The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.     

Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties

Ziziphus nummularia, a small bush of the Rhamnaceae family, has been widely used in traditional folk medicine, is rich in bioactive molecules, and has many reported pharmacological and therapeutic properties. Objective: To gather the current knowledge related to the medicinal characteristics of Z. nummularia. Specifically, its phytochemical contents and pharmacological activities in the treatment of various diseases such as cancer, diabetes, and cardiovascular diseases, are discussed. Methods: Major scientific literature databases, including PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, Henriette’s Herbal Homepage, Dr. Duke’s Phytochemical and Ethnobotanical Databases, were searched to retrieve articles related to the review subject. General web searches using Google and Google scholar were also utilized. The search period covered articles published between 1980 and the end of October 2021.The search used the keywords ‘Ziziphus nummularia’, AND (‘phytochemical content’, ‘pharmacological properties, or activities, or effects, or roles’, ‘anti-inflammatory’, ‘anti-drought’, ‘anti-thermal’, ‘anthelmintic’, ‘antidiabetic’,’ anticancer’, ‘anticholinesterase’, ‘antimicrobial’, ‘sedative’, ‘antipyretic’, ‘analgesic’, or ‘gastrointestinal’). Results: This plant is rich in characteristic alkaloids, especially cyclopeptide alkaloids such as nummularine-M. Other phytochemicals, including flavonoids, saponins, glycosides, tannins, and phenolic compounds, are also present. These phytochemicals are responsible for the reported pharmacological properties of Z. nummularia, including anti-inflammatory, antioxidant, antimicrobial, anthelmintic, antidiabetic, anticancer, analgesic, and gastrointestinal activities. In addition, Z. nummularia has anti-drought and anti-thermal characteristics. Conclusion: Research into the phytochemical and pharmacological properties of Z. nummularia has demonstrated that this plant is a rich source of novel bioactive compounds. So far, Z. nummularia has shown a varied pharmacological profile (antioxidant, anticancer, anti-inflammatory, and cardioprotective), warranting further research to uncover the therapeutic potential of the bioactives of this plant. Taken together, Z. nummularia may represent a new potential target for the discovery of new drug leads.     

Chemical Constltuents from the Roots of Zizyphus jujuba Mill. var. spinosa (I)

The chemical constituents of the roots of Zizyphus jujuba Mill. var. spinosa were investigated with a combination of Sephadex LH-20 column, centrifugal partition chromatography and RP-18 low pressure liquid chromatography. We isolated seven flavonoids-quercetin ( 1 ), (+)-dihydroquercetin ( 2 ), (+)-dihydrokaempferol ( 7 ), quercetin-3-0-β-glucoside ( 8 ), 2-hydroxynaringenin ( 11 ), rutin ( 12 ), and quercetin 3-0-(2^G-β-D-xylopyranosylrutinoside) ( 13 ); four catechins-(-)-gallocatechin ( 3 ), (-)-epigallocatechin ( 4 ), (-)-catechin ( 5 ), and (-)-epicatechin ( 6 ); and two phenolic carboxylic acids-p-hydroxybenzoic acid ( 9 ) and protocatechuic acid ( 10 ) from the water soluble fraction of the ethanolic extract NMR date of 13 were assigned by 2D NMR techniques.     

Studies on Chemical Constituent of Zizyphus Jujuba in Hebei China

Introduction Jujuba is the fruit of Zizyphus genus(Rhamnaceae) which has been used as a crude drug. Now quite a lot of botanists, chemists and pharmacologists at home and abroad have been deeply interested in the studies on it. Besides the studies on its fruit, a great deal of research work on its other parts has been done So far more     

Isolation of a new triterpene derivative and in vitro and in vivo anticancer activity of ethanolic extract from root bark of Zizyphus nummularia Aubrev

The various parts of Zizyphus nummularia has been used traditionally in several disease conditions. However, its anticancer activity and mechanism of action remain to be elucidated. Considering this, the objective of this study was to isolate, identify and screen for possible anticancer activity in vitro and in vivo of the ethanolic extract (EE) and isolated identified compound (IC) from Z. nummularia root bark. The in vitro activity against human breast cancer, leukaemia, ovarian cancer, colon adenocarcinoma and human kidney carcinoma cell lines was determined. The in vivo activity in female Swiss albino mice against Ehrlich ascites carcinoma (EAC) was determined. The isolated compound is a new triterpene derivative. EE/IC showed cytotoxicity against different cell lines. The administration of EE/IC decreased tumour parameters such as tumour volume, viable tumour cell count and increased body weight, haematological parameters and life span in comparison to the EAC control mice.     

Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg⁻¹ of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg⁻¹ of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg⁻¹ of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC₅₀) = 4.23 ± 0.18 µg mL⁻¹ of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL⁻¹ of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.     

分光光度法测定壶瓶枣中的总黄酮

建立壶瓶枣总黄酮含量的测定方法.用70％的乙醇提取总黄酮,以芦丁为对照品,在510nm处测定.平均加标回收率为98.41％,RSD为0.74％,总黄酮的含量为0.264％.该方法准确可靠,可以作为壶瓶枣总黄酮含量测定的检测方法.     

Molecular Regulation of Betulinic Acid on α3β4 Nicotinic Acetylcholine Receptors

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor’s ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative.     

微波辅助提取壶瓶枣多糖及其抗氧化性

采用微波辅助法提取了壶瓶枣多糖,并对壶瓶枣粗多糖(CP)、脱蛋白多糖(DP)对·OH、O-2·和DPPH·3种自由基的清除作用进行了研究.结果表明:壶瓶枣CP和DP对3种自由基都有明显的清除作用,清除率与多糖浓度存在明显的量效关系.壶瓶枣CP和DP对·OH、O-2·和DPPH·的半清除率(IC50)值分别为0.2312、0.9326、0.1830mg/mL和0.5049、0.2016、0.0694mg/mL.CP清除能力为DPPH·＞· OH＞O-2·,DP清除能力为DPPH· ＞O-2·＞·OH.     

Isolation,Structure Elucidation and Antimicrobial Evaluation of Natural Pentacyclic Triterpenoids and Phytochemical Investigation of Different Fractions of Ziziphus spina-christi (L.) Stem Bark Using LCHRMS Analysis

Ziziphus spina-christi L. (ZSC-L) is a tree with thorny branches, belongs to the family Rhamnaceae and grows in the sub-tropics. The purpose of this research is to isolate and partially purify bioactive components from the crude ethanol extract of the stem bark of ZSC-L. Besides, bioassay-guided fractionation of ZSC-L stem bark was conducted using different solvents. The solvents were reutilized to minimize the production cost and environmental harm. In addition, the antimicrobial activities of the fractions were analyzed, followed by metabolic profiling using LC-HRMS. The n-butanol fraction showed the highest antimicrobial efficacy, so it was subjected to further purification. For the first time, two major compounds were isolated from the stem bark of ZSC-L and identified as lupane-type pentacyclic triterpenoids betulinic acid and betulin. Both compounds were used as antibacterial and anticancer agents and considered as a green product as the extraction procedure reduced the use of hazardous chemicals. Metabolic characterization of ZSC-L and its bioactive fractions were performed using LC-HR-ESI-MS and the results revealed the dereplication of 36 compounds belonging to different chemical classes. Flavonoids and triterpenes were the most prominent metabolite classes in the different fractions. The molecular docking results were obtained by studying the interaction of betulin and betulinic acid with antimicrobial receptors (4UYM, 1IYL, 1AJ2, 6J7L, 1AD4, 2VEG) to support the in vitro results. Our study highlights that Ziziphus spina-christi and its phytoconstituents, especially triterpenoids, act as a promising antimicrobial candidate in pharmaceutical and clinical applications.