Institute for Genome Engineered Animal Models of Human Diseases, College of Integrative Medicine, National Center of Genetically Engineered Animal Models for International Research, Liaoning Province Key Lab of Genetically Engineered Animal Models, Dalian Medical University, Dalian, 116044, China.
Shandong Provincial Hospital, School of Laboratory Animal & Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250021, China.
Mol Nutr Food Res. 2024 Aug;68(16):e2400003. doi: 10.1002/mnfr.202400003. Epub 2024 Jul 28.
Obesity 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.
In 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 IRE1α, PERK, and eIF2α. Furthermore, puerarin exerts anti-inflammatory effects by inhibiting JNK and IKKβ/NF-κB pathways, leading to reduction of TNF-α and IL-6.
These findings suggest that puerarin mitigates insulin resistance by inhibiting ER stress and suppressing inflammation through the JNK and IKKβ/NF-κB pathways. This highlights the promising clinical application of puerarin in the treatment of insulin resistance.
肥胖与胰岛素抵抗（IR）有关，其特征是多个器官的内质网（ER）应激。脂肪组织中的 ER 应激会导致代谢紊乱，并激活炎症信号通路。葛根素是从野葛中提取的异黄酮，具有抗氧化、抗炎和抗糖尿病作用。本研究探讨了葛根素减轻高脂肪饮食（HFD）诱导肥胖小鼠胰岛素抵抗的潜在机制。
在本研究中，通过高脂肪饮食诱导小鼠胰岛素抵抗，然后用葛根素进行治疗。结果表明，葛根素能有效减轻胰岛素抵抗，包括体重减轻、改善葡萄糖耐量和胰岛素敏感性以及激活胰岛素信号通路。此外，葛根素通过下调附睾白色脂肪组织（eWAT）中 ATF6、ATF4、CHOP 和 GRP78 的表达，抑制 ER 应激，同时降低磷酸化 IRE1α、PERK 和 eIF2α。此外，葛根素通过抑制 JNK 和 IKKβ/NF-κB 通路发挥抗炎作用，导致 TNF-α 和 IL-6 减少。
这些发现表明，葛根素通过抑制 ER 应激和抑制 JNK 和 IKKβ/NF-κB 通路的炎症来减轻胰岛素抵抗。这突出了葛根素在治疗胰岛素抵抗方面有很好的临床应用前景。
