Hypoglycemic effect of quassinoids from Brucea javanica (L.) Merr (Simaroubaceae) seeds.
BACKGROUND
The seeds of Brucea javanica (L.) Merr (Simaroubaceae) are recommended by traditional practitioners for the treatment of diabetes mellitus.


OBJECTIVE
To identify the compounds responsible for blood glucose lowering effect and evaluate the acute toxicity of the compounds.


METHODS
Extracts, fractions and subfractions were administered to normoglycemic mice and the blood glucose concentration was monitored for 8 h. Bioactive compounds isolated through column chromatography were administered to normoglycemic mice and streptozotocin (STZ) rats with monitoring of blood glucose concentration at 0-8h. The acute toxicity was evaluated in mice.


RESULTS
Bioactivity-guided fractionation led to the isolation of bruceines E (1) and D (2). Normoglycemic mice administered with 1 mg/kg of 1 and 2 exhibited significant blood glucose concentration reduction of 40.07+/-11.45% and 48.82+/-13.34%, respectively. STZ induced diabetic rats administered with 1 and 2 exhibited significant blood glucose concentration reduction of 73.57+/-13.64% and 87.99+/-2.91%, respectively.


CONCLUSIONS
The reduction of blood glucose concentration by both bruceines was comparable to glibenclamide and they might act as an insulin secretagogue. The presence of a hydroxyl moiety at C(2) in 1 reduced the toxic effect by 9-fold compared to 2.
NoorShahida
Ajmi
A
MedChem Herbal Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia.
Wong
Tin Wui
TW
Choo
Chee Yan
CY
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D032269:Brucea / Q000737:chemistry*; D000440:Butanols / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008296:Malaysia; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D036702:Quassins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D001786:Blood Glucose; D000440:Butanols; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D036702:Quassins; D012997:Solvents; C030412:bruceine D; C030413:bruceine E