TY - JOUR ID - 20603 TI - Spinosin ameliorates insulin resistance by suppressing reactive oxygen species-associated inflammation JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Ge, Chi-yu AU - Yang, Ling AU - Zhang, Jun-li AU - Wei, Zhi-feng AU - Feng, Feng AD - School of Pharmacy, Jiangsu Food and Pharmaceutical Science College, Huai’an, Jiangsu 223005, China AD - Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China Y1 - 2022 PY - 2022 VL - 25 IS - 7 SP - 850 EP - 858 KW - Inflammation KW - Insulin receptor substrate - proteins KW - insulin resistance KW - Reactive Oxygen Species KW - Spinosin KW - Zizyphus DO - 10.22038/ijbms.2022.64154.14127 N2 - Objective(s): Spinosin is the predominant C-glycoside flavonoid derived from the seeds of Zizyphus jujuba var. Spinosa (Rhamnaceae). The present study aimed to investigate the effects of spinosin on insulin resistance (IR) in vascular endothelium.Materials and Methods: The anti-IR effect of spinosin was evaluated in a high-fat diet (HFD) treated mice model. The effects of spinosin pretreatment on reactive oxygen species (ROS)-associated inflammation in Human umbilical vein endothelial cells (HUVEC) were evaluated by western blot analysis and reverse transcription-polymerase chain reaction. The effect of spinosin on insulin-mediated endothelium-dependent vasodilation of rat aortae was further evaluated. Results: Spinosin at 20 mg/kg alleviates increased mice’s body weight, fasting serum glucose, oral glucose tolerance, serum insulin, insulin resistance index, and serum lipid of HFD-treated mice. Spinosin at 20 μM suppressed ROS overproduction, and inhibited ROS-related HUVEC inflammation by inhibiting mRNA expression of tumor necrosis factor-α and interleukin-6. In addition, spinosin at 0.1 μM showed a vasodilation effect of isoprenaline-pretreated rat aortae and increased insulin-mediated NO production in endothelial cells. These effects were shown to be related to the spinosin regulating serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) facilitated/phosphoinositide 3-kinase (PI3K) signaling. Conclusion: Spinosin may ameliorate IR and ROS-associated inflammation, and increase endothelial NO production by mediating IRS-1/PI3K/endothelial nitric oxide synthase (eNOS) pathway. UR - https://ijbms.mums.ac.ir/article_20603.html L1 - https://ijbms.mums.ac.ir/article_20603_49766832a3f63b61f5e879b1a329e83b.pdf ER -