Phlorizin from Lithocarpus litseifolius Hance Chun ameliorates FFA-induced insulin resistance by regulating AMPK/PI3K/AKT signaling pathway

• Published in: Phytomedicine (Stuttgart) 2024-07, Vol.130, p.155743
• Main Authors: Zhao, Heng, Zhai, Bo-Wen, Zhang, Mao-Yu, Huang, Han, Zhu, Han-Lin, Yang, Han, Ni, Hai-Yan, Fu, Yu-Jie
• Format: Article
• Language: English
• ISSN: 1618-095X; 1618-095X
• DOI: 10.1016/j.phymed.2024.155743

Insulin resistance (IR) is the central pathophysiological feature in the pathogenesis of metabolic syndrome, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia. As the main active ingredient in Lithocarpus litseifolius [Hance] Chun, previous studies have shown that phlorizin (PHZ) can reduce insulin resistance in the liver. However, the effect of phlorizin on attenuating hepatic insulin resistance has not been fully investigated, and whether this effect is related to AMPK remains unclear.BACKGROUNDInsulin resistance (IR) is the central pathophysiological feature in the pathogenesis of metabolic syndrome, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia. As the main active ingredient in Lithocarpus litseifolius [Hance] Chun, previous studies have shown that phlorizin (PHZ) can reduce insulin resistance in the liver. However, the effect of phlorizin on attenuating hepatic insulin resistance has not been fully investigated, and whether this effect is related to AMPK remains unclear.The present study aimed to further investigate the effect of phlorizin on attenuating insulin resistance and the potential action mechanism.PURPOSEThe present study aimed to further investigate the effect of phlorizin on attenuating insulin resistance and the potential action mechanism.Free fatty acids (FFA) were used to induce insulin resistance in HepG2 cells. The effects of phlorizin and FFA on cell viability were detected by MTT analysis. Glucose consumption, glycogen synthesis, intracellular malondialdehyde (MDA), superoxide dismutase (SOD), total cholesterol (TC), and triglyceride (TG) contents were quantified after phlorizin treatment. Glucose uptake and reactive oxygen species (ROS) levels in HepG2 cells were assayed by flow cytometry. Potential targets and signaling pathways for attenuating insulin resistance by phlorizin were predicted by network pharmacological analysis. Moreover, the expression levels of proteins related to the AMPK/PI3K/AKT signaling pathway were detected by western blot.METHODSFree fatty acids (FFA) were used to induce insulin resistance in HepG2 cells. The effects of phlorizin and FFA on cell viability were detected by MTT analysis. Glucose consumption, glycogen synthesis, intracellular malondialdehyde (MDA), superoxide dismutase (SOD), total cholesterol (TC), and triglyceride (TG) contents were quantified after phlorizin treatment. Glucose uptake and reactive oxygen species (ROS) levels in HepG2 cells we