Njinga N S, Kola-Mustapha A T, Quadri A L, Atolani O, Ayanniyi R O, Buhari M O, Amusa T O, Ajani E O, Folaranmi O O, Bakare-Odunola M T, Kambizi L, Oladiji A T, Ebong P
African Centre for Herbal Research Ilorin (ACHRI), Central Research Laboratories, University of Ilorin, Ilorin, Nigeria.
Department of Pharmaceutical and Medicinal Chemistry, University of Ilorin, Ilorin, Nigeria.
Heliyon. 2020 Sep 21;6(9):e04853. doi: 10.1016/j.heliyon.2020.e04853. eCollection 2020 Sep.
Food and herbal usage of (HS) is attaining improved global relevance and acceptance without recourse to its potential toxic effects. This study investigated the safety profile of acute, sub-acute, sub-chronic administrations and diuretic potential of aqueous extract of calyces (AEHSC).
Acute oral toxicity, sub-acute and sub-chronic toxicity as well as diuretic studies were carried out on HS. A total of 20 Wistar rats were used for each toxicity study and assigned into four groups of five rats. The extract was administered as a single daily dose of 125, 250 and 500 mg/kg body weight (bwt) for 28 and 90 days respectively. To evaluate diuretic activity, 25 rats were divided into five groups of five rats and administered normal saline, hydrochlorothiazide 10 mg/kg, AEHSC 67.5, 125 and 250 mg/kg via the oral route. Urine sample was collected after 18 h, volume measured and concentration of electrolytes analyzed. The hematological and biochemical parameters were evaluated as well as the histopathology of kidney and liver.
The acute oral toxicity was found to be >2000 mg/kg. AEHSC did not alter concentration of WBC, MCV, MCHC, lymphocyte as well as total and direct bilirubin in the sub-acute study. However, AEHSC significantly (p < 0.05) increased total protein, albumin, globulin, Na, Cl, HCO and platelet levels, while levels of uric acid, creatinine, K, RBC, Hb, total cholesterol, triglycerides, LDL-C, HDL-C and atherogenic index were decreased significantly (p < 0.05). In the sub-chronic study, AEHSC significantly (p < 0.05) increased the levels of globulin, urea, creatinine, MCH and atherogenic index. The concentrations of uric acid, WBC, platelets and HDL-C were significantly (p < 0.05) decreased. In both the sub-acute and sub-chronic studies, activities of ALP, ALT, AST, GGT and LDH in selected organs were altered without significant increase (P < 0.05) in activity of these enzymes in the serum. The AEHSC at all the doses showed remarkable diuretic activity during 18 h period comparable to hydrochlorothiazide. The extract also showed a non-dose-dependent increase in excretion of electrolytes. Histological analysis of sections of the liver and kidney for both sub-acute and sub-chronic studies showed normal histology comparable to the control group.
This study revealed AEHSC has some toxic effects in rats on sub-chronic administration. In addition, the extracts produced a significant diuretic activity. Hence, prolonged oral consumption of the extract may not be recommended.
葫芦茶（HS）的食品和草药用途在全球范围内的相关性和接受度日益提高，但其潜在毒性作用却未得到重视。本研究调查了葫芦茶萼片水提取物（AEHSC）急性、亚急性、亚慢性给药的安全性概况及其利尿潜力。
对HS进行急性口服毒性、亚急性和亚慢性毒性以及利尿研究。每项毒性研究共使用20只Wistar大鼠，分为四组，每组五只大鼠。提取物分别以125、250和500mg/kg体重的单日剂量给药，持续28天和90天。为评估利尿活性，将25只大鼠分为五组，每组五只大鼠，通过口服途径分别给予生理盐水、10mg/kg氢氯噻嗪、67.5、125和250mg/kg的AEHSC。18小时后收集尿液样本，测量尿量并分析电解质浓度。评估血液学和生化参数以及肾脏和肝脏的组织病理学。
发现急性口服毒性>2000mg/kg。在亚急性研究中，AEHSC未改变白细胞、平均红细胞体积、平均红细胞血红蛋白浓度、淋巴细胞以及总胆红素和直接胆红素的浓度。然而，AEHSC显著（p<0.05）提高了总蛋白、白蛋白、球蛋白、钠、氯、碳酸氢根和血小板水平，而尿酸、肌酐、钾、红细胞、血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和动脉粥样硬化指数水平显著降低（p<0.05）。在亚慢性研究中，AEHSC显著（p<0.05）提高了球蛋白、尿素、肌酐、平均红细胞血红蛋白含量和动脉粥样硬化指数水平。尿酸、白细胞、血小板和高密度脂蛋白胆固醇浓度显著（p<0.05）降低。在亚急性和亚慢性研究中，所选器官中碱性磷酸酶、谷丙转氨酶、谷草转氨酶、γ-谷氨酰转移酶和乳酸脱氢酶的活性均发生改变，但血清中这些酶的活性未显著升高（P<0.05）。所有剂量的AEHSC在18小时内均显示出与氢氯噻嗪相当的显著利尿活性。提取物还显示出电解质排泄的非剂量依赖性增加。亚急性和亚慢性研究中肝脏和肾脏切片的组织学分析显示，组织学与对照组相当正常。
本研究表明，AEHSC在大鼠亚慢性给药时有一些毒性作用。此外，提取物产生了显著的利尿活性。因此，不建议长期口服该提取物。
