Ramar Mohan Kumar, Chidambaram Kumarappan, Chandrasekaran Balakumar, Kandasamy Ruckmani
Laboratory of Pulmonary Research, National Facility for Drug Development (NFDD) for Academia, Pharmaceutical and Allied Industries, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, 620024, Tamil Nadu, India; Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational REsearch (CENTRE), Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, 620024, Tamil Nadu, India.
Department of Pharmacology & Toxicology, School of Pharmacy, King Khalid University, Abha, 68589, Saudi Arabia.
Regul Toxicol Pharmacol. 2022 Jun;131:105144. doi: 10.1016/j.yrtph.2022.105144. Epub 2022 Feb 24.
Ziziphus mauritana Lam leaves were used to treat asthma, diabetes, pain, and inflammation in the Indian traditional system of medicine. The leaves of the Ziziphus mauritiana Lam were consumed as a vegetable in Indonesia and India. The present study aims to predict the pharmacokinetic properties of flavonoids identified & quantified through U(H)PLC and to evaluate the safety of methanol extract of Ziziphus mauritana Lam leaves (MEZ) in rats. A U(H)PLC-ESI-QTOF-MS/MS was performed to identify flavonoids present in MEZ and quantified using U(H)PLC method. The in-silico ADME properties of the flavonoids were analyzed using Schrodinger Maestro software. The acute oral toxicity study was performed by administering a single dose of MEZ (5000 mg/kg) in female rats and observed for 14 days. The sub-chronic studies were carried out by oral administration of MEZ at 500, 750, and 1000 mg/kg daily for 90 days. The changes in hematological parameters, clinical biochemistry, and histopathology were observed after the treatment period. Eight flavonoids rutin, kaempferol, luteolin, myricetin, catechin, and apigenin were identified from were identified in UPLC-QTOF-MS/MS analysis. These results showed the highest amount of luteolin (5.41 μg/ml) and kaempferol (4.02 μg/ml) present in MEZ. No signs of toxicity or mortality were observed in acute toxicity studies. In the sub-chronic studies, data showed that MEZ does not produce any changes in hematological and clinical biochemical parameters compared to control rats. MEZ (1000 mg/kg) significantly (p < 0.05) reduced total cholesterol, triglycerides, in male rats, which was more prominent on day 90. The histopathological analysis also revealed no changes in the vital organs. These results conclude that MEZ was considered safe and well-tolerated in rats.
在印度传统医学体系中，毛叶枣叶被用于治疗哮喘、糖尿病、疼痛和炎症。在印度尼西亚和印度，毛叶枣叶被当作蔬菜食用。本研究旨在预测通过超高效液相色谱法（U(H)PLC）鉴定和定量的黄酮类化合物的药代动力学特性，并评估毛叶枣叶甲醇提取物（MEZ）在大鼠体内的安全性。采用超高效液相色谱-电喷雾电离-四极杆飞行时间串联质谱（U(H)PLC-ESI-QTOF-MS/MS）对MEZ中的黄酮类化合物进行鉴定，并用超高效液相色谱法进行定量。使用薛定谔大师软件分析黄酮类化合物的计算机模拟吸收、分布、代谢和排泄（ADME）特性。通过给雌性大鼠单次灌胃MEZ（5000毫克/千克）进行急性经口毒性研究，并观察14天。亚慢性研究通过每天经口给予MEZ 500、750和1000毫克/千克，持续90天。在治疗期结束后观察血液学参数、临床生化指标和组织病理学的变化。在超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF-MS/MS）分析中鉴定出8种黄酮类化合物，即芦丁、山奈酚、木犀草素、杨梅素、儿茶素和芹菜素。这些结果表明MEZ中木犀草素含量最高（5.41微克/毫升），山奈酚含量为（4.02微克/毫升）。在急性毒性研究中未观察到毒性或死亡迹象。在亚慢性研究中，数据显示与对照大鼠相比，MEZ不会引起血液学和临床生化参数的任何变化。MEZ（1000毫克/千克）显著（p<0.05）降低了雄性大鼠的总胆固醇和甘油三酯，在第90天时更为明显。组织病理学分析也显示重要器官无变化。这些结果得出结论，MEZ在大鼠中被认为是安全且耐受性良好的。
