الفهرس | Only 14 pages are availabe for public view |
Abstract “Structure modification converts the hepatotoxic tacrine into novel hepatoprotective analogs.” The liver is responsible for critical functions like metabolism, secretion, storage, detoxification, and excretion of various compounds. However, there is currently no approved drug treatment for liver fibrosis treatment. Hence, this study aimed to explore the potential hepatoprotective effect of chlorinated and non-chlorinated 4-phenyl-tetrahydroquinoline derivatives. Originally developed as tacrine analogs with reduced hepatotoxicity, these compounds not only lacked hepatotoxicity but also displayed a remarkable hepatoprotective effect. Treatment with these derivatives notably prevented chemically induced elevation of hepatic indicators associated with liver injury. Additionally, the compounds restored the activities of defense antioxidant enzymes, as well as levels of inflammatory markers (TNF-α and IL-6), apoptotic proteins (Bax and Bcl2), and fibrogenic mediators (α-SMA and TGF-β), to normal levels. Histopathologic analysis confirmed the hepatoprotective activity of tetrahydroquinolines. Furthermore, computer-assisted simulation docking results were highly consistent with the observed in vivo activities. In conclusion, the designed tacrine analogs exhibited a hepatoprotective role in acute liver damage, possibly through its antioxidative, anti-inflammatory, and antifibrotic effects. |