Quantitative proteomics reveals Polygonum perfoliatum L. ameliorates hepatic steatosis by promoting PPARs/CPT1A/CPT2-mediated fatty acid β-oxidation

Front Pharmacol. 2023 Mar 23:14:1016129. doi: 10.3389/fphar.2023.1016129. eCollection 2023.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to end-stage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD.

Keywords: fatty acid β oxidation; hepatic steatosis; lipid metabolism; polygonum perfoliatum L.; quantitative proteomics.

Grants and funding

National Natural Science Foundation of China, Grant/Award Number: 82070633, 82100616, 82100669, 8210141127; Shanghai City Youth Science and Technology Star Project, Grant/Award Number: 21YF1434700; Program of Shanghai Academic/Technology Research Leader, Grant/Award Number: 20XD1403700.