Psoralen Suppresses Lipid Deposition by Alleviating Insulin Resistance and Promoting Autophagy in Oleate-Induced L02 Cells

Abstract

Non-alcoholic fatty liver disease (NAFLD) held a high global prevalence in recent decades. Hepatic lipid deposition is the major characteristic of NAFLD. We aim to explore the mechanisms of psoralen on lipid deposition in NAFLD. The effects of psoralen on insulin resistance, lipid deposition, the expression and membrane translocation of glucose transporter type 4 (GLUT4), autophagy, and lipogenesis enzymes were determined on sodium oleate-induced L02 cells. Chloroquine and 3-MA were employed. The AMP-activated protein kinase alpha (AMPKα) was knocked down by siRNA. Psoralen alleviated insulin resistance in sodium oleate-induced L02 hepatocytes by upregulating the expression and membrane translocation of GLUT4. Psoralen inhibited lipid accumulation by decreasing the expression of key lipogenesis enzymes. Psoralen promotes autophagy and the autophagic flux to enhance lipolysis. Psoralen promoted the fusion of the autophagosome with the lysosome. Both chloroquine and 3-MA blocked the effects of psoralen on autophagy and lipid accumulation. The AMPKα deficiency attenuated the effects of psoralen on autophagy and lipid accumulation. Our study demonstrated that as an antioxidant, psoralen attenuates NAFLD by alleviating insulin resistance and promoting autophagy via AMPK, suggesting psoralen to be a promising candidate for NAFLD.

The Coumarin-Derivative Esculetin Protects against Lipotoxicity in Primary Rat Hepatocytes via Attenuating JNK-Mediated Oxidative Stress and Attenuates Free Fatty Acid-Induced Lipid Accumulation

“…Phosphorylation of AMPK, in particular the catalytic α subunit, has been shown to decrease lipid droplet formation and to alleviate hepatic steatosis in both diet-induced MAFLD models as well as in hepatocytes treated with FAs [80][81][82]. Previous studies have revealed that coumarin derivatives act as lipidlowering agents by activating AMPK-regulated lipogenic signaling pathways or AMPKmediated autophagy [83,84]. Esculetin decreases lipogenesis and lipid uptake in FA-treated hepatocytes by phosphorylating AMPKα at Thr172 and downregulating the expression of the target gene Acc [36,53].…”

Exploring quality evaluation markers of Fructus Psoraleae based on chemometric analysis integrated with network pharmacology

“…Owing to the multiple origins of FP where the soil condition, climate, and processing methods vary from one to another, major differences were witnessed in the quality of FP, 13 posing a challenge to fully monitor and accurately evaluate its overall quality. Active ingredients in FP are coumarins, flavonoids, and phenolic compounds including psoralen, 14 isopsoralen, 15 bakuchiol, 16 psoralidin, 17 bavachinin, 18 and so forth. Nevertheless, only the total amount of psoralen and isopsoralen were stipulated in the Chinese Pharmacopoeia (ChP) for the quality standard of FP, which inevitably contradicts the multi‐component and multi‐target characteristics of TCM.…”