Antidiabetic activities of a cucurbitane-type triterpenoid compound from Momordica charantia in alloxan-induced diabetic mice

Momordica charantia has been used to treat a variety of diseases, including inflammation, diabetes and cancer. A cucurbitane-type triterpenoid [(19R,23E)-5β, 19-epoxy-19-methoxy-cucurbita-6,23,25-trien-3 β-o-l] previously isolated from M. charantia was demonstrated to possess significant cytotoxicity against cancer cells. The current study investigated the effects of this compound (referred to as compound K16) on diabetes using an alloxan-induced diabetic mouse model. C57BL/6J mice were intraperitoneally injected with alloxan (10 mg/kg body weight), and those with blood glucose concentration higher than 10 mM were selected for further experiments. Diabetic C57BL/6J mice induced by alloxan were administered 0.9% saline solution, metformine (10 mg/kg body weight), or K16 (25 or 50 mg/kg body weight) by gavage for 4 weeks, followed by analysis of blood glucose level, glucose tolerance, serum lipid levels and organ indexes. The results demonstrated that compound K16 significantly reduced blood glucose (31-48.6%) and blood lipids (13.5-42.8%; triglycerides and cholesterol), while improving glucose tolerance compared with diabetic mice treated with saline solution, suggesting a positive improvement in glucose and lipid metabolism following K16 treatment. Furthermore, similarly to metformine, compound K16 markedly upregulated the expression of a number of insulin signaling pathway-associated proteins, including insulin receptor, insulin receptor substrate 1, glycogen synthase kinase 3β, Akt serine/threonine kinase, and the transcript levels of glucose transporter type 4 and AMP-activated protein kinase α1. The results of the current study demonstrated that compound K16 alleviated diabetic metabolic symptoms in alloxan-induced diabetic mice, potentially by affecting genes and proteins involved in insulin metabolism signaling.