Insulin secretion and cyclooxygenase enzyme inhibition by cabernet sauvignon grape skin compounds.
Bioassay-guided isolation and purification of hexane and ethyl acetate extracts of Cabernet Sauvignon grape skin yielded nine compounds (1-9), which were identified as beta-sitosterol-6'-linolenoyl-3-O-beta-D-glucopyranoside (1), beta-sitosterol (2), beta-sitosterol-3-O-beta-D-glucoside (3), oleanolic acid (4), oleanolic aldehyde (5), resveratrol (6), (+)-epsilon-viniferin (7), (-)-catechin (8), and 1-triacontanol (9). The structures of these compounds were established by spectroscopic methods. The compounds were assayed for insulin production using an INS-1 cell assay. In a dose-response study, compound 4 stimulated insulin production of INS-1 cells by 20.23, 87.97, 1.13, and 6.38 ng of insulin/mg of protein at 6.25, 12.5, 25, and 50 microg/mL, respectively. This trend was similar to the dose-dependent insulin production of INS-1 cells by glucose. Compound 5 also showed a dose-dependent insulin production in this assay. The isolated compounds were also assayed for cyclooxygenase-1 and -2 (COX) enzyme inhibitory activities. At 100 microg/mL, compounds 2, 3, and 4 inhibited the COX-2 enzyme by 11, 12, and 10%, respectively, but did not show activities on the COX-1 enzyme. Compounds 6, 7, and 8 at 100 microg/mL inhibited the COX-1 enzyme by 98, 99, and 98%, respectively, and the COX-2 enzyme by 0, 47, and 72%, respectively. This is the first report of beta-sitosterol-6'-linolenoyl-3-O-beta-D-glucopyranoside (1) from grape skin and insulin secretion activities of compounds 4 and 5.
Zhang
Yanjun
Y
Bioactive Natural Products and Phytoceuticals, Department of Horticulture, Michigan State University, East Lansing, Michigan 48824, USA.
Jayaprakasam
Bolleddula
B
Seeram
Navindra P
NP
Olson
Lawrence K
LK
DeWitt
David
D
Nair
Muraleedharan G
MG
D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008565:Membrane Proteins; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D027843:Vitis / Q000737:chemistry*
D000872:Anthocyanins; D016861:Cyclooxygenase Inhibitors; D007328:Insulin; D007527:Isoenzymes; D008565:Membrane Proteins; D009828:Oleanolic Acid; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat