Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Crude extract from Euphorbia prostrata extended curative period of glibenclemide in alloxan-induced diabetic rats.

OBJECTIVES: Euphorbia prostrata is traditionally used alongside antidiabetic agents to manage diabetes. Bioactive ingredients of medicinal herbs may alter the overall pharmacokinetics of antidiabetic agents. METHODS: We assessed hypoglycemic activities of ethanolic plant extract (EPE) singly and its effects on antidiabetic properties of gliclazide, glibenclemide and metformin in allaxonized rats. Varying concentrations of EPE (250 and 500 mg/kg) with or without metformin (10 mg/kg), glibenclemide (2 mg/kg) and gliclazide (5 mg/kg) were orally administered to evaluate herb-drug interaction. RESULTS: The levels of blood glucose declined significantly after treatment with metformin, glibenclemide and gliclazide singly (p<0.01) or concomitantly with EPE (p<0.001). Concentration dependent mild to moderate reduction (5.2 and 10.0%) was registered in blood glucose for 250 and 500 mg/kg of EPE respectively. The overall reduction in blood glucose due to combined treatment with EPE and standard agents was additive. On the other hand, synergistic herb-drug interaction was registered for insulin levels in rats that received glibenclamide and gliclazide alongside EPE. Extract with metformin had antagonistic insulin outcome. Regarding the duration of hypoglycemic activities, periodical changes were similar in case of glibenclamide and gliclazide separately or in combination with EPE. However, in case of metformin with extract, the blood glucose continued to decline for 14 h and retained at 15.0% below the baseline values even after 24 h of treatment. CONCLUSIONS: In conclusion, the extract itself had weak hypoglycemic effects but prolonged the therapeutic duration of metformin to more than 24 h when administered combinedly.

Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide.

BACKGROUND: Diabetes mellitus poses serious threat to the global population due to the alarming diabetic complications it leads to. The current therapeutic options available can be improved for better efficiency and maximum benefits. Combination therapy has been commonly used to improve the efficacy and to minimize the side effects of drugs in current clinical use. PURPOSE: The present study aims to assess the interaction between a natural molecule mangiferin with the commercially available oral hypoglycemic drugs metformin and gliclazide in diabetic rats. METHODS: In this study, the in vitro cytotoxicity and glucose uptake studies were performed in HepG2 cells. Based on experimental data, the combination index of the hypoglycemic drugs like metformin and gliclazide in combination with different doses of mangiferin was determined using COMPUSYN software. Further, in vivo studies were performed in HFD + STZ induced diabetic male Sprague Dawley rats. Serum parameters, enzyme markers, hepatic oxidative stress markers, gene and protein expression studies and histopathological analyses were performed in rat liver to identify the mode of action of the combination drug administration. RESULTS: The in vitro studies on HepG2 cells suggest a positive interaction of mangiferin with both metformin and gliclazide at specific concentrations as evidenced by glucose uptake. The hepatic enzymes, oxidative stress markers, carbohydrate metabolizing enzymes, gene (AMPK, Akt, ACC ß and Glut-2) and protein (PPARα, PPARγ) expression confirmed the results of the in vitro studies. Both the combinations of mangiferin with metformin and mangiferin with gliclazide exhibited potent antidiabetic effect. The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway). CONCLUSION: The overall results suggest that combination of mangiferin with both metformin and gliclazide alleviates diabetic conditions potentially at specific doses and modulates the adverse effect of high dose of commonly used OHD's. This combination therapy can be translated for its clinical use as a diabetes management strategy.

Updates on Managing Type 2 Diabetes Mellitus with Natural Products: Towards Antidiabetic Drug Development.

Over the years, natural products have shown success as antidiabetics in in vitro, in vivo studies and clinical trials. Because natural product-derived drugs are more affordable and effective with fewer side-effects compared to conventional therapies, pharmaceutical research is increasingly leaning towards the discovery of new antidiabetic drugs from natural products targeting pathways or components associated with type 2 diabetes mellitus (T2DM) pathophysiology. However, the drug discovery process is very lengthy and costly with significant challenges. Therefore, various techniques are currently being developed for the preclinical research phase of drug discovery with the aim of drug development with less time and efforts from natural products. In this review, we have provided an update on natural products including fruits, vegetables, spices, nuts, beverages and mushrooms with potential antidiabetic activities from in vivo, in vitro and clinical studies. Synergistic interactions between natural products and antidiabetic drugs, and potential antidiabetic active compounds from natural products are also documented to pave the way for combination treatment and new drug discovery, respectively. Additionally, a brief idea of the drug discovery process along with the challenges that arise during drug development from natural products and the methods to conquer those challenges are discussed to create a more convenient future drug discovery process.

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms.

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- ß (TGF-ß), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.

Effect of a New Antioxidant Enoxifol on Platelet Aggregation and Blood Rheological Properties in Rats with Experimental Diabetes Mellitus.

Effect of a new antioxidant enoxifol exhibiting antiplatelet activity in vitro and in vivo on hemostasis parameters was assessed in laboratory rats with experimental diabetes mellitus. Gliclazide, a hypoglycemic agent with antiplatelet properties, and pentoxifylline, a preparation improving blood rheology, were used as the reference drugs. Enoxifol produced a pronounced inhibitory effect on platelet aggregation in rats with experimental diabetes comparable to the effect of gliclazide and decreased blood viscosity thus demonstrating a significant effect comparable to that of pentoxifylline. In view of the fact that oxidative stress is a pathogenetic components of vascular complications in diabetes, it can be assumed that improvement of hemostasis parameters under the effect of enoxifol is determined by its antiplatelet and antioxidant activities.

Gastrointestinal transition and anti-diabetic effect of Isabgol husk microparticles containing gliclazide.

Isabgol husk with sodium alginate was formulated into gliclazide loaded microparticles which were characterized for particle size, swelling index, entrapment efficiency, in vitro release, release kinetics, stability, hypoglycemic effect, surface morphology, and gastrointestinal transition. The particle size in different formulations varied from 752.83 ± 0.630 to 872.03 ± 0.293 µm. It was analyzed by dissolution study that up to 98% of loaded gliclazide was released in simulated intestinal fluid (SIF, pH 7.4) within 8h. The formulations containing sodium alginate and Isabgol husk-sodium alginate showed bioequivalency with marketed sustained release tablets (Glizid MR 60(®)) in terms of release pattern. The drug maintained its integrity in terms of functional groups after fabrication in formulations as observed by FTIR analysis. The hypoglycemic effect of gliclazide loaded Isabgol husk-sodium alginate microparticles was found to be 37 ± 6.356% in terms of changes of blood glucose level from base glucose level (100%) in diabetic condition after 24h of oral administration and it was more than marketed conventional tablets (95.5 ± 3.286%). The retention of microparticles was observed in small intestine up to 10h during whole body X-ray imaging. The study revealed that microparticles composing of Isabgol husk may have the potential for regulating blood glucose level in diabetic animals with controlled release of gliclazide.

In vitro inhibition of metabolism but not transport of gliclazide and repaglinide by Cree medicinal plant extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Interactions between conventional drug and traditional medicine therapies may potentially affect drug efficacy and increase the potential for adverse reactions. Cree traditional healing is holistic and patients may use medicinal plants simultaneously with the conventional drugs. However, there is limited information that these medicinal plants may interact with drugs and additional mechanistic information is required. In this study, extracts from traditionally used Cree botanicals were assessed for their potential interaction that could alter the disposition of two blood glucose lowering drugs, gliclazide (Diamicron) and repaglinide (Gluconorm) though inhibition of either metabolism or transport across cell membranes. MATERIALS AND METHODS: The effect of 17 extracts on metabolism was examined in a human liver microsome assay by HPLC and individual cytochrome P450s 2C9, 2C19, 2C8 and 3A4 in a microplate fluorometric assay. Gliclazide, rhaponticin and its aglycone derivative, rhapontigenin were also examined in the fluorometric assay. The effect on transport was examined with 11 extracts using the intestinal epithelial Caco-2 differentiated cell monolayer model at times up to 180 min. RESULTS: Both blood glucose lowering medications, gliclazide and repaglinide traversed the Caco-2 monolayer in a time-dependent manner that was not affected by the Cree plant extracts. Incubation of the Cree plant extracts inhibited CYP2C9, 2C19, 2C8 and 3A4-mediated metabolism, and the formation of four repaglinide metabolites: M4, m/z 451-A, m/z 451-B and the glucuronide of repaglinide in the human liver microsome assay. Gliclazide caused no significant inhibition. Likewise, rhaponticin had little effect on the enzymes causing changes of less than 10% with an exception of 17% inhibition of CYP2C19. By contrast, the aglycone rhapontigenin showed the greatest effects on all CYP-mediated metabolism. Its inhibition ranged from a mean of 58% CYP3A4 inhibition to 89% inhibition of CYP2C9. While rhaponticin and the aglycone did not show significant effects on repaglinide metabolism, they demonstrated inhibition of gliclazide metabolism. The aglycone significantly affected levels of gliclazide and its metabolites. CONCLUSION: These studies demonstrate that the Cree plant extracts examined have the potential in vitro to cause drug interactions through effects on key metabolic enzymes.

Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.

The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE.

Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats.

Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic ß-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1ß (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes.

Protective effects of combined therapy of gliclazide with curcumin in experimental diabetic neuropathy in rats.

Diabetic neuropathy is the most common chronic complication of diabetes. The aim of the present study was to evaluate the protective effects of curcumin against neuropathy in gliclazide-treated diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (45 mg/kg). Diabetic animals were given gliclazide (10 mg/kg, orally) alone or combined with curcumin (100 mg/kg, orally) or gabapentin (30 mg/kg, intraperitoneally as a positive control). Behavioral responses to thermal (hot plate and tail flick) and mechanical (tail pinch) pain, and some biochemical tests (serum glucose, C-peptide, peroxynitrite, lipid peroxides, and tumor necrosis factor-α) were assessed after 5 consecutive weeks of daily treatment. Combined treatment of curcumin with gliclazide significantly increased hot-plate and tail-flick latencies in comparison with that of the diabetic control group. The threshold of mechanical hyperalgesia was also significantly elevated. Serum glucose and C-peptide levels were significantly increased in the combined treatment compared with the diabetic control group, whereas serum levels of peroxynitrite, lipid peroxide, and tumor necrosis factor-α production were significantly decreased. The data suggest that the combination of curcumin with gliclazide may protect against the development of diabetic neuropathy, with favorable effects with respect to the gliclazide/gabapentin combination.

Antidiabetic and antioxidant potentials of Euphorbia hirta leaves extract studied in streptozotocin-induced experimental diabetes in rats.

Euphorbia hirta, commonly known as asthma weed, is a popular folk remedy for the treatment of various ailments. Recent studies have indicated that plant has potent antioxidant properties. As part of an ongoing programme to validate the use of some reputed herbs in Indian traditional medicines, the present study was aimed to evaluate the antidiabetic and antioxidant potentials of E. hirta leaves in streptozotocin-induced experimental diabetes in rats. Oral administration of E. hirta leaves extract (300 mg/kg b.w./rat/day) for a period of 30 days indicated the antidiabetic nature of the leaves extract. Determination of the lipid peroxides, hydroperoxides, and both enzymatic and non-enzymatic antioxidants evidenced the antioxidant potential of the leaves extract. Assay of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT) and serum alkaline phosphatase (ALP) revealed the non-toxic nature of E. hirta leaves. The hypoglycemic activity of the leaves extract was comparable with gliclazide, a standard reference drug.

Beneficial effect of S-allylcysteine (SAC) on blood glucose and pancreatic antioxidant system in streptozotocin diabetic rats.

The aim of the present study was to evaluate the possible protective effects of S-allyl cysteine (SAC) on the antioxidant defense system of pancreas in streptozotocin(STZ) induced diabetes in rats. The levels of blood glucose and TBARS in plasma and pancreas were estimated in control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system, the level of reduced glutathione in plasma and pancreas and activities of superoxide dismutase and catalase were assayed in pancreatic tissue homogenate. The levels of glucose, TBARS and enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of SAC. The antidiabetic and antioxidant effect of SAC was compared with glyclazide, a well-known hypoglycemic drug. These findings suggest that SAC treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress.

Antidiabetic effect of S-allylcysteine: Effect on plasma and tissue glycoproteins in experimental diabetes.

The present study was conducted to investigate the effect of S-allylcysteine (SAC) on dearrangement in glycoprotein levels in the streptozotocin induced diabetic model. SAC (150 mg/kg b.w./day) was administered orally for 45 days to normal and diabetic rats. STZ-induced diabetic rats showed significant increase in blood glucose and glycoprotein components such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidneys of diabetic rats. Oral administration of SAC to diabetic rats for a period of 45 days normalized all the above-mentioned biochemical parameters. The antihyperglycemic effect of SAC was compared with glyclazide, a well-known antihyperglycemic drug. The present study indicates that SAC possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect.

Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats.

Resveratrol, a ubiquitous stress-induced phytoalexin, has demonstrated a wide variety of biological activities which make it a good candidate for the treatment of diabetes mellitus. The present study was aimed to evaluate its therapeutic potential by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. The daily oral treatment of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days demonstrated a significant (p<0.05) decline in blood glucose and glycosylated hemoglobin levels and a significant (p<0.05) increase in plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver and kidney tissues of diabetic rats were significantly (p<0.05) reverted to near normal levels by the administration of resveratrol. Further, resveratrol administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of resveratrol in diabetic rats. The obtained results were compared with glyclazide, a standard oral hypoglycemic drug. Thus, the modulatory effects of resveratrol on attenuating these enzymes activities afford a promise for widespread use for treatment of diabetes in the future.

[Effects of Tangweian granule on 5-HT(2A)R in rat model with diabetic gastroparesis].

OBJECTIVE: To observe the effects of Tangweian granule on 5-HT(2A)R in rat model with diabetic gastroparesis (DGP). METHOD: The rats with diabetic gastroparesis induced by injecting alloxan and giving 200% Radix Rehmanniae preparata were divided into four groups randomly: Tangweian high dosage group, Tangweian low dosage group, motilium control group and the model control group, 10 rats each group. Each group was irrigated with drugs during establishing the model. Additionally, we chose 10 rats by way of normal control group. Further more, Tangweian high dosage group were irrigated stomach with gliclazide 20 mg x kg(-1) and Tangweian granule 31.75 g x kg(-1); Tangweian low dosage group were irrigated stomach with gliclazide 20 mg x kg(-1) and Tangweian granule 15.88 g x kg(-1); motilium control group were irrigated stomach with gliclazide 20 mg x kg(-1) and motilium 3.75 mg x kg(-1) and the model control group were irrigated stomach with distilled water. Then the effects of Tangweian granule on 5-HT(2A)R were observed. RESULT: The curative group had better effects than the control group in lowering the blood sugar and the level of 5-HT(2A)R content (P < 0.01). And there was significant difference between the curative group and control group (P < 0.05). CONCLUSION: It is verified that Tangweian granule has obvious effects on lowering the blood sugar and improving the level of 5-HT(2A)R.

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.

BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes. EXPERIMENTAL APPROACH: A crossover controlled study was conducted in 21 healthy subjects. Each received gliclazide (80 mg) either alone or during 15 days treatment with St John's wort. The area under the plasma concentration-time curve (AUC(0-infinity)), apparent clearance (CL/F) and elimination half-life (t 1/2) of gliclazide and incremental changes in glucose and insulin AUC(0-4) were compared. CYP2C9*2 and CYP2C9*3 alleles were identified using PCR followed by restriction enzyme digestion analysis. KEY RESULTS: St John's wort significantly altered gliclazide pharmacokinetics in all except for four healthy subjects. The mean ratio and 90% confidence interval (CI) of gliclazide AUC(0-infinity) and CL/F were 0.67 (0.55-0.81) and 1.50 (1.24-1.81), respectively, after St John's wort treatment. St John's wort decreased gliclazide t (1/2), with mean ratio and 90% CI of 0.85 (0.74-0.93). There were no significant changes in glucose or insulin AUC(0-4) after St John's wort treatment and no significant differences according to CYP2C9 genotype. CONCLUSIONS AND IMPLICATIONS: Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.

Antidiabetic activity of an ethanol extract obtained from the stem bark of Psidium guajava (Myrtaceae).

This study analyzed the antidiabetic properties of an ethanol extract of the stem bark of Psidium guajava, an indigenous medicinal plant used to control diabetes in Indian System of Medicine. The anti-hyperglycaemic activity of this plant on blood glucose levels of normal, normal glucose loaded (OGTT) and alloxan-induced hyperglycaemic rats was evaluated. The results showed that ethanol stem bark extract exhibited statistically significant hypoglycaemic activity in alloxan-induced hyperglycaemic rats but was devoid of significant hypoglycaemic effect in normal and normal glucose loaded rats (OGTT).

Effect of aqueous extract of Cyamopsis tetragonoloba Linn. beans on blood glucose level in normal and alloxan-induced diabetic rats.

Effect of feeding orally the aqueous extract of beans of Cyamopsis tetragonoloba was investigated on fasting blood glucose levels in glucose loaded, normal and alloxan-induced diabetic rats and compared with gliclazide, a reference drug. The aqueous extract of beans at 250 mg/kg body wt significantly lowered blood glucose levels in alloxan-induced diabetic rats within 3 hr of administration. Continued administration of the extract at the same dose daily for 10 days produced statistically significant reduction in the blood glucose levels while marginal activity was seen in normal and glucose-loaded rats.

Hypoglycaemic activity of Alpinia galanga rhizome and its extracts in rabbits.

This investigation was carried out to study effects of Alpinia galanga rhizome on blood glucose levels. In normal rabbits, powdered rhizome and its methanol and aqueous extracts significantly lowered the blood glucose. Gliclazide also produced a significant decrease in blood glucose in the rabbits. In alloxan-diabetic rabbits, A. galanga and its methanol and aqueous extracts did not produce significant reduction in blood glucose. The hypoglycaemic effect of A. galanga in normal rabbits was comparable to gliclazide. The rhizome was found to contain high levels of certain minerals. Acute toxicity and behavioral studies revealed no visible signs of toxicity and any abnormal behavior in rabbits even at high doses. It is concluded that A. galanga produces fall in blood glucose levels in normal rabbits and the principles, both organic and inorganic, are extractable in methanol and water.