Govindasamy Chandramohan

Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats

Abstract Objective The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats. Results The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal. Conclusion The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.

Antihypertensive effect of Melothria maderaspatana leaf fractions on DOCA-salt-induced hypertensive rats and identification of compounds by GC-MS analysis.

The present study was designed to investigate the antihypertensive effect of Melothria maderaspatana leaf fractions on deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats and to identify compounds from the active fraction by GC–MS analysis. Administration of DOCA salt significantly increased the systolic and diastolic blood pressure compared to sham-operated control rats. When treated with chloroform (CFM), ethyl acetate (EAFM) or methanol fractions of M. maderaspatana (MFM), EAFM alone significantly lowered the systolic and diastolic blood pressure. The levels of magnesium and copper significantly increased in plasma and decreased in tissues while the zinc level significantly increased in plasma and tissues, and administration of EAFM brought these parameters back to sham-operated control levels. By GC–MS analysis, phytochemicals such as coumarin, vallinic acid, p-coumaric acid, gallic acid, caffeic acid, and ferulic acid were identified in EAFM. In conclusion, the EAFM controls blood pressure in DOCA-salt hypertensive rats and reverts the metabolic alterations in magnesium, copper and zinc.

Antihyperlipidemic effect of Melothria maderaspatana leaf extracts on DOCA-salt induced hypertensive rats.

OBJECTIVE To investigate the antihyperlipidemic effect of crude ethanolic extract of Melothria maderaspatana (M. maderaspatana) leaf (CEEM) on deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS A midscapular incision was made on each rat and the left kidney was excised after ligation of the renal artery. The surgical wound was closed using an absorbable suture. After one week recovery period, hypertension was induced by subcutaneous injection of DOCA-salt solution, twice a week, and the rats received a 1% sodium chloride solution as drinking water throughout the experimental period. CEEM or nifedipine was administered orally once a day for 6 weeks. RESULTS In DOCA-salt hypertensive rats, the level of plasma and tissues of total cholesterol (TC), triglycerides (TG), free fatty acids (FFA) and phospholipids (PL) significantly increased and administration of CEEM significantly reduced these parameters towards normality. Further, the levels of low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) significantly increased while high density lipoprotein-cholesterol (HDL-C) decreased in hypertensive rats and administration of CEEM brought these parameters to normality which proved their antihyperlipidemic action. Histopathology of liver, kidney and heart on DOCA-salt induced rats treated with CEEM showed reduced the damages towards normal histology. CONCLUSIONS These findings provided evidence that CEEM was found to be protecting the liver, kidney and heart against DOCA-salt administration and the protective effect could attribute to its antihyperlipidemic activities.

Protective effect of Cardiospermum halicacabum leaf extract on glycoprotein components on STZ–induced hyperglycemic rats

OBJECTIVE To investigate the protective role of Cardiospermum halicacabum (C. halicacabum) leaf extract on glycoprotein metabolism in streptozotocin (STZ)-induced diabetic rats. METHODS Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ. The C. halicacabum leaf extract (CHE) was administered orally to normal and STZ-diabetic rats for 45 days. The effects of C. halicacabum leaf extract (CHE) on plasma and tissue glycoproteins (hexose, hexosamine, fucose and sialic acid) were determined. RESULTS The levels of plasma and tissues glycoproteins containing hexose, hexosamine and fucose were significantly increased in STZ-induced diabetic rats. In addition, the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ-induced diabetic rats. After administration of CHE to diabetic rats, the metabolic alteration of glycoprotein reverted towards normal levels. CONCLUSIONS The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

Protective effect of morin on cardiac mitochondrial function during isoproterenol-induced myocardial infarction in male Wistar rats

Abstract Altered mitochondrial function and free radical-mediated tissue damage have been suggested as an important pathological event in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of morin on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Myocardial infarction (MI) in rats was induced by ISO (85 mg/kg) at an interval of 24 hours for 2 days. Morin was given to rats as pre-treatment for 30 days orally using an intragastric tube. ISO-treated rats showed a significant elevation of mitochondrial thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (HP) level and pre-treatment with morin significantly prevented the increase of TBARS and HP level to near normality. The level of enzymic and non-enzymic antioxidants was decreased significantly in ISO-treated rats and pre-treatment with morin significantly increased the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and reduced glutathione to normality. The activities of mitochondrial enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were decreased significantly in ISO-treated myocardial ischemic rats and upon pre-treatment with morin restored these enzymes activity to normality. In addition, the decreased activities of cytochrome-C oxidase and NADH-dehydrogenases were observed in ISO-treated rats and pre-treatment with morin prevented the activities of cytochrome-C oxidase and NADH-dehydrogenase to normality. Pre-treatment with morin favorably restored the biochemical and functional parameters to near normal indicating morin to be a significant protective effect on cardiac mitochondrial function against ISO-induced MI in rats.

Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin-diabetic rats

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3‐hydroxymethyl xylitol (3‐HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long‐term effect of 3‐HMX in type 2 diabetic rats on carbohydrate metabolism was investigated, and its antihyperglycemic effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437–443). In this study we investigated the effect of 3‐HMX on plasma and tissue lipid profiles in streptozotocin‐induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180–200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The normal and diabetic rats were treated with 3‐HMX (40 mg/kg BW/day) for 45 days. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids were assayed in the plasma besides lipoprotein‐cholesterol (high‐density lipoprotein‐cholesterol (HDL‐C), low‐density lipoprotein‐cholesterol (LDL‐C), and very low density lipoprotein‐cholesterol (VLDL‐C)) and tissues (liver, kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL‐C and VLDL‐C in plasma only) levels increased in plasma and tissues significantly, whereas plasma HDL‐C significantly decreased in diabetic rats. Treatment with 3‐HMX or glibenclamide reversed the above‐mentioned changes and improved toward normalcy. Histological study of liver also confirmed the biochemical findings. Thus administration of 3‐HMX is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.

Protective effect of Melothria maderaspatana leaf fraction on electrolytes, catecholamines, endothelial nitric oxide synthase and endothelin-1 peptide in uninephrectomized deoxycorticosterone acetate–salt hypertensive rats

This study was designed to investigate the protective effect of ethyl acetate fraction of Melothria maderaspatana (EAFM) leaf on electrolytes, catecholamines, endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) peptide in uninephrectomized deoxycorticosterone acetate (DOCA)–salt hypertensive rats. Administration of DOCA–salt significantly increased the systolic and diastolic blood pressure and treatment with EAFM significantly lowered the blood pressure. In DOCA–salt rats, the levels of sodium and chloride increased significantly while potassium level decreased and administration of EAFM brought these parameters to normality. The levels of epinephrine and norepinephrine increased significantly in DOCA–salt rats and administration of EAFM significantly decreased these parameters to normality. DOCA–salt hypertensive rats exhibited significantly decreased L-arginine and nitrite + nitrate levels and administration of EAFM brought these parameters to normality. DOA–salt hypertensive rats showed down-regulation of eNOS and up-regulation of ET-1 protein expressions in heart and kidney, and treatment with EAFM prevented down-regulation of eNOS and significantly down-regulated the ET-1 protein expressions. In conclusion, EAFM provides good blood pressure control by enhancing potassium and decreasing sodium levels, decreasing levels of epinephrine and norepinephrine, and preventing down-regulation of eNOS and significantly down-regulating ET-1 protein expression.

In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis

Impaired wound healing is one of the serious problems among the diabetic patients. Currently, available treatments are limited due to side effects and cost effectiveness. In line with that, we attempted to use a natural source to study its potential towards the wound healing process. Therefore, Alternanthera sessilis (A. sessilis), an edible and medicinal plant, was chosen as the target sample for the study. During this investigation, the wound closure properties using stem extract of A. sessilis were analyzed. Accordingly, we analyzed the extract on free radical scavenging capacity and the cell migration of two most prominent cell types on the skin, human dermal fibroblast (NHDF), keratinocytes (HaCaT), and diabetic human dermal fibroblast (HDF-D) to mimic the wound healing in diabetic patients. The bioactive compounds were identified using gas chromatography-mass spectrometry (GC-MS). We discovered that the analysis exhibited a remarkable antioxidant, proliferative, and migratory rate in NHDF, HaCaT, and HDF-D in dose-dependent manner, which supports wound healing process, due to the presence of wound healing associated phytocompounds such as Hexadecanoic acid. This study suggested that the stem extract of A. sessilis might be a potential therapeutic agent for skin wound healing, supporting its traditional medicinal uses.

Galangin controls streptozotocin-caused glucose homeostasis and reverses glycolytic and gluconeogenic enzyme changes in rats

Abstract Galangin is a natural compound with anticancer, anti-inflammatory, and antioxidant properties. However, the ameliorating effect of streptozotocin (STZ)-induced glucose homeostasis has not yet been evaluated. Hence, this study was aimed at exploring the role of galangin in STZ-induced glucose homeostasis, glycolytic and gluconeogenic enzyme changes in rats. STZ-treated rats were characterised by increased plasma glucose and glycosylated haemoglobin and decreased plasma insulin and haemoglobin compared with the normal cage. Administration of galangin to STZ-treated rats effectively reversed the adverse biochemical and haematological changes. Significant alterations in glycogen levels as well as glycolytic and gluconeogenic enzyme activities were witnessed in STZ-treated rats, and these changes were reversed upon treatment with galangin. The compound exerts potent anti-hyperglycemic effects by regulating the glucose homeostasis and reversing the glycolytic and gluconeogenic enzyme changes in rats. However, the exact mechanism through which galangin prevents diabetic complications needs to be studied in detail.

Antihyperglycemic Effect of Camel Milk in Streptozotocin- Diabetic Rats

Results: Subjects with diabetes showed a signifi cant reduction in Forced Vital Capacity (FVC) and Forced Expiratory Volume in the First Second (FEV(1)) relative to their matched controls. We observed a signifi cantly negative correlation between duration of disease and pulmonary function, as measured by FEV(1) (r = 0.258, p = 0.04), FVC (r = 0.282, p = 0.28), and the middle half of the FVC (FEF(25-75%)) (r = 0.321, p = 0.014).Camel milk is different from other ruminant milk; having low cholesterol; low sugar; high minerals especially Zinc; high vitamin C; low protein and large concentrations of insulin. In Saudi Arabia, camel milk is traditionally used for many medical approaches. The study was designed to investigate the antihyperglycemic effect of camel milk on streptozotocin (STZ)-diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. Diabetic rats showed increase of plasma glucose and glycosylated haemoglobin (HbA1c) and a decrease of plasma insulin and haemoglobin (Hb). Activities of gluconeogenic enzymes such as glucose 6-phosphatase, fructose 1, 6-bisphosphatase increased and glucokinase, glucose 6-phosphate dehydrogenase decreased in the liver along with glycogen. Oral administration of camel milk 250 ml for 45 days prevented the above changes and improved towards normalcy. These results indicate that camel milk possesses antihyperglycemic effect on long-term treatment and its effect was comparable with glibenclamide. Key words: camel milk, streptozotocin, glucose, insulin, antihyperglycemic effect, Saudi Arabia