Anti-hyperglycemic effect of fangchinoline isolated from Stephania tetrandra Radix in streptozotocin-diabetic mice.
Kampo medicine, Stephania tetrandra Radix (Stephania) in Boi-ogi-to increases the blood insulin level and falls the blood glucose level in streptozotocin (STZ)-diabetic ddY mice. These actions of Stephania are potentiated by Astragalus membranaceus Bunge Radix (Astragali) in Boi-ogi-to (Liu et al., J. Traditional Med., 17, 253-260, 2000). In the present study, actions of bis-benzylisoquinoline alkaloids isolated from Stephania were investigated in the hyperglycemia of STZ-diabetic mice. A main bis-benzylisoquinoline alkaloid, fangchinoline (0.3-3 mg/kg) significantly fell the blood glucose level of the diabetic mice in a dose-dependent manner. The effect of fangchinoline was 3.9-fold greater than that of water extract of Stephania. However, another main compound, tetrandrine (1-100 mg/kg) did not have any effect. The water extract of Astragali did not affect singly but potentiated the anti-hyperglycemic action of fangchinoline (0.3 mg/kg). Out of used compounds (1 mg/kg) isolated from Stephania, fangchinoline, fangchinoline 2'-N-alpha-oxide and 2'-N-norfangchinoline, which are substituted with 7-hydroxy side chain for 7-O-methyl side chain, decreased to near 50% of high blood glucose level. In addition, tetrandrine 2'-N-beta-oxide, tetrandrine 2'-N-alpha-oxide, tetrandrine 2-N-beta-oxide, fangchinoline 2'-N-alpha-oxide, which are added to 2- or 2'-N-oxide side chain, also decreased to near 50% of the high blood glucose level. In conclusion, fangchinoline but not tetrandrine from Stephania shows the anti-hyperglycemic action in the STZ-diabetic mice. The demethylation of 7-O-position and/or addition of 2- or 2'-N-oxide side chain in bis-benzylisoquinoline compounds in Stephania have a role for the induction of the anti-hyperglycemic actions.
Tsutsumi
Taiki
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa, Japan.
Kobayashi
Shinjiro
S
Liu
Yuan Ying
YY
Kontani
Hitoshi
H
D000470:Alkaloids / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D044182:Benzylisoquinolines / Q000737:chemistry / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005215:Fasting; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D031609:Stephania tetrandra / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D044182:Benzylisoquinolines; D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007328:Insulin; C009438:tetrandrine; C060802:fangchinoline