Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of the isolated polysaccharide from Momordica charantia in diabetic rats. The polysaccharide was isolated from M. charantia (MCP) and was characterized by using FTIR and LC-MS/MS. The diabetic model was established by intraperitoneal administration of streptozotocin in male Wistar rats and grouped into control, diabetic, metformin (500 mg kg−1 day−1), and treatment (10 mg kg−1 day−1) groups. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31, and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the polysaccharide structure of the isolated fraction. High blood glucose was normalized by MCP treatment in diabetic rats. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1, and Hes1 while it scaled down the levels of Notch1, Dll4, and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining levels of hes1, cyclin d1, and VEGF proteins were increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets’ regeneration and suggest that modulation of notch and angiogenesis pathways may play a pivotal role in the restoration of the islets to relieve diabetes.

Polysaccharides extracted from Momordica charantia could normalize the level of blood glucose in STZ-induced type 2 diabetic rats through modulation of notch and angiogenesis singling pathways. Given that this effect was associated with the increased expression of Pdx-1 and Insulin in the pancreas, the isolated polysaccharide is expected to be introduced as a convenient medicine in the treatment of diabetes through modulation of β-cell regeneration.