title: Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi.
abstract: Rheum emodi is used as a culinary plant across the world and finds an eminent role in the Ayurvedic and traditional Chinese systems of medicine. The plant is known to principally contain 1,8-dihydroxyanthraquinones (DHAQs) like rhein, aloe emodin, emodin, chrysophanol and physcion that possess diverse pharmacological and therapeutic actions. The present work deals with developing a platform technology for isolation of these DHAQs and evaluating their anti-diabetic potential. Herein, we report the anti-hyperglycemic activity and alpha glucosidase (AG) inhibitory actions of five isolated DHAQs from R. emodi. All the five isolated DHAQs showed good anti-hyperglycemic activity with aloe emodin exhibiting maximum lowering of blood glucose in an oral glucose tolerance test. However, on evaluation of the AG inhibitory potential of the DHAQs only emodin exhibited potent intestinal AG inhibition (93 ± 2.16%) with an IC50 notably lower than acarbose. Subsequent kinetic studies indicated a mixed type of inhibition for emodin. In vivo studies using oral maltose load showed almost total inhibition for emodin when compared to acarbose. Molecular docking studies revealed the presence of an allosteric topographically distinct 'quinone binding site' and showed that interaction with Ser 74 occurs exclusively with emodin, which is vital for AG inhibition. The net benefit from the glucose lowering effect and mixed type inhibition by emodin would enable the administration of a small dosage that is safe and non-toxic in the case of prolonged use in treating diabetes.
authors.affiliation: Medicinal Natural Products Research Laboratory, Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Mumbai, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Arvindekar
authors.forename: Tanaji
authors.initials: T
authors.lastname: More
authors.forename: Pavan V
authors.initials: PV
authors.lastname: Payghan
authors.forename: Kirti
authors.initials: K
authors.lastname: Laddha
authors.forename: Nanda
authors.initials: N
authors.lastname: Ghoshal
authors.forename: Akalpita
authors.initials: A
authors.lastname: Arvindekar
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage* / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D012250:Rheum / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D000520:alpha-Glucosidases; C004315:danthron