jaundice[88]
Northeastern AlgeriaSedraAerial parts, roots Infusion-Diabetes[89]
Region of AuresThazzgarth FruitsDecoction used in mixture with honey, and Algerian tea-Urinary calculus[90]
Southeast of M’Sila (rural communities of Ben Srour)SadraFruits, leaves, roots Cataplasm, powder, raw-Pulmonary affections, jaundice, eczema, emollient, stomach pain, headache[91]
Tlemcen National Park (extreme northwest of Algeria)Essadra Leaves, rootsDecoctionOralStomach ache, colon, body pain, arthritis[42]
El Hammadia regionSedra ---Lungs diseases, jaundice, emollient[91]
El KantaraSedra, Nebag Fruits, leaves Chewing, decoction-Heartburn, constipation, weakness of heart, diuretic, breastfeeding[92]
Northwestern of Algeria Sedra LeavesPowder with honey-Breast cancer[93]
Algerian Central Steppe Region (Djelfa)Sedra Leaves, rootsDecoction, lotion, maceration -Insomnia, renal diseases, hydatid cysts[94]
Region of Tiaret, Northwest of Algeria SedraFruits, leaves, rootsDecoction, infusionOralAll reported ailments[95]
MauritaniaAdrar ProvinceSdar hreytekAerial parts, fruitsChewing, infusion, powderOralAbdominal pain, epigastric[48]
LeavesMacerated white water Fever
Powder, macerationOralHypertension
InfusionOralNon-insulin dependent diabetes
FruitsPowderOralKidney symptoms
Libya Al-Jabal Al-Akhder, Wadi Alkuf, LibyaSidr, Nabq ---Hair parasites, sciatica, abscess, piles, hepatitis, gastritis, constipation[50]
Northeastern regionSidr, Nabq Barks fruits, leaves, roots --Hair parasites, gastritis, sciatica, abscess, reinforcement and activation of piles hepatitis, psychiatric and spiritual counseling abdominal issues, constipation[51,96]
JordanThe central mountains (North–South) in JordanSader, Orkod FruitsEdible-Cough and measles[52]
Jordan (countryside, and desert)Ceder Fruits, seedsDecoction-Vermifuge and antispasmodic[53]
--Bark, branches, gum, leaves, root Powder-Toothache[97]
LeavesPowder-Cleaning dead bodies. Women utilize leaf powder, which works extremely well as shampoo, in combination with hot water to wash their hair.
Decoction-Head lice
--Treat dandruff and counter obesity
---Anti-diabetic, antibacterial, anti-cancer, anti-hypertensive, anti-nociceptive, anti-diarrheal, intestinal ailments, colds, and skin.
Palestine West BankLotus jujube, zyzafunLeavesDecoction-Diarrhea[98]
CyprusNorth CyprusGonnaraFruitsRaw--[99]
NigeriaKebbi State (northwest)TsadaBark, root --Cancer[100]
Table
Table 2. Phytoconstituents of the Z. lotus extracts.
Table 2. Phytoconstituents of the Z. lotus extracts.
CountryUsed PartUsed ExtractChemical CompoundsReferences
TunisiaRootsPetroleum ether extractEthyl tridecanoate; 2-pentadecanone; pentadecanoic acid, ethyl ester; 13-epimanool; tetradecanoic acid; n-hexadecanoic acid[25]
Dichloromethane extractEthyl tridecanoate; tetradecanoic acid, ethyl ester; 13-epimanool
LeavesMethanol extractLuteolin; trans cinnamic acid; quercetin; rutin; gallic acid; syringic acid; 4-O-caffeoylquinic acid; epicatechin; trans-ferulic acid; hyperoside; p-coumaric acid; quercitrin; naringin; kaempferol; naringenin; apigenin; acacetin; quinic acid; (+)-catechin [19]
FruitsQuinic acid; luteolin-7-O-glucoside; rutin; epicatechin; p-coumaric acid; apigenin-7-O-glucoside; quercitrin; naringin; chlorogenic acid; 1,3-di-O-caffeoylquinic acid; cirsilineol
SeedsQuinic acid; catechin (+); 4,5-di-O-caffeoylquinic acid; chlorogenic acid; syringic acid; hyperoside; rutin; 3,4-di-O-caffeoylquinic acid; quercitrin; naringin; apigenin-7-O-glucoside; 4-O-caffeoylquinic acid; trans cinnamic acid; quercetin; p-coumaric acid; luteolin; naringenin; apigenin
Leaves, and flowersEssential oil Nonanal; decanal; linalool; α-cadinol; azulol; farnesyl acetone; 2-undecanone; 2-pentadecanone; tetradecanoic acid, ethyl ester; α-farnesene; carvone; γ-cadinene; tridecanal; trans-β-ionone; D-nerolidol; E-nerolidol; hexyl-benzoate; hexahydrofarnesyl acetone; cis-hexenyl-3-benzoate; cadalene; dodecanoic acid; tetradecanoic acid; decanoic acid, ethyl ester; undecanoic acid, ethyl ester; 2-tridecanone; β-cyclocitral; L-α-terpineol; dodecanoic acid, ethyl ester; ethyl tridecanoate; ledol; pentadecanoic acid, ethyl ester; hexadecanoic acid, ethyl ester; damascenone; geranylacetone; α-calacorene[107]
FruitsMethanolic extractLauric acid; myristic acid; pentadecyclic acid; palmitic acid; heptaguaric acid; oleic acid; elaidic acid; linoleic acid; α-linolenic; stearidonic acid; arachidic acid; behenic acid; erucic acid[27]
LeavesMethanolic extractFumaric acid; catechin; tyrosol; gallic acid; syringic acid; p-coumaric acid; vanillin; ferulic acid; caffeic acid; cinnamic acid[17]
LeavesAcetonic extractRutin; luteolin-7-O-glucoside; naringin; luteolin; kaempferol[105]
LeavesAcetonic extractQuinic acid; gallic acid; protocatchuic acid; catechin (+); quercetin-3-O-galactoside; 4-O-caffeoylquinic acid; syringic acid; epicatechin; p-coumaric acid; rutin; quercetin-3-O-rhamonoside; quercetin; kaempherol; naringenin; apegenin; luteolin[104]
Root barkClassical acid–base method (Alkaloid extract)Lotusine A; lotusine D[110]
Root barkClassical acid–base method (Alkaloid extract)Lotusine B; lotusine C; lotusine E; lotusine F[109]
Root barkClassical acid–base method (Alkaloid extract)Lotusine G[108]
MoroccoSeedsEssential oilOleic acid; palmitic acid; linoleic acid; stearic acid[106]
FruitsEthanol extractSynapic acid; benzoic acid; p-coumaric acid; p-hydroxybenzoic acid; p-coumaroyl glucose; cinnamic acid derivative[24]
Methanol extractMalic acid; (-)-catechin 3-O-gallate; quercetin; galloyl shikimic acid; quercetin di-glucoside; rhamnosyl-rhamnosylglucoside; eriodictyol
LeavesAqueous extractGallic acid; catechin; rutin; p-hydroxybenzoic acid; caffeic acid; vanillic acid; epicatechin; resveratrol; syringic acid; p-coumaric acid; 3-hydroxycinnamic acid; pyrogallol; salicylic acid; naringin; ferulic acid; chlorogenic acid; sinapic acid; rosmarinic acid; quercetin[20]
FruitsGallic acid; chlorogenic acid; catechin; rutin; p-hydroxybenzoic acid; 3-hydroxycinnamic acid; vanillic acid; epicatechin; caffeic acid; syringic acid; p-coumaric acid; ferulic acid; pyrogallol; sinapic acid; naringin; salicylic acid; rosmarinic acid; resveratrol; catechol
FruitsMethanolic extractMacrocarpon C; isovitexin-2″-O-rhamnoside; amorfrutin A; hyperin; astragalin[101]
Leaves7,8-Dihydrobiopterin; quercetin-3-galactoside; kaempferol-3-diglucoside
PulpDichloromethane extractDecanoic acid; tridecanoic acid; tetradecanoic acid;; heptadecanoic acid; octadecanoic acid; nonadecanoic acid; eicosanoic acid; heneicosanoic acid; hexacosanoic acid; heptacosanoic acid; octacosanoic acid; triacontanoic acid; tetradecenoic acid; hexadecenoic acid; heptadecenoic acid; (9Z,12Z)-octadeca-9,12-dienoic acid; (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid; (9Z)-octadec-9-enoic acid; (9E)-octadec-9-enoic acid; nonadecenoic acid; pentadecanoic acid; hexadecanoic acid; undecanoic acid; dodecanoic acid; eicos-11-enoic acid; hexadecanedioic acid; 22-hydroxydocosanoic acid; 2-hydroxytetracosanoic acid; ethyl decanoate; ethyl tetradecanoate; ethyl pentadecanoate; ethyl hexadec-9-enoate; docosanoic acid; pentacosanoic acid; ethyl hexadecanoate; ethyl (9Z)-octadec-9-enoate; ethyl (9E)-octadec-9-enoate; ethyl octadecanoate; ethyl eicosanoate; methyl hexadecanoate; 1-palmitoylglycerol; 1-oleoylglycerol; hexadecan-1-ol; (9Z)-octadec-9-en-1-ol; oleanolic acid; betulinic acid; ursolic acid; stigmasterol; β-sitosterol; benzoic acid; vanillic acid; p-coumaric acid; solerol; glycerol; octacosanal; nonacosan-10-one; triacontanal[102]
SeedsDecanoic acid; dodecanoic acid; tetradecanoic acid; pentadecanoic acid; hexadecanoic acid; heptadecanoic acid; octadecanoic acid; eicosanoic acid; docosanoic acid; hexadecenoic acid; heptadecenoic acid; (9Z,12Z)-octadeca-9,12-dienoic acid; (9Z)-octadec-9-enoic acid; (9E)-octadec-9-enoic acid; eicos-11-enoic acid; ethyl hexadecanoate; ethyl (9Z)-octadec-9-enoate; methyl (9Z)-octadec-9-enoate; 2-palmitoylglycerol; 1-palmitoylglycerol; 1-linoleoylglycerol; 1-oleoylglycerol; 1-stearoylglycerol; hexadecan-1-ol; oleanolic acid; betulinic acid; ursolic acid; stigmasterol; β-sitosterol; benzoic acid; vanillin; vanillyl alcohol; E-ferulic acid; glycerol; squalene
LeavesDecanoic acid; dodecanoic acid; hexadecanoic acid; heptadecanoic acid; octadecanoic acid; eicosanoic acid; heneicosanoic acid; docosanoic acid; tetracosanoic acid; pentacosanoic acid; octacosanoic acid; hexadecenoic acid; (9Z,12Z)-octadeca-9,12-dienoic acid; tetradecanoic acid; pentadecanoic acid; (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid; (9Z)-octadec-9-enoic acid; (9E)-octadec-9-enoic acid; eicos-11-enoic acid; 22-hydroxydocosanoic acid; 2-palmitoylglycerol; 1-palmitoylglycerol; 1-linoleoylglycerol; 1-linolenoylglycerol; 1-stearoylglycerol; hexadecan-1-ol; (9Z)-octadec-9-en-1-ol; octadecan-1-ol; lupeol; oleanolic acid; betulinic acid; campesterol; β-Sitosterol; benzoic acid; salicylic acid; vanillic acid; p-coumaric acid; glycerol; loliolide; neophytadiene; inositol; phytol; squalene; γ-tocopherol; tetracosyl acetate; α-tocopherol
Root BarkDecanoic acid; dodecanoic acid; heptadecanoic acid; nonadecanoic acid; eicosanoic acid; docosanoic acid; tetracosanoic acid; pentacosanoic acid; hexadecenoic acid; heptadecenoic acid; (9Z,12Z)-octadeca-9,12-dienoic acid; (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid; (9Z)-octadec-9-enoic acid; octadecanoic acid; (9E)-octadec-9-enoic acid; eicos-11-enoic acid; 22-hydroxydocosanoic acid; tricosanoic acid; heneicosanoic acid; methyl (9Z)-octadec-9-enoate; 1-palmitoylglycerol; 1-linoleoylglycerol; pentadecanoic acid; hexadecanoic acid; 1-oleoylglycerol; 1-stearoylglycerol; tetradecan-1-ol; hexadecan-1-ol; octadecan-1-ol; lupeol; oleanolic acid; betulinic acid; campesterol; stigmasterol; β-Sitosterol; vanillin; vanillyl alcohol; syringaldehyde; homovanillyl alcohol; vanillic acid; hydroxytyrosol; protocatechuic acid; syringic acid; glycerol
FruitsAqueous extract3-hydroxycinnamic acid; catechin; hydroxytyrosol; naringenin; p-coumaric acid; quercetin; rutin; vanillic acid; ferulic acid; gallic acid[21]
AlgeriaBranchesDecoctionCatechin; quercetin-3-O-rutinoside; apigenin-O-hexoside-O-deoxyhexoside; eriodictyol-O-deoxyhexoside; oleuropein; quercetin-O-deoxyhexoside; oleuropein hexoside [26]
InfusionCatechin; quercetin-3-O-rutinoside; apigenin-O-hexoside-O-deoxyhexoside; eriodictyol-O-deoxyhexoside; oleuropein; quercetin-O-deoxyhexoside; oleuropein hexoside
Hydroethanolic extractCatechin; quercetin-3-O-rutinoside; oleuropein hexoside; apigenin-O-hexoside-O-deoxyhexoside; eriodictyol-O-deoxyhexoside; oleuropein; quercetin-O-deoxyhexoside
LeavesDecoctionQuercetin-3-O-(2,6-di-O-rhamnosylglucoside)-7-O-rhamnoside;
myricetin-3-O-rutinoside; quercetin-3-O-(2,6-di-orhamnosylglucoside-7-O-glucuronide; kaempferol-3-O-(2,6-di-o rhamnosylglucoside); phloretin-di-c-hexoside; kaempferol-O-hexoside; kaempferol-3-O-(2,6-di-O-rhamnosylglucoside); oleuropein hexoside; kaempferol-3-O-rutinoside; kaempferol-3-O-(6-O-rhamnosyl-glucoside); apigenin-O-hexoside-O-deoxyhexoside; quercetin-3-O-rutinoside; oleuropein; quercetin-3-O-(2,6-di-O-rhamnosylglucoside)
InfusionQuercetin-3-O-(2,6-di-O-rhamnosylglucoside)-7-O-rhamnoside; apigenin-O-hexoside-O-deoxyhexoside; myricetin-3-O-rutinoside; quercetin-3-O-(2,6-di-orhamnosylglucoside-7-O-glucuronide; kaempferol-3-O-(2,6-di-O-rhamnosylglucoside); phloretin-di-c-hexoside; quercetin-3-O-rutinoside; quercetin-3-O-(2,6-di-O-rhamnosylglucoside); kaempferol-O-hexoside; kaempferol-3-O-(2,6-di-O-rhamnosylglucoside); oleuropein hexoside; kaempferol-3-O-rutinoside; kaempferol-3-O-(6-O-rhamnosyl-glucoside); oleuropein
Hydroethanolic extractQuercetin-3-O-(2,6-di-O-rhamnosylglucoside)-7-O-rhamnoside; myricetin-3-O-rutinoside; quercetin-3-O-(2,6-di-orhamnosylglucoside-7-O-glucuronide; kaempferol-3-O-(2,6-di-O-rhamnosylglucoside); phloretin-di-c-hexoside; quercetin-3-O-rutinoside; kaempferol-O-hexoside; kaempferol-3-O-(2,6-di-O-rhamnosylglucoside); oleuropein hexoside; kaempferol-3-O-rutinoside; kaempferol-3-O-(6-O-rhamnosyl-glucoside); apigenin-O-hexoside-O-deoxyhexoside; oleuropein; quercetin-3-O-(2,6-di-O-rhamnosylglucoside)
Root barksDecoction(Epi)catechin-(epi)gallocatechin; (+)-catechin; (-)-epicatechin; myricetin-3-O-rutinoside
Infusion(Epi)catechin-(epi)gallocatechin; (-)-epicatechin; myricetin-3-O-rutinoside
Hydroethanolic(Epi)catechin-(epi)gallocatechin; (+)-Catechin; (-)-Epicatechin; Myricetin-3-O-rutinoside
Stem barksDecoctionOleoside; eriodictyol-O-hexoside; quercetin-O-deoxyhexoside; eriodictyol-O-pentoside; eriodictyol-O-deoxyhexoside; eriodictyol-O-deoxyhexoside
InfusionOleoside; quercetin-O-deoxyhexoside; eriodictyol-O-pentoside; eriodictyol-O-deoxyhexoside; eriodictyol-O-deoxyhexoside
HydroethanolicOleoside; eriodictyol-O-hexoside; quercetin-O-deoxyhexoside; eriodictyol-O-pentoside; eriodictyol-O-deoxyhexoside; eriodictyol-O-deoxyhexoside
Table
Table 3. The antimicrobial results of the Z. lotus extracts.
Table 3. The antimicrobial results of the Z. lotus extracts.
Used PartsExtractsBacteria or Fungi (Concentration)References
LeavesAcetonic extractS. aureus (MIC = 1000 µg/mL; MBC = 2000 µg/mL), S. aureus methicillin-resistant (MIC = 250 µg/mL; MBC = 2000 µg/mL), S. epidermidis (MIC = 250 µg/mL; MBC = 500 µg/mL), S. epidermidis methicillin-resistant (MIC = 500 µg/mL; MBC = 1000 µg/mL), L. monocytogenes (MIC = 500 µg/mL; MBC = 2000 µg/mL)[105]
PulpsLipophilic extractE. coli (MIC >2048 µg/mL), S. aureus (MIC >2048 µg/mL),
S. epidermidis (MIC > 2048 µg/mL)		[102]
SeedsE. coli (MIC >2048 µg/mL), S. aureus (MIC >2048 µg/mL),
S. epidermidis (MIC = 1024 µg/mL)
LeavesE. coli (MIC = 1024 µg/mL), S. aureus (MIC = 2048 µg/mL),
S. epidermidis (MIC = 1024 µg/mL)
Root barkE. coli (MIC >2048 µg/mL), S. aureus (MIC = 2048 µg/mL),
S. epidermidis (MIC = 2048 µg/mL)
LeavesMethanolic extractS. aureus (10 mg/mL; IZ = 12–13 mm), L. monocytogenes (10 mg/mL; IZ = 10–12.2 mm), S. typhimurium (10 mg/mL; IZ = 11–12.2 mm), E. coli (10 mg/mL; IZ = 10.6–11.8 mm)[19]
SeedsEthanolic extractE. coli (MIC = 50 mg/mL), P. aeruginosa (MIC = 50 mg/mL),
S. aureus (MIC = 100 mg/mL), E. faecalis (MIC = 50 mg/mL)		[18]
Methanolic extractE. coli (MIC = 100 mg/mL), P. aeruginosa (MIC = 50 mg/mL),
S. aureus (MIC = 100 mg/mL), E. faecalis (MIC = 50 mg/mL)
Aqueous extractE. coli (MIC = 200 mg/mL), P. aeruginosa (MIC = 100 mg/mL),
S. aureus (MIC = 200 mg/mL), E. faecalis (MIC = 100 mg/mL)
StemsMethanolic extractS. aureus (MIC = 7 mg/mL), E. coli (MIC = 6 mg/mL),
P. aeruginosa (MIC = 6 mg/mL)		[133]
FruitsMethanol extractE. coli (MIC = 400 μg/mL), Agrobacterium sp (MIC = 400 μg/mL),
Rhizobium sp (MIC = 3.2 μg/mL), B. pumilus (MIC = 320 μg/mL), B. subtilis (MIC = 340 μg/mL)		[134]
LeavesMethanolic extractB. subtilis (MIC = 12.5 μg/mL), S. aureus (MIC = 25.0 μg/mL),
E. coli (MIC = 1000 μg/mL), P. aeruginosa (MIC = 1000 μg/mL), S. Typhimurium (MIC = 1000 μg/mL)		[135]
FruitsEthanolic extractE. coli (MIC = 50 mg/mL), P. aeruginosa (MIC = 25 mg/mL),
S. aureus (MIC = 25 mg/mL), S. epidermidis (MIC = 25 mg/mL), E. faecalis (MIC = 25 mg/mL), B. subtilis (MIC = 25 mg/mL), M. luteus (MIC = 25 mg/mL)		[136]
Methanolic extractE. coli (MIC = 50 mg/mL), P. aeruginosa (MIC = 25 mg/mL),
S. aureus (MIC = 25 mg/mL), S. epidermidis (MIC = 25 mg/mL), E. faecalis (MIC = 25 mg/mL), B. subtilis (MIC = 25 mg/mL), M. luteus (MIC = 25 mg/mL), C. tropicalis (MIC = 50 mg/mL)
Aqueous extractE. coli (MIC = 100 mg/mL), P. aeruginosa (MIC = 200 mg/mL),
S. aureus (MIC = 12.5 mg/mL), S. epidermidis (MIC = 200 mg/mL), E. faecalis (MIC = 200 mg/mL), B. subtilis (MIC = 100 mg/mL), M. luteus (MIC = 100 mg/mL), C. tropicalis (MIC = 100 mg/mL)
FruitsMethanolic extractH. pylori (MIC = 128 μg/mL)[117]
Table
Table 4. The anti-oxidant activities of the Z. lotus extracts.
Table 4. The anti-oxidant activities of the Z. lotus extracts.
CountryRegionUsed PartExtractMethodResultsReferences
MoroccoNortheasternFruitsAqEDPPHIC50 = 116 ± 0.02 µg/mL[35]
β-carotene bleaching test12.5 µg/mL (42.24% of oxidation), 25 µg/mL (31.68% of oxidation), 50 µg/mL (26.92% of oxidation), and 100 µg/mL (21.11% of oxidation)
Region of Ihahen (southern region)FruitsHxEDPPHIC50 = 8 mg/mL[101]
MtOHIC50 = 5 mg/mL
DiMtnIC50 > 10 mg/mL
LeavesHxEIC50 > 40 mg/mL
MtOHIC50 = 0.7 mg/mL
DiMtnIC50 > 40 mg/mL
Fez (Zouagha-Moulay Yaâcoub)SeedsMtOHDPPHIC50 = 1.33 ± 0.01 mg/mL[18]
EtOHIC50 = 1.32 ± 0.09 mg/mL
AqEIC50 = 3.11 ± 0.05 mg/mL
Region of Sidi Sliman FruitsAqEDPPH74.87 ± 16.74 mg TE/g EDW[20]
ABTS46.31 ± 11.02 mg TE/g EDW
FRAP55.30 ± 2.30 mg AAE/g EDW
LeavesDPPH241.75 ± 17.37 mg TE/g EDW
ABTS301.34 ± 8.26 mg TE/g EDW
FRAP160.10 ± 2.30 mg AAE/g EDW
Zaouiat Cheikh Area, Oued Zem CityFruitsMtOHDPPHIC50 = 131.01 µg/mL[134]
ABTSIC50 = 52.42 µg/mL
TunisiaOudhref-Gabes Region
(South of Tunisia)		RootsPeEABTSIC50 = 14.76 ± 0.02 mg/L[25]
DiMtnABTSIC50 = 136.58 ± 0.41 mg/L
MtOHIC50 = 14.31 ± 0.13 mg/L
EtOHIC50 = 27.42 ± 0.32 mg/L
AqEIC50 = 8.96 ± 0.38 mg/L
PeEDPPHIC50 = 101.06 ± 0.40 mg/L
DiMtnIC50 = 192.33 ± 0.60 mg/L
MtOHIC50 = 18.03 ± 0.61 mg/L
EtOHIC50 = 39.50 ± 0.49 mg/L
AqEIC50 = 16.46 ± 0.60 mg/L
PeETAC105.56 ± 0.37 mg AAE/mg EDW
DiMtn91.11 ± 2.20 mg AAE/mg EDW
MtOH304.07 ± 1.11 mg AAE/mg EDW
EtOH167.41 ± 7.40 mg AAE/mg EDW
AqE191.85 ± 0.00 mg AAE/mg EDW
LeavesPeEABTSIC50 = 28.98 ± 0.06 mg/L
DiMtnIC50 = 29.51 ± 1.23 mg/L
MtOHIC50 = 23.48 ± 0.63 mg/L
EtOHIC50 = 249.37 ± 1.26 mg/L
AqEIC50 = 29.01 ± 0.44 mg/L
PeEDPPHNot active
DiMtnNot active
MtOHIC50 = 33.66 ± 0.11 mg/L
EtOHIC50 = 375.50 ± 1.50 mg/L
AqEIC50 = 64.80 ± 0.36 mg/L
PeETACNot active
DiMtn154.44 ± 6.20 mg AAE/mg EDW
MtOH142.47 ± 0.85 mg AAE/mg EDW
EtOH173.09 ± 2.99 mg AAE/mg EDW
AqE99.26 ± 4.62 mg AAE/mg EDW
FruitsMtOHABTSIC50 = 173.93 ± 0.88 mg/L
AqEIC50 = 342.25 ± 1.25 mg/L
MtOHDPPHIC50 = 343.00 ± 1.32 mg/L
AqEIC50 = 383.33 ± 0.29 mg/L
MtOHTAC26.42 ± 2.26 mg AAE/mg EDW
AqE40.74 ± 3.39 mg AAE/mg EDW
Tozeur (South of Tunisia)FruitsEtOHTAC75.981 mg GAE/g EDW[141]
DPPH0.289 mg/mL
Region Sidi Aich in the south LeavesMtOHDPPHIC50 = 1.28 ± 0.13 mg/mL[142]
FRAPIC50 = 2.18 ± 0.05 mg/mL
KairouanLeavesAqEDPPHIC50 = 0.4 µg/mL[143]
EtOHIC50 = 0.1 µg/mL
RouhiaAqEIC50 = 0.6 µg/mL
EtOHIC50 = 0.03 µg/mL
MahresAqEIC50 = 0.55 µg/mL
EtOHIC50 = 0.46 µg/mL
MahdiaAqEIC50 = 0.64 µg/mL
EtOHIC50 = 0.35 µg/mL
BengardaneLeavesMtOHTAC30.95 ± 0.01 mg GAE/g EDW[19]
DPPHIC50 = 18.27 ± 0.28 µg/mL
FruitsTAC23.87 ± 0.34 mg GAE/g EDW
DPPHIC50 = 12.16 ± 0.31µg/mL
SeedsTAC22.03 ± 3.08 mg GAE/g EDW
DPPHIC50 = 18.57 ± 6.67µg/mL
Oued EssederLeavesMtOHTAC30.91 ± 0.06 mg GAE/g EDW
DPPHIC50 = 16.60 ± 1.58 µg/mL
FruitsTAC25.02 ± 0.55 mg GAE/g EDW
DPPHIC50 = 15.15 ± 0.90 µg/mL
SeedsTAC22.80 ± 0.15 mg GAE/g EDW
DPPHIC50 = 11.41 ± 0.35 µg/mL
AlgeriaNot definedFruitsAqEDPPHIC50 = 11–30 µg/mL[114]
Steppic Region of TiaretStemsMtOHDPPH480.20 ± 40.64 mg AAE/g EDW[133]
ItalyAddaura (the northern slopes of Monte Pellegrino, Palermo, Italy)Stem barkMtOHDPPH304.02 ± 4.80 mg AAE/g EDW[140]
Metal chelating39.01 ± 4.30 mg EDTAE/g EDW
FRAP296.68 ± 1.81 mg TE/g EDW
Abbreviations: DPPH: 2-2-diphenyl-1-picrylhydrazyl; FRAP: ferric reducing/antioxidant power; TAC: total antioxidant capacity; ABTS: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); TE: Trolox equivalent; EDW: extract dry weight; AAE: ascorbic acid equivalent; GAE: gallic acid equivalent; EDTAE: ethylenediaminetetraacetic acid equivalent; IC50: median inhibitory concentration. Extracts: AqE: aqueous extract; HxE: hexane extract; MtOH: methanol extract; DiMtn: dichloromethane extract; EtOH: ethanol extract; PeE: petroleum ether extract.
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Bencheikh, N.; Radi, F.Z.; Fakchich, J.; Elbouzidi, A.; Ouahhoud, S.; Ouasti, M.; Bouhrim, M.; Ouasti, I.; Hano, C.; Elachouri, M. Ethnobotanical, Phytochemical, Toxicological, and Pharmacological Properties of Ziziphus lotus (L.) Lam.: A Comprehensive Review. Pharmaceuticals 2023, 16, 575. https://doi.org/10.3390/ph16040575

AMA Style

Bencheikh N, Radi FZ, Fakchich J, Elbouzidi A, Ouahhoud S, Ouasti M, Bouhrim M, Ouasti I, Hano C, Elachouri M. Ethnobotanical, Phytochemical, Toxicological, and Pharmacological Properties of Ziziphus lotus (L.) Lam.: A Comprehensive Review. Pharmaceuticals. 2023; 16(4):575. https://doi.org/10.3390/ph16040575

Chicago/Turabian Style

Bencheikh, Noureddine, Fatima Zahrae Radi, Jamila Fakchich, Amine Elbouzidi, Sabir Ouahhoud, Mohammed Ouasti, Mohamed Bouhrim, Imane Ouasti, Christophe Hano, and Mostafa Elachouri. 2023. "Ethnobotanical, Phytochemical, Toxicological, and Pharmacological Properties of Ziziphus lotus (L.) Lam.: A Comprehensive Review" Pharmaceuticals 16, no. 4: 575. https://doi.org/10.3390/ph16040575

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