Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

• Published in: Scientific reports Vol. 6; no. 1; p. 18798
• Main Authors: Singh, Priyanka, Jayaramaiah, Ramesha H., Agawane, Sachin B., Vannuruswamy, Garikapati, Korwar, Arvind M., Anand, Atul, Dhaygude, Vitthal S., Shaikh, Mahemud L., Joshi, Rakesh S., Boppana, Ramanamurthy, Kulkarni, Mahesh J., Thulasiram, Hirekodathakallu V., Giri, Ashok P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.01.2016; Nature Publishing Group
• Subjects: 101/58; 101/6; 13; 631/154/309/2144; 64/60; 692/308/153; 82; Advanced glycosylation end products; Animals; Blood Glucose; Bovine serum albumin; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - drug therapy; Drug Evaluation, Preclinical; Eugenol; Eugenol - pharmacology; Eugenol - therapeutic use; Glucose; Glycated Hemoglobin A - metabolism; Glycation End Products, Advanced - blood; Glycoside Hydrolase Inhibitors - pharmacology; Glycoside Hydrolase Inhibitors - therapeutic use; Guanidines - pharmacology; Hemoglobin; Humanities and Social Sciences; Insulin; Lysine; Male; Mass spectroscopy; Metabolites; Mice, Inbred BALB C; multidisciplinary; Ocimum; Ocimum - chemistry; Ocimum gratissimum; Ocimum kilimandscharicum; Ocimum tenuiflorum; Plant Extracts - pharmacology; Protein structure; Proteomics; Science; Secondary structure; Western blotting; α-Glucosidase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18798

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O . kilimandscharicum , O . tenuiflorum , O . gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro . Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.