Dai Weibo, Chen Chang, Feng Huiting, Li Guangru, Peng Weiwen, Liu Xin, Yang Jing, Hu Xianjing
Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, Zhongshan, China.
Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, Zhongshan, China.
J Ethnopharmacol. 2021 Jul 15;275:114140. doi: 10.1016/j.jep.2021.114140. Epub 2021 Apr 27.
Ficus pandurata Hance (FPH) is a traditional Chinese herbal medicine, which is commonly used for liver protection in the folk of Southeast China. However, the medicinal part and pharmacological mechanism have not been clarified yet.
This study aims to investigate the medicinal part of FPH for liver protection and uncover the potential mechanism.
Acute alcoholic liver damage (ALD) mice model induced by intragastric administration with 50% alcohol was used to evaluate the liver protection of FPH. Different parts of FPH, including the root (FPHR), stem (FPHS), leaf (FPHL), and whole plant (FPHWP), were selected to investigate the liver-protected efficacy and determine which part is the medicinal part. Acute oral toxicity (AOT) test was performed to determine the acute toxicity of FPH on Kunming mice. The liver-protected effect of FPH was determined by evaluating the liver function, liver morphological changes, and liver pathological changes. The underlying mechanism was investigated by evaluating the effect on oxidative stress, inflammation, and apoptosis in liver tissues via ELISA, H&E staining, Western Blot, and TUNEL staining assays.
In the screening test for medicinal parts of FPH, all of the extracts from FPHR, FPHS, FPHL, and FPHWP could alleviate the acute ALD of mice, including reducing abnormal levels of AST, ALT, and relative liver weight. Especially, the alleviated efficacies of FPHS and FPHL were better than those of FPHWP and FPHR, showing that the aerial part (FPHAP, including the stem and leaf), is probably the medicinal part of FPH against acute ALD. In the AOT test, FPHAP at the maximum administration dosage (480 g/kg, calculated based on the quantity of crude material) did not induce obvious abnormality and death of mice, and had no significant influence on body weight, as well as the relative organ weight, showing that the maximum tolerated dose (MTD) of FPHAP was 480 g/kg on Kunming mice. In the anti-acute ALD study, FPHAP significantly reduced the levels of AST, ALT, LDH, ROS, MDA, TNF-α, IL-1β, IL-18, and IL-6, alleviated the morphology of liver injury, increased the levels of SOD and GSH, up-regulated the expressions of Nrf-2, HO-1 and NQO1, and reduced apoptosis of liver cells in acute ALD mice, indicating that FPHAP could significantly alleviate acute ALD by suppressing oxidative stress, inflammation, and apoptosis.
FPH could protect acute alcohol-induced liver damage of mice by suppressing oxidative stress, inflammation, and apoptosis. Our study provides scientific evidence for the therapeutic effect of Ficus pandurata Hance in acute ALD mice and suggests its potential development in humans for liver protection, supporting its traditional application.
琴叶榕是一种传统的中草药,在中国东南部民间常用于肝脏保护。然而,其药用部位和药理机制尚未阐明。
本研究旨在探究琴叶榕肝脏保护的药用部位,并揭示其潜在机制。
采用灌胃50%乙醇诱导的急性酒精性肝损伤(ALD)小鼠模型来评估琴叶榕的肝脏保护作用。选取琴叶榕的不同部位,包括根(FPHR)、茎(FPHS)、叶(FPHL)和全株(FPHWP),研究其肝脏保护功效并确定药用部位。进行急性经口毒性(AOT)试验以确定琴叶榕对昆明小鼠的急性毒性。通过评估肝功能、肝脏形态变化和肝脏病理变化来确定琴叶榕的肝脏保护作用。通过ELISA、苏木精-伊红(H&E)染色、蛋白质免疫印迹法(Western Blot)和末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)染色试验评估其对肝脏组织氧化应激、炎症和细胞凋亡的影响,以探究潜在机制。
在琴叶榕药用部位筛选试验中,FPHR、FPHS、FPHL和FPHWP的所有提取物均能减轻小鼠急性ALD,包括降低天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)异常水平和相对肝脏重量。特别是,FPHS和FPHL的缓解效果优于FPHWP和FPHR,表明地上部分(FPHAP,包括茎和叶)可能是琴叶榕抗急性ALD的药用部位。在AOT试验中,最大给药剂量(480 g/kg,按生药量计算)的FPHAP未引起小鼠明显异常和死亡,对体重以及相对器官重量无显著影响,表明FPHAP对昆明小鼠的最大耐受剂量(MTD)为480 g/kg。在抗急性ALD研究中,FPHAP显著降低了AST、ALT、乳酸脱氢酶(LDH)、活性氧(ROS)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)和白细胞介素-6(IL-6)水平,减轻了肝损伤形态,提高了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平,上调了核因子E2相关因子2(Nrf-2)、血红素加氧酶-1(HO-1)和醌氧化还原酶1(NQO1)的表达,并减少了急性ALD小鼠肝细胞凋亡,表明FPHAP可通过抑制氧化应激、炎症和细胞凋亡显著减轻急性ALD。
琴叶榕可通过抑制氧化应激、炎症和细胞凋亡保护小鼠急性酒精性肝损伤。我们的研究为琴叶榕对急性ALD小鼠的治疗作用提供了科学证据,并表明其在人类肝脏保护方面的潜在开发价值,支持其传统应用。