Da Fang-Fang, Meng Yao-Ting, Chen Yu-Feng, Yuan Zi-Wan, Liu Ying, Dai Zhong-Hua
School of Chinese Ethnic Medicine, Guizhou Minzu University, Guiyang 550025, China; Key Laboratory of Guizhou Ethnic Medicine Resource Development and Utilization in Guizhou Minzu University, State Ethnic Affairs Commission, Guiyang 550025, China.
School of Chinese Ethnic Medicine, Guizhou Minzu University, Guiyang 550025, China; Key Laboratory of Guizhou Ethnic Medicine Resource Development and Utilization in Guizhou Minzu University, State Ethnic Affairs Commission, Guiyang 550025, China.
Tissue Cell. 2025 Oct;96:102913. doi: 10.1016/j.tice.2025.102913. Epub 2025 Apr 28.
Alcoholic liver disease is regarded as a leading reason for liver cirrhosis. This study aimed to investigate the protective effect of tetracera asiatica flavonoids (TAF) on alcoholic liver injury (ALI) and explore the associated mechanisms. An ALI rat model was established and then divided into four groups, including ALI group, low-dose TAF (l-TAF) group, medium-dose TAF (m-TAF) group, and high-dose TAF (h-TAF) group. Levels of ALT, AST, ALB, SOD, MDA, NO, CAT, TG, TNF-α, IL-1β, Nrf2, Keap1, HO-1, NQO-1, and GSH-Px were measured in ALI rats in different groups. Pathological changes and inflammatory infiltration were examined using HE staining. Western blot was used to detect expressions of Nrf2, MAPK p38, PERK, NF-κB, ERK1/2 and anti-JNK1/2/3. The results showed that TAF protected against alcoholic liver injury in ALI rats by decreasing ALT and AST levels and inhibiting inflammatory response. TAF significantly reversed alcohol-induced increase in NO (P < 0.05), and remarkably decreased levels of TNF-α (P < 0.001) and IL-1β (P < 0.01), compared with the ALI group. TAF significantly increased the transcription of Nrf2, Keap1, HO-1, NQO-1 and GSH-Px gene (all P < 0.05) and inhibited the alcohol-induced upregulation of MAPK p38 expression (P < 0.001), p-NF-κB/NF-κB ratio (P < 0.001), p-ERK/1/2/ERK1/2 ratio (P < 0.05), and p-JNK1/2/3/JNK1/2/2 ratio (P < 0.05), compared with the ALI group (all P < 0.001). TAF obviously reversed effects of ALI modeling, and remarkably downregulated the expression of PERK and upregulated Nrf2 (all P < 0.001) compared with the ALI rats. In conclusion, TAF attenuates alcohol-induced livery injury through suppressing Keap-1/Nrf2/HO-1, NF-κB/MAPK and PERK/Nrf2 signaling pathways mediated oxidative stress and inflammation in ALI rats.
酒精性肝病被认为是肝硬化的主要原因。本研究旨在探讨锡叶藤黄酮（TAF）对酒精性肝损伤（ALI）的保护作用，并探索其相关机制。建立ALI大鼠模型，然后分为四组，包括ALI组、低剂量TAF（l-TAF）组、中剂量TAF（m-TAF）组和高剂量TAF（h-TAF）组。检测不同组ALI大鼠的ALT、AST、ALB、SOD、MDA、NO、CAT、TG、TNF-α、IL-1β、Nrf2、Keap1、HO-1、NQO-1和GSH-Px水平。采用HE染色检查病理变化和炎症浸润情况。用蛋白质免疫印迹法检测Nrf2、MAPK p38、PERK、NF-κB、ERK1/2和抗JNK1/2/3的表达。结果表明，TAF通过降低ALT和AST水平及抑制炎症反应，对ALI大鼠的酒精性肝损伤起到保护作用。与ALI组相比，TAF显著逆转了酒精诱导的NO升高（P<0.05），并显著降低了TNF-α（P<0.001）和IL-1β（P<0.01）的水平。与ALI组相比（均P<0.001），TAF显著增加了Nrf2、Keap1、HO-1、NQO-1和GSH-Px基因的转录（均P<0.05），并抑制了酒精诱导的MAPK p38表达上调（P<0.001）、p-NF-κB/NF-κB比值上调（P<0.001）、p-ERK/1/2/ERK1/2比值上调（P<0.05）以及p-JNK1/2/3/JNK1/2/2比值上调（P<0.05）。与ALI大鼠相比，TAF明显逆转了ALI建模的影响，并显著下调了PERK的表达，上调了Nrf2（均P<0.001）。总之，TAF通过抑制Keap-1/Nrf2/HO-1、NF-κB/MAPK和PERK/Nrf2信号通路介导的氧化应激和炎症反应，减轻酒精诱导的肝损伤。
