Prevention of advanced glycation end-products formation in diabetic rats through beta-cell modulation by Aegle marmelos

BACKGROUND: Although the anti-diabetic activity of Aegle marmelos (AM) is known, however, its anti-glycation activity is not reported yet. In this study, we have investigated its anti-glycation activity under in vitro and in vivo conditions and determined possible mechanism(s) in streptozotocin-induced diabetic rats. METHODS: Effective dose of AM (400 mg/kg) was administrated orally to diabetic rats for 42 days. Thereafter, blood glucose, serum insulin, HbA1c, antioxidant status, and advanced glycation end-products (AGEs) were measured. AGEs and its receptor (RAGE) in kidney were analyzed by immunohistochemistry and immunoblotting. Additionally, pancreatic sections were co-stained for insulin and glucagon and images were acquired using NIKON TE2000E fluorescence microscopy. RESULTS: Oral administration of AM extract resulted in a significant increase in serum insulin by better functioning of β-cell and preserving pancreatic β-cell integrity in diabetic rats. Treatment of AM extract significantly (p = 0.000) prevented the formation of HbA1c in the diabetic rats (8.20 ± 0.18% vs. 11.92 ± 0.59%). The circulatory AGEs level found in diabetic rat was significantly (p = 0.002) attenuated by AM treatment (0.66 ± 0.05 mg/ml vs. 1.18 ± 0.19 mg/ml). AM treatment also reduced AGEs accumulation around Bowman’s capsule and in tubular basement membrane around arteries in diabetic rat kidney. The accumulation of RAGE was very similar to that of AGEs in diabetic rats and RAGE accumulation was also prevented by AM treatment. The extract showed potent antioxidant activity both under in vitro and in vivo systems. Eugenol, one of the active constituent of AM fruit extract, showed acute blood glucose-lowering activity in diabetic rats and enhanced glucose-stimulated insulin secretion from mice islets. CONCLUSION: AM extract prevents AGEs formation by modulating β-cell function, and eugenol may play important role in preventing complications of diabetes in this rat model.