Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile and tissue antioxidant status in rats fed a high-cholesterol diet

The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.     

Acute and chronic toxicological studies of Ajuga iva in experimental animals

Ajuga iva (L.) Schreber (AI), is widely used in the Moroccan pharmacopoeia as a panacea (cure-all), and specifically for gastrointestinal disorders and diabetes, and as an anthelmintic. No toxicological investigations have been carried out on this plant. We have previously observed that single oral doses (2-14 g/kg) of a lyophilised aqueous extract of AI (AI-extract) in mice or daily oral administration of 10 mg/kg of AI-extract in rats for 2 weeks did not result in any adverse effects. We have now evaluated AI-extract for its behavioural and pharmaco-toxicological effects after acute and chronic administration by the oral and intraperitoneal routes in rats and mice. No toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. However, single intraperitoneal injections of the AI-extract (1500-5500 mg/kg BW) produced a dose-dependent increase in adverse effects in the general behaviour and the mortality rate; the LD50 of acute intraperitoneal dose was 3.6 g/kg. In chronic toxicological studies in rats, the AI-extract (administered orally at daily doses of 100, 300 and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver and the kidneys at the end of the study (3 months) showed normal architecture suggesting no morphological disturbances.     

Vasorelaxant effect of the aqueous extract of Ajuga iva in rat aorta

The aim of the present study was to investigate the ex vivo and in vitro vascular activity of the aqueous extract of Ajuga iva (L.) Schreber (Labiatae) in normotensive Wistar rats. Chronic oral administration of the extract of Ajuga iva did not significantly affect the systolic blood pressure. In aorta isolated from Ajuga iva-treated rats, the contractile response to noradrenaline was depressed compared to the responses obtained in aorta from untreated rats but the endothelium-dependent relaxation evoked by acetylcholine was not affected. In vitro, Ajuga iva extract inhibited the contraction evoked by noradrenaline. The addition of Ajuga iva extract during the plateau phase of noradrenaline-evoked contraction produced a relaxation that was sensitive to N-nitro-L-arginine. After pre-incubation of the artery in the presence of the plant extract, vasorelaxant effect was markedly less pronounced. The endothelium-dependent relaxation induced by acetylcholine was concentration-dependently blunted in the presence of Ajuga iva extract in the bathing solution. This study indicates that the aqueous extract of Ajuga iva possesses NO-mediated and NO-independent vasorelaxing properties in vitro while only the endothelium-independent effect was observed ex vivo.     

Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.     

Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats

The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (p<0.001). Repeated daily oral administration significantly reduced blood glucose levels after 4 days of treatment (p<0.01). In diabetic rats, a significant reduction in blood glucose levels was observed 1 h after a single oral administration (p<0.001). Repeated oral administration reduced blood glucose levels at the 4th day (p<0.001). No change in total plasma cholesterol and triglyceride levels was observed after both a single and repeated oral administration in both normal and diabetic rats. In addition, plasma insulin levels and body weight remained unchanged after 15 days of repeated oral administration in normal and diabetic rats. We conclude that Inula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.     

Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats

The antihyperglycemic effect of syringaldehyde (1), purified from the stems of Hibiscus taiwanensis, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) showing type-1 like diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 7.2 mg/kg of 1 attenuated significantly the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A glucose uptake test showed that 1 exhibits an increase of glucose uptake activity in a concentration-related manner. Moreover, an effect by 1 was shown for insulin sensitivity in STZ-diabetic rats. The compound was found to increase insulin sensitivity in STZ-diabetic rats. These results suggest that syringaldehyde (1) can increase glucose utilization and insulin sensitivity to lower plasma glucose in diabetic rats.     

Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats

Ethnopharmacological relevance

The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated.

Aim of the study

The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose and after daily dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats.

Materials and methods

After a single oral dose of CS-extract (20 mg/kg; predetermined as optimum), plasma glucose, insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal and OHH rats (hypercaloric diet and forced limited physical activity); glibenclamide (GLB; 2.5 mg/kg) was used as reference. In the sub-chronic study, the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR), atherosclerotic and cardioprotective indices were calculated.

Results

A single dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo-glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or insulin, but IR decreased significantly. The hypoglycemic effect was lower in normal rats. In the sub-chronic study in OHH rats, the test substances (CS-extract > GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR, TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while cardioprotective indices increased only by CS-extract, with no effect on BW, urea or creatinine.

Conclusion

Sub-chronic administration of CS-extract in OHH Meriones shawi rats normalized glycemia and decreased the elevated levels of insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several components of the metabolic syndrome and decreased atherosclerotic and increased cardioprotective indices, CS-extract may have cardiovascular protective effect. The present study validates the traditional use of coriander in diabetes.     

Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats

The antihyperglycemic action of puerarin, purified from the roots of Pueraria lobata, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Bolus intravenous injection of puerarin decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Similar treatment with puerarin also decreased the plasma glucose in normal rats, although the effect was not as great as that in STZ-diabetic rats. Puerarin at the effective dose (15.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, puerarin enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of puerarin in STZ-diabetic rats for 3 days. These results suggest that puerarin can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.     

Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats

The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZ-induced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration.     

Antidiabetic and antioxidant effects of oleanolic acid from Ligustrum lucidum Ait in alloxan‐induced diabetic rats

The present study evaluated the antidiabetic and antioxidant effects of oleanolic acid (OA) from Ligustrum lucidum Ait (LLA) in alloxan‐induced diabetic rats. OA in the alloxan‐induced diabetic rats showed significant hypoglycemic activity by lowering blood glucose (at doses of 60 and 100 mg/kg for 40 days). The levels of serum total cholesterol (TC), triglycerides (TG) and low‐density lipoprotein cholesterol (LDL‐c) in the OA‐treated diabetic rats were lower, and the high‐density lipoprotein cholesterol (HDL‐c) level was higher than in the control diabetic rats. A significant reduction in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels of diabetic rats following OA treatment was also observed. Furthermore, OA treatment decreased the malondialdehyde (MDA) level, but increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activities of the liver and kidney in diabetic rats. These results indicate that OA could protect the liver function avoiding alloxan‐induced damage; OA had hypoglycemic, hypolipidemic and antioxidant efficacy in the diabetic rats. The antioxidant ability of OA might be one of the mechanisms of its hypoglycemic and hypolipidemic effects. Copyright © 2009 John Wiley & Sons, Ltd.     

Hypoglycemic effect of aqueous extract of seabuckthorn (Hippophae rhamnoides L.) seed residues in streptozotocin‐induced diabetic rats

An extract of seabuckthorn (Hippophae rhamnoides L.) seed residues has been shown to possess hypoglycemic and hypolipidemic properties in normal mice. The present study investigated the effects of an aqueous extract of seabuckthorn seed residues (ASSR) on serum glucose, lipid profiles and antioxidant parameters in streptozotocin‐induced diabetic rats. Male Sprague‐Dawley rats were divided into four groups: a normal control group; diabetic control group; diabetic groups supplemented with 5 mg/kg body weight glibenclamide (reference drug) and 400 mg/kg body weight ASSR. Diabetes in rats was induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight). Vehicle (distilled water), glibenclamide and ASSR were administered orally to normal and diabetic rats once a day lasting for 4 weeks. The data showed that administration of ASSR significantly lowered the serum glucose, triglyceride and nitric oxide levels in diabetic rats. Moreover, ASSR treatment also increased serum superoxide dismutase activity and glutathione level markedly. These results show that ASSR has hypoglycemic, hypotriglyceridemic and antioxidant effects in streptozotocin‐induced diabetic rats, suggesting that ASSR supplementation can be useful in preventing diabetic complications associated with hyperlipidemia and oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.     

栝蒌根散对糖尿病模型大鼠血糖、血脂的影响

目的:探讨栝蒌根散对糖尿病大鼠血糖、血脂的影响,分析其降糖作用与剂量之间的关系。方法:SPF级雄性Wistar大鼠,给予36 mg.kg-1链脲佐菌素(STZ)ip建立2型糖尿病模型。将成模大鼠按随机表随机分为模型组、盐酸二甲双胍组、参芪降糖颗粒组和栝蒌根散低、中、高(2,4,6 g.kg-1)剂量组,每组10只,每天ig相应的药物。10只正常大鼠作为正常组,每天ig2 mL生理盐水。ig前和ig 8周后各测一次空腹血糖和体重,最后从腹主动脉采血,化验各组大鼠的甘油三脂和胆固醇。结果:栝蒌根散低、高剂量均能降低链脲佐菌素所致糖尿病大鼠血糖(P<0.01),低剂量作用最强,中剂量无效。栝蒌根散3个剂量均能降低2型糖尿病大鼠血脂(P<0.05),但不能控制大鼠体重的下降。结论:栝蒌根散能降低糖尿病模型大鼠的血糖,其作用与剂量之间不存在量效关系。其降脂作用明显,但不能改变糖尿病大鼠体重下降的趋势。     

Hypoglycemic properties of aqueous bark extract of Ceiba pentandra in streptozotocin-induced diabetic rats

The claim by Nigerian traditional herbal medicine practitioners that the silk cotton tree, Ceiba pentandra L. Gaertn (Bombacaceae) barks extract has antidiabetic properties was investigated. Diabetes mellitus was induced with streptozotocin and graded doses of the aqueous bark extract were then administered ad libitum in drinking water to the experimentally diabetic rats for 28 days. Administration of the aqueous bark extract caused a statistically significant reduction in plasma glucose level in streptozotocin induced diabetic rats. The extract appeared non-toxic as evidenced by normal serum levels of AST, ALT, ALP and bilirubin. The data appear to support the hypoglycemic effects of C. pentandra.     

Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced diabetic rats

Single and repeated oral administration of the water extracts of Spergularia purpurea (SP) at a dose of 10 mg/kg were tested on hypoglycaemic activity in normal and streptozotocin-induced diabetic rats. In normal rats, the water extract of SP decreased significantly the plasma glucose levels 4 h after single oral administration (P<0.01), and one week after repeated oral administration (P<0.05). A significant decrease of plasma glucose levels was observed 6 h after a single oral administration of the water extract of S. purpurea in severe hyperglycaemic rats (n=6) from 22.78+/-0.60 to 11.21+/-0.49 mmol/l (P<0.001). On other hand, water extract of S. purpurea normalised plasma glucose levels after two weeks of repeated oral administration in diabetic rats; 24.05+/-1.16 versus 7.18+/-0.51 mmol/l (P<0.001) at the start and 2 weeks after water extract administration, respectively. We conclude that the water extract of SP induces hypoglycaemic activity when administered orally in normal and STZ diabetic rats. In order to determine the active principle (s) responsible of the hypoglycaemic effect, preliminary phytochemical analysis of the water extract has been investigated.     

Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism

The hypoglycemic and anti-diabetic effect of Rehmannia glutinosa oligosaccharide (ROS) in glucose-induced hyperglycemic and alloxan-induced diabetic rats and its mechanism was investigated in this paper. It was found that pretreatment of ROS in normal rats with 100 mg/kg for 3 days, i.p., induced a partial prevention of hyperglycemia caused by glucose (2g/kg, i.p.), while when hyperglycemia was induced in adrenalectomized (ADX) rats, the preventive effect of ROS on hyperglycemia was lost. In alloxan-induced diabetic rats, ROS (100 mg/kg for 15 days, i.p.) showed a significant decrease in blood glucose level and hepatic glucose-6-phosphatase activity with an increase in hepatic glycogen content. Furthermore, ROS raised plasma insulin level and lowered plasma corticosterone level in alloxan-induced diabetic rats. The results indicated that oligosaccharide of Rehmannia glutinosa Libosch. exerted a significant hypoglycemic effect in normal and alloxan-induced diabetic rats. The regulatory mechanism of ROS on glucose metabolism was adrenal dependent and had a close relation with the neuroendocrine system.     

Effect of the desert plant Retama raetam on glycaemia in normal and streptozotocin-induced diabetic rats

The effect of the aqueous extract of Retama raetam (RR) on blood glucose levels was investigated in fasting normal and streptozotocin-induced diabetic rats after single and repeated oral administration. The aqueous extract of RR at a dose of 20mg/kg significantly reduced the blood glucose in normal rats 6h after a single oral administration (P<0.005) and two weeks after repeated oral administration (P<0.05). This hypoglycaemic effect is more pronounced in streptozotocin (STZ) diabetic rats (P<0.001). The aqueous extract of RR had no effect on basal plasma insulin levels indicating that the underlying mechanism of RR activity is extra-pancreatic. These findings suggest that the aqueous extract of RR possess significant hypoglycaemic effect in both normal and STZ diabetic rats.     

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.     

Hypoglycemic and hypolipidemic effects of the total triterpene acid fraction from Folium Eriobotryae

For seeking the good natural material to develop new agent to treat diabetes, the total triterpene acid (TTA) fraction extracted from Folium Eriobotryae [leaves of Eriobotrya japonica (Thunb.) Lindl.] was evaluated for its hypoglycemic and hypolipidemic potential through normal, alloxan and streptozotocin-induced diabetic mice administered with graded oral doses (100, 200, 300 mg/(kg day)) for 7 or 14 days. The results showed that a dose of 300 mg/kg of TTA is the most effective dose to cause significant (p < 0.01) hypoglycemic and/or hypolipidemic effects on normal, alloxan and streptozotocin-induced diabetic mice. This dose also significantly (p < 0.01) lowered the glycosylated serum protein (GSP), total cholesterol (TC) and triglyceride (TG) level in severely diabetic mice. Furthermore, TTA increased the superoxide dismutase activity (SOD) and the serum insulin level of diabetic mice. These evidences indicated that the total triperpene acid fraction from Folium Eriobotryae has a high anti-diabetic potential along with a good hypolipidemic profile.     

Cholesterol-lowering activity of the aqueous extract of Spergularia purpurea in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasma cholesterol concentrations 6h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma triglycerides levels increased significantly 6h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05). In diabetic rats, SP treatment caused a significant decrease of plasma cholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of triglycerides levels was observed 6h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01). On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats. We conclude that the aqueous extract of SP exhibits a cholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats.     

Hypoglycemic and hypolipidemic effects of fresh leaf aqueous extract of Cymbopogon citratus Stapf. in rats

The present study was designed to investigate the hypoglycemic and hypolipidemic effects of the single, daily oral dosing of 125-500 mg/kg of fresh leaf aqueous extract of Cymbopogon citratus Stapf. (CCi) in normal, male Wistar rats for 42 days. The average weights of rats per group were taken at 2 weeks interval for 42 days. On day 43, blood samples from the rats were collected for fasting plasma glucose (FPG), total cholesterol, triglycerides, low-density lipoproteins (LDL-c), very low-density lipoprotein (VLDL-c) and high-density lipoprotein (HDL-c) assays through cardiac puncture under halothane anesthesia. Acute oral dose toxicity study of CCi was also conducted using limit dose test of the Up and Down Procedure statistical program (AOT425StatPgm, Version 1.0) at a dose of 5000 mg/kg body weight/oral route. Our results showed CCi to lower FPG and lipid parameters dose dependently (p<0.05) while raising the plasma HDL-c level (p<0.05) in same dose-related fashion but with no effect on plasma triglycerides level (p>0.05). Results of acute oral toxicity showed CCi to be of low toxicity and as such could be considered relatively safe on acute exposure. Thus, confirming its folkloric use and safety in suspected Type 2 diabetic patients.