Yeast and mammalian alpha-glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi Wall.ex Meisson.
The methanolic extract of rhizome of Himalayan rhubarb Rheum emodi displayed mild yeast as well as mammalian intestinal alpha-glucosidase inhibitory activity. However, further fractionation of active extract led to the isolation of several potent molecules in excellent yields, displaying varying degrees of inhibition on two test models of alpha-glucosidase. Rhapontigenin, desoxyrhapontigenin, chrysophanol-8-O-beta-d-glucopyranoside, torachrysone-8-O-beta-d-glucopyranoside displayed potent yeast alpha-glucosidase inhibition. However chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside displayed potent to moderate mammalian alpha-glucosidase inhibitory activity. Other compounds displayed mild activity on both the tests. Except desoxyrhapontigenin and rhapontigenin that increased Vmax, other compounds including crude extract decreased the Vmax significantly (p<0.02) in yeast alpha-glucosidase test. Further kinetic analysis on mammalian alpha-glucosidase inhibition showed that chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin and torachrysone-8-O-beta-d-glucopyranoside may be classified as mixed-noncompetitive inhibitors. However, desoxyrhapontigenin and rhapontigenin may be classified as modulators of enzyme activity. Presence and position of glycoside moiety in compounds appear important for better inhibition of mammalian alpha-glucosidase. This is the first report assigning particularly, mammalian intestinal alpha-glucosidase inhibitory activity to these compounds. Chrysophanol-8-O-beta-d-glucopyranoside, desoxyrhaponticin, desoxyrhapontigenin and rhapontigenin have been isolated in substantial yields from R. emodi for the first time. Therefore, these compounds may have value in the treatment and prevention of hyperglycemia associated diabetes mellitus.
Suresh Babu
K
K
Natural Products Laboratory, Division of Organic chemistry-1, Indian Institute of Chemical Technology, Hyderabad 500007, India.
Tiwari
Ashok K
AK
Srinivas
Pullela V
PV
Ali
Amtul Z
AZ
China Raju
B
B
Rao
J Madhusudana
JM
D000818:Animals; D001667:Binding, Competitive; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D006943:Hyperglycemia / Q000188:drug therapy / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012250:Rheum / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D015003:Yeasts; D000520:alpha-Glucosidases / Q000302:isolation & purification / Q000378:metabolism
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010936:Plant Extracts; D013267:Stilbenes; D000520:alpha-Glucosidases