Antidiabetic activity and toxicity of Zizyphus spina-christi leaves.
The effect of the butanol extract of Zizyphus spina-christi (L.), Willd (Rhamnaceae) leaves and its major saponin glycoside, christinin-A, on the serum glucose and insulin levels was studied in non-diabetic control, type-I (insulin-dependent) and type-II (non-insulin-dependent) diabetic rats. Pretreatment either with 100 mg/kg butanol extract or christinin-A potentiated glucose-induced insulin release in non-diabetic control rats. In type-II but not in type-I diabetic rats pretreatment with the butanol extract or christinin-A improved the oral glucose tolerance and potentiated glucose-induced insulin release. Treatment either with 100 mg/kg butanol extract or christinin-A reduced the serum glucose level and increased the serum insulin level of non-diabetic control and type-II diabetic rats but not of type-I diabetic rats. Effects of the butanol extract and christinin-A were similar. Pretreatment of non-diabetic control and type-II diabetic rats either with 100 mg/kg butanol extract or christinin-A enhanced the glucose lowering and insulinotropic effects of 5 g/kg glibenclamide. The hyperglycemic and hypoinsulinemic effects of 30 mg/kg diazoxide in non-diabetic control and type-II diabetic rats were inhibited and antagonized, respectively by pretreatment with the butanol extract or christinin-A. The relaxant effects of different concentrations of diazoxide on the isolated norepinephrine-contracted aortic strips were inhibited by 100 micromol/l christinin-A or 10 micromol/l glibenclamide. The combination of glibenclamide and christinin-A led to complete inhibition of the relaxant effects of different concentrations of diazoxide. At a dose level much higher than that required to produce satisfactory insulinotropic and hypoglycemic effects, the butanol extract of Zizyphus spina-christi leaves produced a depressant effect on the central nervous system in rats. Treatment of rats with 100mg/kg butanol extract for 3 months produced no functional or structural disturbances in liver and kidney and no haematological changes. In addition, the oral LD50 of the butanol extract in mice was 3820 mg/kg, while that of glibenclamide was 3160 mg/kg. Thus, Zizyphusspina-christi leaves appears to be a safe alternative to lower blood glucose. The safe insulinotropic and subsequent hypoglycemic effects of Zizyphus spina-christi leaves may be due to a sulfonylurea-like activity.
Abdel-Zaher
Ahmed O
AO
Department of Pharmacology, Faculty of Medicine, Assiut University, Egypt. ahmedosmanaz@hotmail.com
Salim
Safa Y
SY
Assaf
Mahmoud H
MH
Abdel-Hady
Randa H
RH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D031957:Ziziphus
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D013311:Streptozocin; D005905:Glyburide