The molecular mechanisms of anti-glycating activities of Cinnamomum cassia, Aegle marmelos, and Embillica officinalis along with some of their pure compounds are elucidated in this study. Diabetic Wistar rats were divided into five groups (n=7-10/group): i) diabetic control; ii) treated with 20 mg/kg cinnamaldehyde (TCA); iii) treated with 20 mg/kg ellagic acid (EA); iv) with 20 mg/kg eugenol (EU); and v) treated with Aminoguanidine (AG) as positive control for 42 days. At the end, 24-h urine was collected and rats were sacrificed, blood was collected for biochemical tests. Additionally the pancreas and kidneys were processed for histology and western blotting analysis. Pancreatic sections were triple stained for insulin, glucagons, and nuclei (DAPI). Kidney sections were stained for AGEs (and mainly CML). Kidney total RNA was isolated and real-time qPCR was done to check the expression levels of RAGE (receptor for advanced glycation end products) and IL-1β. The biochemical data showed that there was increased blood glucose, HbA1c, and serum AGEs levels in the untreated-diabetic group which were lowered with the treatment of TCA, EA, and EU in a varying degree. TCA decreased HbA1c upto 5% in diabetic rats. The AGEs concentration in EU and TCA treated rats was similar as non-diabetic control rats. The serum insulin was significantly increased in EA and TCA treated groups. The urinary microalbumin excretion from the kidneys was decreased by all groups, but maximum decrease was found in EU group. The immunohistochemical results of pancreatic sections showed increased β-cells in the TCA, EA, and EU groups as compared to untreated-diabetic group. The AGEs, and mainly CML, were decreased in the TCA, EA, and EU treated rat kidney sections. This immunohistochemical data were found in according to serum AGEs data, in which EU and TCA maximally decreased AGEs concentration in serum. In untreated-diabetic rats, RAGE over expression was observed which were dramatically decreased in all treatment groups. The maximum decreased in RAGE over expression was observed in TCA group. The IL-1β was also over expressed in untreated-diabetic group which were also decreased in all treatment groups. The maximum decreased in IL-1β over expression was observed in TCA group.

Molecular mechanism of anti-glycating activities of some dietary agents and their active constituents