Khalid S. Al-Numair

Effect of carvacrol on hepatic marker enzymes and antioxidant status in d-galactosamine-induced hepatotoxicity in rats

Carvacrol (2‐methyl‐5‐(1‐methylethyl)‐phenol) is a predominant monoterpenic phenol which occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. This study was designed to investigate the hepatoprotective and antioxidant properties of carvacrol on d‐galactosamine (D‐GalN)‐induced hepatotoxicity and oxidative damage in male albino Wistar rats. D‐GalN hepatotoxic rats exhibited elevation in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma‐glutamyl transpeptidase, and lipidperoxidative markers such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides. Activities of enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and the levels of non‐enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma, erythrocytes, liver, and kidney decreased in the hepatotoxic rats. Oral administration of carvacrol for 21 days brought these parameters towards normal. The biochemical observations were supported by histological studies of rat liver and kidney tissues. These results suggest that carvacrol could afford a significant hepatoprotective and antioxidant effect against D‐GalN‐induced rats.

Pharmacological effect of carvacrol on d-galactosamine-induced mitochondrial enzymes and DNA damage by single-cell gel electrophoresis

The present study aimed at investigating the effect of carvacrol on hepatic mitochondrial enzyme activities and DNA damage in d-galactosamine (d-GalN)-induced hepatotoxicity in male albino Wistar rats. The activities of hepatic mitochondrial enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase significantly decreased in d-GalN-hepatotoxic rats, and administration of carvacrol brought these parameters towards normality. In d-GalN-hepatotoxic rats, the hepatic mitochondrial concentration of thiobarbituric acid reactive substances significantly increased, and administration of carvacrol significantly reduced them towards normality. Furthermore, the activities of enzymatic antioxidants such as superoxide dismutase and glutathione peroxidase and the levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione decreased significantly in the liver mitochondria. Administration of carvacrol returned the enzymatic and non-enzymatic antioxidants towards normality. d-GalN-hepatotoxic rats had increased DNA damage, which administration of carvacrol significantly decreased. These results suggest that carvacrol has liver mitochondrial antioxidant properties and possesses a defensive effect against mitochondrial enzymes and DNA damage in d-GalN-induced rats.

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.

Protective Effect of Carvacrol on Oxidative Stress and Cellular DNA Damage Induced by UVB Irradiation in Human Peripheral Lymphocytes

Exposure to ultraviolet B (UVB; 280‐320 nm) radiation induces the formation of reactive oxygen species (ROS) in the biological system. In this study, we examined the protective effect of carvacrol on UVB‐induced lipid peroxidation and oxidative DNA damage with reference to alterations in cellular an‐tioxidant status in human lymphocytes. A series of in vitro assays (hydroxyl radical, superoxide, nitric oxide, DPPH (2,2‐Diphenyl‐1‐picryl hydrazyl), and ABTS (2,2‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid) radical scavenging assays) demonstrate antioxidant property of carvacrol in our study. UVB exposure significantly increased thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHPs), % tail DNA and tail moment; decreased % cell viability and antioxidant status in UVB‐irradiated lymphocytes. Treatment with carvacrol 30 min prior to UVB‐exposure resulted in a significant decline of TBARS, LHP, % tail DNA, and tail moment and increased % cell viability as carvacrol concentration increased. UVB irradiated lymphocytes with carvacrol alone (at 10 μg/mL) gave no significant change in cell viability, TBARS, LHP, % tail DNA, and tail moment when compared with normal lymphocytes. On the basis of our results, we conclude that carvacrol, a dietary antioxidant, mediates its protective effect through modulation of UVB‐induced ROS.

Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

ABSTRACT Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40 mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8 mg/kg BW) or glibenclamide (600 µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats. Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide. Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.

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.

Influence of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, on glycoprotein components 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 antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.

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.

Antidiabetic and hypolipidemic effects of Ceylon cinnamon (Cinnamomum verum) in alloxan-diabetic rats

The objective of this study was to examine the effects of increasing doses of Ceylon cinnamon’s aqueous extract on fasting plasma glycemic and lipidemic profiles, as well as body weight gain, food intake and food efficiency ratio (FER) in alloxan-diabetic rats. Cinnamon extract was administered to rats at different dosages (200, 400, 600 and 1200 mg/kg bw) for thirty days followed by a fifteen day wash out period. After thirty days, the administration of diabetic rats with the lowest dose (200 mg/kg bw) of cinnamon extracts was the most efficient in affecting significant (P < 0.05) reduction in the levels of fasting blood glucose (FBG), but no hypoglycaemic activity was observed in the untreated diabetic control rats. Moreover, cinnamon treatment significantly (P < 0.05) lowered the serum levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides (TG), compared with the diabetic positive control (PC) rats. The observed hypoglycemic and hypolipidemic effects of cinnamon extracts in diabetic rats were associated with significant improvements in body weight gain, FI and FER. While, after the 15-day wash-out period, the level of FBG, TC, LDL and TG gradually increased, they were still lower than that in the diabetic PC group of rats. It can be concluded that cinnamon extract exhibits a modulatory role of glycemic and lipidimic profiles in diabetic rats.