2. Academic Validation
  3. Eurocristatine, a plant alkaloid from Eurotium cristatum, alleviates insulin resistance in db/db diabetic mice via activation of PI3K/AKT signaling pathway

Eurocristatine, a plant alkaloid from Eurotium cristatum, alleviates insulin resistance in db/db diabetic mice via activation of PI3K/AKT signaling pathway

  • Eur J Pharmacol. 2020 Nov 15;887:173557. doi: 10.1016/j.ejphar.2020.173557.
Hui Zhang 1,  Junfeng Hui 2,  Jing Yang 3,  Jianjun Deng 4,  Daidi Fan 5
Affiliations

Affiliations

  • 1 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China. Electronic address: [email protected].
  • 2 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China. Electronic address: [email protected].
  • 3 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China. Electronic address: [email protected].
  • 4 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China. Electronic address: [email protected].
  • 5 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi, 710069, China. Electronic address: [email protected].
PMID: 32946868 DOI: 10.1016/j.ejphar.2020.173557
Abstract

Eurocristatine (ECT) is an alkaloid isolated from Eurotium cristatum, and it has been used in multiple applications. However, its use as a treatment for type 2 diabetes mellitus (T2DM) has not yet been reported. In this study, we investigated the anti-T2DM effect of ECT and explored its potential molecular mechanism. In vivo, after treatment with ECT (20, 40 mg/kg) for 6 weeks, fasting blood glucose (FBG) was remarkably reduced in db/db mice. Moreover, glucose tolerance, Insulin sensitivity and hyperinsulinemia were ameliorated treatment with ECT. The values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed that ECT could alleviate liver toxicity caused by diabetes in db/db mice. In vitro, ECT (15 and 30 μM) alleviated Insulin resistance by increasing glucose consumption, glucose uptake and glycogen content in high glucose-induced HepG2 cells. The Western blotting (WB) results showed that ECT could upregulate the expression of phosphatidylinositol 3-kinase (PI3K), increase the phosphorylation of Insulin Receptor substrate 1 (IRS1) and protein kinase B (Akt) in vivo and in vitro. Besides, ECT improved the glycogen content by inhibiting the expression of glycogen synthase kinase3β (GSK3β) and promoting that of glycogen synthase (GS). Furthermore, administration of the PI3K/Akt signaling pathway inhibitor LY294002 abolished the beneficial effects of ECT. These findings are the first to verify that ECT has the potential to improve glucose metabolism and alleviate Insulin resistance by activating the PI3K/Akt signaling pathway in db/db mice.

Keywords

Eurocristatine; Glucose metabolism; Insulin resistance; PI3K/AKT pathway; Type 2 diabetes mellitus (T2DM).

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