Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

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Abstract

BACKGROUND: While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. METHODS: In alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-kappaB) activation induced by IL-1beta and IFN-gamma was investigated. RESULTS: In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-kappaB activation. CONCLUSION: We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-kappaB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

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Zhang, Z., Jiang, J., Yu, P., Zeng, X., Larrick, J. W., & Wang, Y. (2009). Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment. Journal of Translational Medicine, 7. https://doi.org/10.1186/1479-5876-7-62

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