Shahmohammadi Alireza, Mirahmadi Seyed-Mohamad-Sadegh, Rousta Ali-Mohammad, Baluchnejadmojarad Tourandokht, Roghani Mehrdad
School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar;398(3):2815-2822. doi: 10.1007/s00210-024-03448-2. Epub 2024 Sep 16.
Carbon tetrachloride (CCl4)-provoked acute liver injury (ALI) is typified by intensified apoptotic, inflammatory, and oxidative changes besides mitochondrial dysfunction. Sinomenine is an active constituent in the medicinal plant Sinomenium acutum. The main objective of this study was to determine sinomenine-induced hepatoprotection following CCl4 challenge with an emphasis on unraveling the contribution of mitochondrial biogenesis-related factors. To induce ALI, CCl4 was injected i.p. and sinomenine was orally administered at 10, 25, and 50 mg/kg. Serum factors in relation to liver dysfunction were measured in addition to hepatic analysis of apoptotic, mitochondrial biogenesis, oxidative, and inflammatory parameters. Sinomenine pretreatment significantly lowered ALT and AST, MDA, IL-6, apoptosis intensity, and TNF-α and restored mitochondrial biogenesis besides enhancement of SOD, sirtuin-1, and AMPK. Sinomenine also conferred hepatoprotective impact, as was apparent by lower pathologic changes. These effects were accompanied by changes in gene expression for AMPK/sirtuin-1/PGC-1α/PPARγ. The current study showed sinomenine hepatoprotective impact in CCl4-induced ALI that is associated with its regulation of mitochondrial biogenesis and parallel enhancement of AMPK/sirtuin-1.
四氯化碳（CCl4）诱发的急性肝损伤（ALI）的特征是除了线粒体功能障碍外，还伴有凋亡、炎症和氧化应激的加剧。青藤碱是药用植物青风藤中的一种活性成分。本研究的主要目的是确定青藤碱在CCl4攻击后对肝脏的保护作用，重点是阐明线粒体生物发生相关因子的作用。为诱导ALI，腹腔注射CCl4，并以10、25和50mg/kg的剂量口服给予青藤碱。除了对凋亡、线粒体生物发生、氧化和炎症参数进行肝脏分析外，还测量了与肝功能障碍相关的血清因子。青藤碱预处理显著降低了ALT、AST、MDA、IL-6、凋亡强度和TNF-α，并恢复了线粒体生物发生，同时增强了SOD、沉默调节蛋白-1和AMPK。青藤碱还具有肝脏保护作用，病理变化减轻即可明显看出。这些作用伴随着AMPK/沉默调节蛋白-1/PGC-1α/PPARγ基因表达的变化。本研究表明，青藤碱对CCl4诱导的ALI具有肝脏保护作用，这与其对线粒体生物发生的调节以及AMPK/沉默调节蛋白-1的平行增强有关。
