The anti-insulin resistance effect of scutellarin may be related to antioxidant stress and AMPKα activation in diabetic mice. Issue 4 (July 2020)

• Record Type: Journal Article
• Authors: Gao, Lingyun; Tang, Heng; Zeng, Qingfu; Tang, Ting; Chen, Ming; Pu, Peng
• Is Part Of: Obesity research & clinical practice. Volume 14:Issue 4(2020)
• Page Start: 368
• Page End: 374
• Publication Date: 2020-07
• Subjects: Scutellarein -- Insulin resistance -- Oxidative stress -- AMPK; Obesity -- Research -- Periodicals; Obesity -- Treatment -- Periodicals; Obesity -- Periodicals; Obésité -- Recherche -- Périodiques; Obésité -- Traitement -- Périodiques; Obesity -- Research; Obesity -- Treatment; Electronic journals; Periodicals; 616.398
• DOI: 10.1016/j.orcp.2020.06.005
• Languages: English
• ISSNs: 1871-403X

Abstract

Highlights: Scutellarein has a novel pharmacological effect: anti-insulin resistance. Anti-oxidant stress may be one of the important mechanisms of Sc in improving IR. TThe underlying mechanisms might be related to the activation of insulin signaling pathway and AMPKα. Our results advance the understanding of the pharmacological actions of scutellarein. Our results provide a role for scutellarein in effective management of diabetes mellitus. Abstract: Aims: Scutellarein (Sc), a natural compound and an active ingredient of Erigeronbrevis-capus (Vant.), shows anti-obesity, anti-inflammation and lipid-lowering properties in our previous study. However, no previous in vivo and vitro has been conducted to assess the effects of Sc in insulin resistance (IR). This study investigated the effects of Sc on IR and oxidative stress and explored the underlying mechanisms of action in vivo and vitro . Material and method: A well-established mouse model of IR, induced by high-fat diet (HFD) feeding, was applied in this study. The effects of Sc were evaluated on obesity, glycometabolism disorder and oxidative stress. The anti-IR effect was assessed using blood glucose, serum insulin, HOMA index, intraperitoneal glucose tolerance tests (IPGTT), intraperitoneal insulin tolerance tests (IPITT), and glucose-regulating enzyme activity. The insulin signaling pathways and AMPKα expressions were tested by Western blot. The primary culture of hepatocytes was prepared and used for confirming the above signaling pathways. Results: Obesity, IR and oxidative stress developed in HFD mice. Administration of Sc at a dose of 50 mg/kg for 16 weeks effectively attenuated these changes. Further studies revealed the antagonistic effect of Sc on IR was a result of the activation of the insulin signaling pathway and AMPKα. The primary hepatocyte test, stimulated by high glucose, further confirmed that SC exerts anti-IR through the above signaling pathway and key protein. Conclusion: These results suggested that Sc possesses not only an important novel anti-IR effect but also an anti-oxidative stress effect. These favorable effects were causally associated with weight loss and the improved glycometabolism. The underlying mechanisms might associated with the activation of the insulin signaling pathway and AMPKα. Our study promotes the understanding of the pharmacological actions of Sc, and plays a role for Sc in the effective treatment of diabetes mellitus.