Details

Autor(en) / Beteiligte

• Lin, Guo‐Shuai
• Zhao, Mao‐Mao
• Fu, Qi‐Chao
• Zhao, Shu‐Yi
• Ba, Tao‐Tao
• Yu, Hong‐Xia

Titel

Palmatine attenuates hepatocyte injury by promoting autophagy via the AMPK/mTOR pathway after alcoholic liver disease

Ist Teil von

• Drug development research, 2022-11, Vol.83 (7), p.1613-1622

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Alcoholic liver disease is one of the diseases with the highest fatality rate worldwide. The cellular process of autophagy which recycles damaged organelles to maintain protein and organelle homeostasis is found to positively influence survival during hepatic insufficiency, although the mechanism is poorly understood. Palmatine (PLT) has a variety of biological functions, such as broad‐spectrum antibacterial action, neuroprotective, antioxidant stress, and antiviral and anti‐inflammatory activities. However, it is not known whether PLT has a protective effect against alcoholic liver injury. Here, we investigated the protective effect of PLT in a cellular model of alcohol‐induced acute liver injury and further explored its mechanism of action. In this study, we show for the first time that PLT attenuates alcohol‐induced hepatocyte injury by promoting autophagy to play an essential protective role. As PLT treatment induced a brief increase in LC3‐II conversion and p62 degradation, it also upregulated the expression of ATG5 and ATG7. The expression levels of the proapoptotic proteins Bax, Caspase 3, and Caspase 9 significantly decreased, while the antiapoptotic protein levels of Bcl‐2 upregulated after treatment with PLT. However, in presence of the autophagy inhibitor, 3‐methyladenine, the effect of PLT in inhibiting ethanol‐induced hepatocyte injury reversed significantly. Mechanistically, the protective effects of PLT may be mediated by promoting the activation of the AMP‐activated protein kinase/mammalian target of rapamycin signaling pathway. Therefore, we believe that the development of alcoholic liver injuries may be controlled by PLT by inhibiting hepatocyte apoptosis through the autophagy pathway. The study lays a solid theoretical and practical basis for future animal models and clinical studies of PLT.