A novel insulin-releasing substance, phanoside, from the plant Gynostemma pentaphyllum.
Extracts from Gynostemma pentaphyllum Makino (Cucurbitaceae), a Southeast Asian herb, has been reported to affect numerous activities resulting in antitumor, cholesterol-lowering, immunopotentiating, antioxidant, and hypoglycemic effects. We have isolated one active compound by ethanol extraction, distribution in n-butyl alcohol/water, solid phase extraction/separation, and several rounds of reverse phase high pressure liquid chromatography. We have shown by NMR and mass spectrometry that this active compound is a novel saponin, a gypenoside, which we have named phanoside (21-,23-epoxy-,3beta-,20-,21-trihydroxydammar-24-ene-3-O-([alpha-d-rhamnopyranosyl(1-->2)]-[beta-d-glycopyranosyl(1-->3)]-beta-d-lyxopyranoside)), with a molecular mass of 914.5 Da. Phanoside is a dammarane-type saponin, and four stereoisomers differing in configurations at positions 21 and 23 were identified, each of which were found to stimulate insulin release from isolated rat pancreatic islets. We have also found that the stereoisomers are interconvertible. Dose-dependent insulin-releasing activities at 3.3 and 16.7 mM glucose levels were determined for the racemic mixture containing all four stereoisomers. Phanoside at 500 microM stimulates insulin release in vitro 10-fold at 3.3 mM glucose and potentiates the release almost 4-fold at 16.7 mM glucose. At these glucose levels, 2 microm glibenclamide stimulates insulin release only 2-fold. Interestingly, beta-cell sensitivity to phanoside is higher at 16.7 mM than at 3.3 mM glucose, although insulin responses were significantly increased by phanoside below 125 microM only at high glucose levels. Also when given orally to rats, phanoside (40 and 80 mg/ml) improved glucose tolerance and enhanced plasma insulin levels at hyperglycemia.
Norberg
Ake
A
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Hoa
Nguyen Khanh
NK
Liepinsh
Edvards
E
Van Phan
Dao
D
Thuan
Nguyen Duy
ND
Jörnvall
Hans
H
Sillard
Rannar
R
Ostenson
Claes-Göran
CG
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000188:drug therapy; D029774:Gynostemma / Q000737:chemistry*; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007536:Isomerism; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
C492975:21,23-epoxy-3,20,21-trihydroxydammar-24-ene-3-O-(rhamnopyranosyl-1-2)-(glucopyranosyl-1-3)lyxopyranoside; D007328:Insulin; D010936:Plant Extracts; D012503:Saponins; D000431:Ethanol; D005947:Glucose