College of Pharmacy, Wannan Medical College, Wuhu, Anhui, China.
Institute of Natural Daily Chemistry, Wannan Medical College, Wuhu, Anhui, China.
Pharm Biol. 2020 Dec;58(1):1277-1289. doi: 10.1080/13880209.2020.1859552.
(Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic.
To investigate hepatotoxicity and related mechanisms induced by ethanol extracts of different parts of in rats.
Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-α, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined.
The LD of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-α levels ( < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group.
ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of .
(Thunb.)Roem. et Schult.(金粟兰科)是一种广泛用作民间药物治疗炎症性疾病的草药,尽管它是有毒的。
研究不同部位的金粟兰乙醇提取物对大鼠的肝毒性及相关机制。
将 Sprague Dawley 大鼠分为对照组(Con)、根乙醇提取物(ER)、茎乙醇提取物(ES)和叶乙醇提取物(EL)组,并进行急性口服毒性研究。大鼠分别接受 4.14、3.20 和 1.16 g/kg/d 的提取物,持续 14 天。测定肝指数、肝功能和氧化应激生物标志物、肝病理、超微结构、TNF-α、ICAM-1 和 Nrf2/HO-1 蛋白表达水平。
ER、ES 和 EL 的 LD 均高于 10.35、8.05 和 2.90 g/kg/p.o。各提取物组的肝指数显著增加。EL 显著增加 TP、GLB、AST、ALT、ALP、TBA、MDA、ICAM-1 和 TNF-α水平( < 0.01),并引起最明显的病理和超微结构变化。ES 和 EL 明显降低 T-SOD、GSH、CAT 和 CHOL 水平。ES(0.77±0.06,2.33±0.20)和 EL(0.23±0.04,2.14±0.16)组的 Nrf2 和 HO-1 蛋白表达明显降低,ER 组(1.08±0.10;3.39±0.21)则略有降低。
ES 和 EL 通过氧化应激和 Nrf2/HO-1 通路引起比 ER 更强的肝毒性,而根是一种更好的药用部位,为临床研究、安全应用和合理开发提供了依据。