Puerarin Attenuates Insulin Resistance by Inhibiting Endoplasmic Reticulum Stress and Suppresses Inflammation by Modulating the JNK and IKKβ/NF-κB Pathways in Epididymal White Adipose Tissue of Mice on a High-Fat Diet

ScopeObesity is associated with insulin resistance (IR), which is characterized by endoplasmic reticulum (ER) stress in multiple organs. ER stress in adipose tissue causes metabolic disturbances and activates inflammatory signaling pathways. Puerarin, an isoflavone extracted from Pueraria lobata, exhibits antioxidant, anti-inflammatory, and antidiabetic effects. This study explores the potential mechanisms underlying puerarin's role in mitigating insulin resistance in high-fat diet (HFD)-induced obese mice.Methods and resultsIn this study, insulin resistant in mice is induced by a high-fat diet, followed by treatment with puerarin. The results demonstrate that puerarin effectively attenuates insulin resistance, including weight loss, improvement of glucose tolerance and insulin sensitivity, and activation of insulin signaling pathway. Additionally, puerarin administration suppresses ER stress by down-regulation of ATF6, ATF4, CHOP, GRP78 expressions in epididymal white adipose tissue (eWAT), along with decreased phosphorylation IRE1 alpha, PERK, and eIF2 alpha. Furthermore, puerarin exerts anti-inflammatory effects by inhibiting JNK and IKK beta/NF-kappa B pathways, leading to reduction of TNF-alpha and IL-6.ConclusionThese findings suggest that puerarin mitigates insulin resistance by inhibiting ER stress and suppressing inflammation through the JNK and IKK beta/NF-kappa B pathways. This highlights the promising clinical application of puerarin in the treatment of insulin resistance. Pueraria lobata has been used for treating diabetes in traditional Chinese medicine. Puerarin is the main bioactive component of P. lobata. The pharmacological effects of puerarin in mice fed with HFD are based on improving insulin resistance by reducing ER stress and inflammatory factors in adipose tissue. Therefore, puerarin holds promise as a potent anti-insulin resistance drug. image