title: Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights.
abstract: 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.
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.|Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Ramesha H
authors.initials: RH
authors.lastname: Jayaramaiah
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Sachin B
authors.initials: SB
authors.lastname: Agawane
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Garikapati
authors.initials: G
authors.lastname: Vannuruswamy
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Arvind M
authors.initials: AM
authors.lastname: Korwar
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.|Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Anand
authors.affiliation: Krantisinh Nana Patil College of Veterinary Science, Shirwal, Satara 412 801, Maharashtra, India.
authors.forename: Vitthal S
authors.initials: VS
authors.lastname: Dhaygude
authors.affiliation: National Centre for Cell Science, Pune 411007, Maharashtra, India.
authors.forename: Mahemud L
authors.initials: ML
authors.lastname: Shaikh
authors.affiliation: Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, Maharashtra, India.
authors.forename: Rakesh S
authors.initials: RS
authors.lastname: Joshi
authors.affiliation: National Centre for Cell Science, Pune 411007, Maharashtra, India.
authors.forename: Ramanamurthy
authors.initials: R
authors.lastname: Boppana
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Mahesh J
authors.initials: MJ
authors.lastname: Kulkarni
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.|CSIR- Institute of Genomics and Integrative Biology, Mall Road, New Delhi 110007, India.
authors.forename: Hirekodathakallu V
authors.initials: HV
authors.lastname: Thulasiram
authors.affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India.
authors.forename: Ashok P
authors.initials: AP
authors.lastname: Giri
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005054:Eugenol / Q000494:pharmacology* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood*; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D008807:Mice, Inbred BALB C; D031339:Ocimum / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D040901:Proteomics
chemical_list: D001786:Blood Glucose; D005054:Eugenol; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D065089:Glycoside Hydrolase Inhibitors; D006146:Guanidines; D010936:Plant Extracts; C004479:pimagedine