A molecular connection of Pterocarpus marsupium, Eugenia jambolana and Gymnema sylvestre with dipeptidyl peptidase-4 in the treatment of diabetes.
BACKGROUND
Pterocarpus marsupium (PM) (Leguminosae), Eugenia jambolana (EJ) (Myrtaceae) and Gymnema sylvestre (GS) (Asclepiadaceae) are the most important medicinal plants in the Indian system of traditional medicine for the treatment of hyperglycemia.


OBJECTIVE
Dipeptidyl peptidase-4 (DPP-4) inhibitors are the emerging class of anti-diabetic agents. However, only few compounds are commercially available. Therefore, in the present study we tried to explore the naturally occurring PM, EJ and GS semi-standardized extracts for their potential DPP-4 inhibition in vitro and in vivo.


METHODS
DPP-4 inhibition was evaluated by in vitro inhibitory assay, and enzyme kinetics were calculated using one-phase exponential decay equation. Glucose load (2 g/kg) was administered to control and diabetic rats 30 min following extract administration (100, 200 and 400 mg/kg) orally once, and blood samples were withdrawn at 0, 0.5, 1, 1.5, 2 and 3 h to measure plasma active glucagon-like peptide-1 (GLP-1) levels.


RESULTS
PM and EJ inhibit DPP-4 potently with IC50 values of 273.73 ± 2.96 and 278.94 ± 6.73 µg/mL, respectively, compared to GS (773.22 ± 9.21 µg/mL). PM, EJ and GS exhibit long duration of action with enzyme inhibitory half-lives of 462.3, 317.2 and 153.8 min, respectively. Extracts significantly increase GLP-1 levels compared to negative control groups and peak GLP-1 level was observed at 2 h for PM and EJ, whereas for GS it was at 1.5 h


CONCLUSIONS
Taken together, results suggest the extracts may have potent DPP-4 inhibitory action, and their hypoglycemic action attributed through an increase in plasma active GLP-1 levels.
Department of Pharmacognosy .
Jayasankar
J
Kosaraju
Anil
A
Dubala
Santhivardhan
S
Chinni
Rizwan Basha
RB
Khatwal
M N
MN
Satish Kumar
Duraiswamy
D
Basavan
D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D031104:Gymnema sylvestre / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007194:India; D020128:Inhibitory Concentration 50; D008297:Male; D008515:Medicine, Ayurvedic; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D035721:Pterocarpus / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D027842:Syzygium / Q000737:chemistry*; D013997:Time Factors
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D052216:Glucagon-Like Peptide 1