Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats

Context: Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus. Objective: This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats. Materials and methods: Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10 mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed. Results: This study showed that MC caused a significant reduction of serum glucose (135.99 ± 6.27 and 149.79 ± 1.90 vs. 253.40* ± 8.18) for prophylaxis and treatment respectively, fructosamine (0.99 ± 0.01 and 1.01 ± 0.04 vs. 3.04 ± 0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13 ± 0.08 and 1.19 ± 0.05 vs. 1.48 ± 1.47) and pancreatic malondialdehyde content (p < 0.05). While it induced a significant increase of serum insulin (3.41 ± 0.08 and 3.28 ± 0.08 vs. 2.39 ± 0.27), HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content (p < 0.05) and improved histopathological changes of the pancreas. It also increased glucose uptake by diaphragms of normal (12.17 ± 0.60 vs. 9.07 ± 0.66) and diabetic rats (8.37 ± 0.28 vs. 4.29 ± 0.51) in the absence and presence of insulin (p < 0.05). Conclusions: Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is used for prophylaxis or treatment

Novel combination of thymoquinone and resveratrol enhances anticancer effect on hepatocellular carcinoma cell line

Hepatocellular carcinoma remains one of the most dominant malignancies worldwide. Neutraceuticals have become under focus in anticancer treatment. Resveratrol is one of the major components of Polygonum Cuspidatum and is known as chemo-preventive agent. Thymoquinone is one of the most potent constituents in Nigella Sativa and has many medicinal effects. The aim of the present study is to investigate the combined effect of thymoquinone and resveratrol on treatment of hepatocellular carcinoma cells (HepG2). We evaluated the effect of thymoquinone and resveratrol separately and in combination on HepG2. Cell viability, caspase-3 activity, glutathione and malondialdehyde content were determined. The IC50 values of thymoquinone and resveratrol were (46 μM and 64.5 μM) respectively, where each showed potent anti-tumor activity on HepG2. The cell viability was 47.2% and 49.9% respectively. Comparing to the control group, treatment with thymoquinone and resveratrol increased caspase-3 enzyme by 77% and 98.5% respectively, while content of glutathione decreased by 22.8% and 35.6% while malondialdehyde content decreased by 18% and 29.6% correspondingly. The combination (thymoquinone + resveratrol) affected the cell viability leading to further decrease by 9.9% and 12.6%. The content of caspase-3 increased by 89% and 67.5% while the glutathione content had further decrease by 25.6% and 12.8%. Malondialdehyde content decreased by 32.3% and 20.7% all are comparing to thymoquinone and resveratrol separate treatment.Thymoquinone and resveratrol combination showed significant cell inhibition and increase in caspase-3 indicating cell apoptosis. Both drugs raised reactive oxygen species leading to decrease of glutathione and minor effect on lipid peroxidation, all these results give a new promising combination with enhanced anticancer effect. Keywords: HepG2 cell line, Neutraceuticals, Thymoquinone, Resveratro

Study of the Possible Prophylactic Effect of Hibiscus Sabdariffa Extract on Experimental Hypertension in Rats

Background: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa (HS) is a plant known in many countries and is consumed as hot and cold drinks. Aim of the work: The present study was designed to assess the possible prophylactic effect of aqueous extract of HS on experimental hypertension in rats. Methods: Renovascular hypertension was induced in rats by left renal artery ligation with 4-0 sterile surgical silk. Sham-operated rats served as control. The animals were divided into: control group, sham group, hypertensive group, hypertensive group pretreated with HS (250mg/kg/day) given orally 30 days before ligation of left renal artery and 30 days after ligation. Results: Pretreatment of hypertensive group with HS extract prevented the development of hypertension and significantly reduced heart rate with significant decrease in serum levels of cholesterol, triglyceride and low density lipoprotein cholesterol while it increased significantly serum high density lipoprotein cholesterol and nitric oxide levels as compared to non-treated hypertensive group. Hibiscus sabdariffa also prevented the decrease in aortic reduced glutathione content and superoxide dismutase enzyme activity while it did not cause any significant change in serum levels of sodium or potassium as compared to non-treated hypertensive group. Conclusion: The present study showed that HS prevented the development of hypertension in an experimental model of hypertension which may be attributed to its negative chronotropic, nitric oxide preserving and antioxidant effects and is not related to serum electrolytes

Effects of Lorcaserin on Hypothalamo-PituitaryOvarian Axis in Female Rats

The current study aimed to investigate the effect of lorcaserin on estrous cyclicity, reproductive hormones and folliculogenesis in female rats. Groups were assigned as control group and lorcaserin (5,10 and 30 mg/kg/day) groups. Estrous cycles were disturbed in 40%, 40% and 100% of lorcaserin (5, 10 or 30 mg/kg) treated rats, respectively. Lorcaserin (5, 10 or 30 mg/kg) increased estradiol and reduced LH. Minimal edema with congested vessels was observed in the stroma of ovarian sections. Uterine sections depicted hyperplasia in the endometrium. These findings suggest that lorcaserin should be used with caution in women of child bearing potential until complete safety data are available

The anorectic agent, lorcaserin, disturbs estrous cyclicity and produces endometrial hyperplasia without affecting ovarian population in female rats

Life Sciences Volume 183, 15 August 2017, Pages 69-77Aims The present study aims to investigate the effect of the new anorectic agent, lorcaserin, on estrous cyclicity, reproductive hormones and folliculogenesis in female mature rats. Materials and methods Rats were divided into four groups; Group i: control group. Group ii-iv: rats treated with lorcaserin (5, 10 or 30 mg/kg/day, p.o.), respectively. The treatment continued for 28 days. Key findings Lorcaserin (5 or 10 mg/kg) caused estrous cycle disturbance in 40% of treated rats while the high dose (30 mg/kg) produced disturbances in 100% of the treated rats. Lorcaserin (5–30 mg/kg) altered some of female hormones where it enhanced estradiol but reduced luteinizing hormone. Minimal edema with congested vessels was observed in the medulla of ovarian sections. Further, epithelial and uterine sections showed hyperplasia. Significance Taken together, the present results demonstrated that lorcaserin affected some reproductive hormones, disturbed estrous cyclicity and induced histopathological changes in the ovaries and uteri without affecting the ovarian populations. Therefore, lorcaserin should be used with caution in women of child bearing potential until adequate clinical safety data are available

PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals

Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms

PARP inhibition ameliorates nephropathy in an animal model of type 2 diabetes: focus on oxidative stress, inflammation, and fibrosis

Poly(ADP-ribose) polymerase (PARP) enzyme contributes to nephropathy, a serious diabetic complication which may lead to end-stage renal disease. The study aims to investigate the effect of PARP over-activation on kidney functions in a type 2 diabetic rat model. The study also tests the therapeutic use of PARP inhibitors in diabetic nephropathy. Type 2 diabetes was induced in adult male rats by highfructose/high-fat diet and low streptozotocin dose. Then, the PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for 10 weeks. At the end, urine samples were collected to measure urine creatinine, albumin, and total proteins. PARP activity, superoxide dismutase (SOD) activity, and nitrite content were measured in kidney tissue homogenate. Glucose, fructosamine, insulin, and tumor necrosis factor-alpha (TNF-α) were measured in serum. Furthermore, histological studies, collagen deposition, and immunofluorescence of nuclear factor kappa B (NFκB) and transforming growth factor beta1 (TGF-β1) were carried out. PARP enzyme activity was significantly higher in the diabetic group and was significantly reduced by 4-AB administration. Diabetic animals had clear nephropathy indicated by proteinuria and increased albumin excretion rate (AER) which were significantly decreased by PARP inhibition. In addition, PARP inhibition increased creatinine clearance in diabetic animals and reduced renal TGF-β1 and glomerular fibrosis. Moreover, PARP inhibition alleviated the elevated serum TNF-α level, renal NFκB, nitrite, and the decrease in SOD activity in diabetic animals. However, PARP inhibition did not significantly affect neither hyperglycemia nor insulin sensitivity. PARP enzyme inhibition alleviates diabetic nephropathy through decreasing inflammation, oxidative stress, and renal fibrosi