Jia Ziming, Zheng Yanhua, Fu Shaohua, Qu Jingjing, Tian Jie, Qu Wen, Mei Zhinan
Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Center for Disease Control and Prevention, Wuhan 430079, China.
College of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.
Evid Based Complement Alternat Med. 2022 Aug 16;2022:2011876. doi: 10.1155/2022/2011876. eCollection 2022.
Shi-Wei-Gan-Ning-San (SWGNS) is a classic Tibetan prescription, which has obvious clinical effects in the treatment of viral hepatitis, fatty liver, liver fibrosis, liver cirrhosis, liver cancer, and other liver injuries. However, animal studies and mechanism studies are still lacking. This study aimed to investigate its hepatoprotective efficacy and pharmacological mechanism in animal experiments.
Chronic liver injury was induced by oral administration of carbon tetrachloride (CCl) in Wistar rats for 13 weeks. SWGNS was administered orally to rats at doses of 235, 705, and 1410 mg/kg for 13 weeks. Blood samples were collected for biochemical, ELISA, and radioimmunoassay. Livers were harvested for H&E and immunohistochemical staining. The major constituents of SWGNS were analyzed by HPLC. In vitro experiments were used to explore the protective effect of Crocin on BRL-3A in the environment of HO.
SWGNS reversed weight loss is induced by CCl. Serum assays showed that SWGNS reduced CCl-induced alanine aminotransferase, aspartate aminotransferase, total bilirubin, and -glutamyltransferase levels and increased the total protein and albumin levels. Histopathological evaluation showed that SWGNS alleviated hepatic steatosis, fibrosis, and inflammation. Furthermore, SWNGS reduced CCl-induced elevations of TGF-1, hyaluronic acid, laminin, and collagen IV in serum and reduced the high expression of -SMA in tissues. Moreover, Crocin I and II are the main components of SWGNS. Crocin attenuated the damaging effects of HO on BRL-3A.
In conclusion, SWGNS alleviated CCl-induced chronic liver injury by inhibiting the TGF-1 pathway. This plays an important role in promoting traditional Tibetan medicine in clinical practice.
十味肝宁散是一种经典藏药方剂，在治疗病毒性肝炎、脂肪肝、肝纤维化、肝硬化、肝癌等肝脏损伤方面具有显著临床疗效。然而，目前仍缺乏动物实验及作用机制研究。本研究旨在通过动物实验探讨其保肝疗效及药理机制。
采用Wistar大鼠口服四氯化碳（CCl）13周诱导慢性肝损伤。将十味肝宁散以235、705和1410mg/kg的剂量口服给予大鼠，持续13周。采集血样进行生化、酶联免疫吸附测定（ELISA）和放射免疫分析。摘取肝脏进行苏木精-伊红（H&E）染色和免疫组织化学染色。采用高效液相色谱法（HPLC）分析十味肝宁散的主要成分。通过体外实验探讨西红花苷在过氧化氢（HO）环境下对BRL-3A细胞的保护作用。
十味肝宁散可逆转CCl诱导的体重减轻。血清检测显示，十味肝宁散降低了CCl诱导的丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素和γ-谷氨酰转移酶水平，并提高了总蛋白和白蛋白水平。组织病理学评估表明，十味肝宁散减轻了肝脂肪变性、纤维化和炎症。此外，十味肝宁散降低了CCl诱导的血清中转化生长因子-β1（TGF-β1）、透明质酸、层粘连蛋白和IV型胶原水平，并降低了组织中α-平滑肌肌动蛋白（α-SMA）的高表达。而且，西红花苷I和II是十味肝宁散的主要成分。西红花苷减轻了HO对BRL-3A细胞的损伤作用。
综上所述十味肝宁散通过抑制TGF-β1信号通路减轻CCl诱导的慢性肝损伤。这对促进藏药在临床实践中的应用具有重要意义。
