EFFECT OF METHYL-Î’-CYCLODEXTRIN COMPLEXATION ON THE HYPOGLYCEMIC AND HYPOLIPIDEMIC EFFECTS OF KHELLIN: EXPERIMENTAL STUDY

Objective: The present work tackled the development and evaluation of inclusion complex of khellin (KH) and methyl-β-cyclodextrin (MβCD). In addition, it tested its possible hypoglycemic and hypolipidemic effects.Methods: Inclusion complexes of KH-MβCD in the presence of water-soluble polymer were prepared by freeze drying (FD), co-evaporation (EV) and kneading methods (KN). The selected ternary complex was characterized by Fourier transform infrared spectrophotometry (FTIR), x-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy [1]. Assessment of the hypoglycemic effect of the selected ternary complex versus the standard drug metformin was studied. Two different doses of the ternary complex were administered orally to streptozotocin (STZ)-induced type 2diabetic rats. Their hypoglycemic and hypolipidemic effects were evaluated by measuring the fasting blood glucose level (BGL), total cholesterol (TC) and triglycerides levels (TG) along the study period.Results: The FD complex showed the highest drug dissolution rate. All the performed characterization analysis confirmed the formation of a KH-MβCD inclusion complex. The in vivo study declared that both doses showed a marked hypoglycemic and hypolipidemic effects compared to metformin.Conclusion: In conclusion, this study points for the first time that the complexation of KH with MβCD could notably improve the dissolution rate and hence the bioavailability of KH. Moreover, this study demonstrated that this compound has a hypoglycemic and hypolipidemic effect. Thus, it can be a promising natural supportive treatment in type 2 diabetes mellitus (T2DM).Â

HEPATOPROTECTIVE ACTIVITY OF MONASCUS PURPUREUS (RED RICE YEAST) IN DIABETIC RATS ALONE OR IN COMBINATION WITH PIOGLITAZONE: AN EFFECT MEDIATED THROUGH CYTOKINES, ANTIOXIDANTS AND LIPID BIOMARKERS

Objective: Diabetes induces many complications such as cardiovascular problems, cataracts, kidney damage and polyneuropathy. Streptozotocin (STZ) induced diabetes is considered one of the most common animal models in rats. The present study investigated the effects of Monascus purpureus (MP) alone or in combination with pioglitazone on glucose level and on liver in streptozotocin (STZ) diabetic rats.Methods: In this study were divided into five experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with Monascus purpureus (500 mg/kg B. W, oral), treated STZ-diabetic with pioglitazone (10 mg/kg B.W., oral) and treated STZ-diabetic with MP (250 mg/kg B. W, oral)+pioglitazone (10 mg/kg B.W., oral)). Treatment continued for 14 d then blood sampling was done to assess blood glucose. At the end of the study, the animals were fasted overnight, anesthetized with sodium pentobarbital (60 mg/kg i.p.), and sacrificed to collect tissues samples (liver, pancreases).Results: Throughout the experimental period, all treatments significantly (P<.05) lowered serum glucose, triglycerides, cholesterol, c-peptide and IL-6. In addition, hepatic cholesterol and triglycerides levels were also lowered. Moreover, the treated diabetic rats showed higher activity of reduced glutathione (P<.05) in the liver compared with the diabetic control rats and inhibited diabetes induced elevation in the level of malondialdehyde in liver.Conclusion: The results of this study clearly demonstrated that MP act by many ways, including anti-hyperglycemic, antioxidant effects and pancreatic β-cell protection. From these points, it seems that MP may be a useful supplement to alleviate the development of diabetes and its complications

ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

Antioxidant Potential of Spirulina platensis

The present study aimed to examine the protective role of Spirulina platensis (S. platensis) against arsenic-induced testicular oxidative damage in rats. Arsenic (in the form of NaAsO2 at a dose of 6.3 mg/kg body weight for 8 weeks) caused a significant accumulation of arsenic in testicular tissues as well as a decrease in the levels of testicular superoxide dismutase (SOD), catalase (CAT), reduced glutathione, and zinc. Moreover, it significantly decreased plasma testosterone, luteinizing hormone (LH), triiodothyronine (T3), and thyroxine (T4) levels and reduced sperm motility and sperm count. Arsenic (AS) led to a significant increase in testicular malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), nitric oxide (NO), and sperm abnormalities. S. platensis at a dose of 300 mg/kg was found to attenuate As-induced oxidative stress, testicular damage, and sperm abnormalities by its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect the testicular tissue from arsenic intoxication

Protective Effects of Pioglitazone on Dextran Sodium Sulphate-Induced Colitis in Rats: Effects of Pioglitazone on Dextran Sodium Sulphate-Induced Colitis

The aim of the present study is to investigate the preventive effect of pioglitazone on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Sprague-Dawley rats weighing 180-200 g were randomized into four groups. Rats of the 1st group received only saline and served as normal group. Colitis was induced in the remaining 3 groups by 1.5% DSS administered in drinking water for 8 days. Group 2 received only saline p.o. for 30 days and served as DSS control group. Groups 3 and 4 received pioglitazone (PIO; 10 mg/kg/day, p.o.) and sulfasalazine (SUL; 300 mg/kg) respectively for 30 days. All animals were sacrificed 24 h after the last treatment. Serum levels of interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-17 (IL-17) were measured. Levels of tumor necrosis factor-α (TNF-α), reduced glutathione (GSH) and malondialdhyde (MDA), were measured in colon tissue. Significant elevation in GSH levels and reduction in MDA and TNF-α levels in colon tissue were observed in pioglitazone and sulfasalazine treated group when compared with the DSS control group. Significant elevation in serum IL-2 and reduction in serum IL-6 and IL-17 were observed when compared with the DSS control group. Pioglitazone reduced DSS-induced colitis possibly via reduction of MDA, TNF-α, IL-6, and IL-17 levels

Alleviation of haloperidol induced oxidative stress in rats: Effects of sucrose vs grape seed extract

Haloperidol (HP) is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. HP is known to induce oxidative stress due to increased turnover of dopamine. The aim of the present study was to investigate the effect of sucrose (1 and 5 mg/kg; p.o.) and grape seed extract (GSE; 100, 200 and 400 mg/kg; p.o.) on the oxidative stress induced in rats by HP (1 mg/kg; p.o.) in the liver and the brain tissues. Oxidative stress was induced by injection of HP for 14 consecutive days which was concurrently administered with sucrose and GSE. Liver and brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels were determined in the brain and liver. Results of the present study revealed that HP-treated rats showed elevated levels of NO in the brain and MDA in the brain and liver. HP-treated rats showed also decreased levels of NO levels in the liver and GSH in the brain and liver. Treatment of HP-treated rats with GSE reversed all the oxidative stress markers in both the brain and liver due to its potent antioxidant property. On the other hand, sucrose attenuates the levels of NO in the brain and liver and the brain levels of MDA and GSH. It can be concluded that both GSE (a potent anti-oxidant) and sucrose (as a source of energy) have beneficial impacts on the brains of HP-treated rats. However, GSE is more potent in alleviating the oxidative stress associated with HP in the liver

Grape seed extract attenuates hyperglycaemia-induced in rats by streptozotocin

The current study aimed to investigate the possible beneficial effects of grape seed extract (GSE) on some metabolic and biochemical changes associated with streptozotocin (STZ; 50 mg/kg; i.p.)-induced hyperglycaemia in male rats. Blood samples were used to determine serum levels of glucose, insulin, total cholesterol (TC) and triglycerides (TG). Some biochemical markers for oxidative stress viz., serum lipid peroxides level (measured as malondialdehyde; MDA) and total antioxidant capacity as well as serum nitric oxide (NO) level were assessed. Hyperglycaemic animals received GSE (100 and 300 mg/kg/day) orally on daily basis for 28 consecutive days and their effects were determined 24 h after the administration of the last dose. Results of the present study revealed that STZ-induced hyperglycaemia is associated with decreased serum insulin level with increased levels of TC and TG. Hyperglycaemia was also associated with increased level of serum MDA together with decreased total antioxidant capacity and level of serum NO. GSE succeeded to improve the serum glucose level in STZ-treated rats in a dose dependent manner. It also showed a restoration of the increased serum level of TC, TG and MDA and of the suppressed insulin and total antioxidant capacity as well as the decreased plasma level of NO. From our results it can be concluded that GSE has beneficial effects against the biochemical changes associated with STZ-induced hyperglycaemia. These beneficial effects might be related to the ability of GSE to improve hyperglycaemia in addition to its anti-oxidant property

Protective effects of ursodeoxycholic acid on ceftriaxone-induced hepatic injury in rats

Ceftriaxone is a broad-spectrum semisynthetic cephalosporin antibiotic that causes partial damage in the liver manifested by transient elevation in some biochemical parameters. In this study, our aim was to investigate the use of ursodeoxycholic acid (UDCA) in prevention of the hepatotoxic effect and biochemical changes induced by ceftriaxone in rats. Rats were divided into six groups (control, UDCA 20 mg/kg, ceftriaxone 180 mg/kg, UDCA + ceftriaxone 180 mg/kg, ceftriaxone 360 mg/kg, and UDCA + ceftriaxone 360 mg/kg). Ceftriaxone was injected intraperitoneally, and UDCA was given orally daily for four consecutive weeks. Then liver functions (serums AST, ALT, ALP, direct bilirubin, and total protein) were assessed. Histopathological examination was performed. Treatment of animals with ceftriaxone caused elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as total bilirubin level. These elevations in liver enzymes were decreased by combination ceftriaxone with UDCA. In addition, ceftriaxone caused a significant increase in malondialdehyde (MDA) and nitric oxide (NO) content but significant decrease in glutathione (GSH) content. Combination of UDCA and ceftriaxone resulted in a significant decrease in MDA, NO content and significantly elevated GSH content. It could be concluded that UDCA acts as an effective hepatoprotective agent against liver dysfunction caused by ceftriaxone, and this effect might be related to its antioxidant properties. Hepatic functions should be monitored, and the dose should be adjusted during ceftriaxone therapy

In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca

Context: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear. Objectives: Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds. Materials and methods: A bio-guided protocol based on the evaluation of α‐glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks. Results: Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-β-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3β,16β,20(R)-trio1-3-O-β-d-glucopyranoside; a furostanol saponin, (3) 26-(O-β-d-glucopyranosyl)-22-O-methylfurost-5-ene-3β,26-diol-3-O-β-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC50 = 3.12 ± 0.17 and 1.04 ± 0.02 μg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively. Discussion and conclusions: We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications

Modulation of the pharmacological properties of meloxicam by octreotide in rats

The purpose of this study was to investigate the anti-inflammatory, analgesic, antipyretic and antiulcer properties of somatostatin analogue octreotide (10 and 100 μg/kg) and its influence on the effect of NSAID meloxicam (1 and 2 mg/kg) in rats. Carrageenan-induced rat paw oedema was used as an acute anti-inflammatory model as well as adjuvant-induced arthritis as a chronic model. Hot plate test on rats and acetic acid (0.6%) writhing test were used as acute analgesic models while the plantar test using an infrared beam directed to the paw of arthritic rats was used as a chronic analgesic model. Antipyretic effect was evaluated using Brewer’s yeast (44%) induced hyperthermia in rats while pylorus ligation was used as a model to evaluate the ulcerogenic effects. Meloxicam, octreotide and their combinations administered subcutaneously showed anti-inflammatory effects in both acute and chronic models. Only the high doses of meloxicam and octreotide showed significant analgesic effect in the hot plate test, while all doses showed significant analgesic effects in the acetic acid-induced writhing test and in the plantar test. In yeast-induced hyperthermia, only meloxicam has an antipyretic effect. Meloxicam resulted in profound gastric lesions and exerted deleterious effects on the gastric mucosa in pyloric-ligated rats. Octreotide did not cause any harmful effect on the gastric mucosa, besides; octreotide attenuated the harmful ulcerogenic effects of meloxicam when administered in combination with it. Both meloxicam and octreotide and their combination significantly decreased the malondialdehyde (MDA) content in the arthritic rats indicating their antioxidant effects