β-patchoulene protects against non-alcoholic steatohepatitis via interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation in rats
Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. β-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin , has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of β-PAE against high-fat diet-induced NASH in rats. The results displayed that β-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but β-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, β-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.
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