1,2,3,4,6 Penta-O-galloyl-β-d-glucose, a bioactivity guided isolated compound from Mangifera indica inhibits 11β-HSD-1 and ameliorates high fat diet-induced diabetes in C57BL/6 mice.
Methanolic leaf extract of Mangifera indica (MEMI) was subjected to bioactivity guided fractionation in order to identify the active antidiabetic constituent. 32 fractions were evaluated for possible 11β-HSD-1 inhibition activity under in vitro conditions. The EA-7/8-9/10-4 fraction was evolved as a most potent fraction among all the fractions and it was identified as well known gallotannin compound 1,2,3,4,6 penta-O-galloyl-β-d-glucose (PGG) by spectral analysis. Based on these results the PGG was further evaluated in ex vivo 11β-HSD-1 inhibition assay and high fat diet (HFD)-induced diabetes in male C57BL/6 mice. Single dose (10, 25, 50 and 100mg/kg) of PGG and carbenoxolone (CBX) have dose dependently inhibited the 11β-HSD-1 activity in liver and adipose tissue. Furthermore, HFD appraisal to male C57BL/6 mice caused severe hyperglycemia, hypertriglyceridemia, elevated levels of plasma corticosterone and insulin, increased liver and white adipose mass with increase in body weight was observed compare to normal control. Also, oral glucose tolerance was significantly impaired compare to normal control. Interestingly, post-treatment with PGG for 21 days had alleviated the HFD-induced biochemical alterations and improved oral glucose tolerance compare to HFD-control. In conclusion, the PGG isolated from MEMI inhibits 11β-HSD-1 activity and ameliorates HFD-induced diabetes in male C57BL/6 mice.
Department of Pharmacognosy, Government College of Pharmacy, Bangalore, India. mohangcp@gmail.com
C G
CG
Mohan
G L
GL
Viswanatha
G
G
Savinay
C E
CE
Rajendra
Praveen D
PD
Halemani
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D052436:Adipose Tissue, White / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002229:Carbenoxolone / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005951:Glucose Tolerance Test; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D031022:Mangifera / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D018515:Plant Leaves / Q000737:chemistry
D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D007004:Hypoglycemic Agents; D007328:Insulin; C435084:pentagalloylglucose; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002229:Carbenoxolone; D003345:Corticosterone