Hepatoprotective effect of dihydroxy piperlongumine in high cholesterol-induced non-alcoholic fatty liver disease zebrafish via antioxidant activity

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are a growing epidemic and the most common liver diseases. Consumption of a western diet with high fats alters redox status, induces inflammation, and impairs the physiological function of hepatocytes. However, the pharmacological market lacks anti-NAFLD/NASH drugs. Long pepper (Piper longum L) is used in traditional Mongolian medicine for treating hyperlipidemia. Piperlongumine (PL) is a bioactive compound of Piper longum L, which usually possesses anticancer activities due to its ROS elevation property. However, when PL was demethylated they behave as an antioxidant. Previously, we found dihydroxy piperlongumine (DHPL) possesses high antioxidant activity among the hydroxy piperlongumines, which makes us curious to reveal the anti-NAFLD effect. A high-cholesterol diet (HCD) was chosen to induce NAFLD zebrafish model, and the antioxidant and lipid-lowering effects of DHPL were evaluated. Histological alterations of NAFLD were also scored along with gene expression to explore the molecular mechanism. DHPL reduced lipid accumulation in both short-term and long-term feeding trials. DHPL increases antioxidant activity and lipid-lowering gene expression and decreases hepatic triglyceride, oxidative stress, and lipogenic genes. In conclusion, DHPL halted the progression of HCD-induced NAFLD in the zebrafish model.

Automated summary

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common liver diseases caused by a western diet high in fats, which induce inflammation and impair hepatocyte function. Currently, there is a lack of pharmacological drugs for treating NAFLD/NASH. However, long pepper contains a bioactive compound called Piperlongumine (PL) that has potential antioxidant properties. In this study, demethylated dihydroxy piperlongumine (DHPL) was shown to have high antioxidant activity and was effective in reducing lipid accumulation and gene expression associated with NAFLD in a zebrafish model. DHPL may have therapeutic potential for halting the progression of NAFLD.