Anand A. Zanwar

Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenalin induced myocardial necrosis in rats

Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenalin induced myocardial necrosis in rats The objective of the study was to evaluate the cardioprotective activity of flax lignan concentrate (FLC) in isoprenalin (ISO) induced cardiotoxicity in rats. Male Wistar rats (200-230 g) were divided into three groups. Group I: control, Group II: isoprenalin, Group III: FLC (500 mg/kg, p.o.) orally for 8 days and in group II and III isoprenalin 5.25 mg/kg, s.c. on day 9 and 8.5 mg/kg on day 10. On day 10 estimation of marker enzymes in serum and haemodynamic parameters were recorded. Animals were sacrificed, histology of heart was performed. Isoprenalin showed cardiotoxicity, manifested by increased levels of marker enzymes and increased heart rate. FLC treatment reversed these biochemical changes significantly compared with ISO group. The cardiotoxic effect of isoprenalin was less in FLC pretreated animals, which was confirmed in histopathological alterations. Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of FLC in isoprenalin induced cardiotoxicity.

Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis

Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.

Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers

Abstract Context: Acetaminophen (APAP) leads to severe hepatic and renal necrosis and thus causes significant clinical problems. Artemisia pallens Walls ex D.C. (Asteraceae) possesses various pharmacological properties such as antidiabetic, antioxidant, analgesic, and anti-inflammatory activity. Objective: The objective was to evaluate the protective effects of Artemisia pallens methanol extract (APME) in APAP-induced hepatic and nephro-toxicity. Materials and methods: The methanolic extract of aerial parts of Artemisia pallens (APME) was prepared. Toxicity was induced in male Wistar rats (180–220 g) by administration of APAP (700 mg/kg, p.o., 14 d). APME (100, 200, and 400 mg/kg, p.o.) was administered to rats 2 h before APAP oral administration. Various biochemical and molecular parameters along with histopathological aberration were studied in the kidney and liver of rats. Results: Pretreatment with APME (200 and 400 mg/kg, p.o.) significantly (p < 0.01 and p < 0.001) decreased aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, blood urea nitrogen (BUN), and serum creatinine as compared with APAP-treated rat. Decreased level of serum albumin, serum uric acid, and HDL were significantly (p < 0.01 and p < 0.001) restored by APME (200 and 400 mg/kg, p.o.) pre-treatment. Administration of APME (200 and 400 mg/kg, p.o.) significantly (p < 0.01 and p < 0.001) reduced the elevated level of cholesterol, LDL, LDH, triglyceride, and VLDL. It also significantly (p < 0.01 and p < 0.001) restored the altered level of hepatic and renal antioxidant enzymes (superoxide dismutase (SOD) and glutathione (GSH)). The increased level of malondialdehyde (MDA) and nitric oxide (NO) in hepatic as well as renal tissue was significantly (p < 0.01 and p < 0.001) decreased by APME (200 and 400 mg/kg, p.o.) administration. Histological alternation induced by APAP in liver and kidney was also reduced by the APME (200 and 400 mg/kg, p.o.) pre-treatment. Conclusion: It is concluded that the methanol extract of Artemisia pallens alleviates APAP induced in rats toxicity through its antioxidative and anti-inflammatory actions.

Evaluating the anti-inflammatory potential of Tectaria cicutaria L. rhizome extract in vitro as well as in vivo

ETHNOPHARMACOLOGICAL RELEVANCE The rhizome of Tectaria cicutaria has been used in the folklore system of Indian traditional medicine (Ayurveda) for the treatment of various disorders such as rheumatic pain, chest complaints, burns, sprain, poisonous bites, tonsilitis, toothache, gum complaints, cuts and wounds. The present work has for the first time tried to elucidate the anti-inflammatory potential of aqueous extract of Tectaria cicutaria rhizome (TCRaq) in vitro as well as in vivo. MATERIALS AND METHODS Anti-inflammatory potential of TCRaq was analyzed in vivo in carrageenan induced rat paw edema model. Serum antioxidant status in TCRaq-treated as well as untreated control rodents was measured by oxygen radical absorbance capacity (ORAC) assay. In vitro experiments for analyzing the anti-inflammatory potential of TCRaq were performed on murine macrophage cell line, RAW 264.7. Analysis of nitric oxide release in RAW 264.7 cells was done by Griess reaction. RT-PCR and western blotting experiment was performed to analyze the expression of iNOS. Expression of COX-2 and NFκB proteins was evaluated by western blotting. RESULTS TCRaq significantly reduced the paw volume in Sprague-Dawley rats at a dose of 200mg/kg body weight, which was comparable with the standard diclofenac treatment. The rats treated with TCRaq showed a significant increase in the serum antioxidant levels compared to the untreated control animals. TCRaq was able to reduce the nitric oxide (NO) levels in RAW 264.7 cells that had been stimulated with lipopolysaccharide (LPS). This was accompanied by a corresponding decrease in iNOS expression at mRNA and protein level. Interestingly, TCRaq was found to decrease the expression of COX-2 as well as the nuclear translocation of NFκB in RAW 264.7 cells. CONCLUSION Our study signifies the anti-inflammatory potential of Tectaria cicutaria and scientifically validates its traditional use in inflammatory conditions.

In vitro antioxidant and antimicrobial activity cycloart–23–ene–3β,-25–diol (B2) isolated from Pongamia pinnata (L. Pierre)

OBJECTIVE To evaluate the in-vitro antioxidant and antimicrobial activity of cycloart-23-ene-3β, 25-diol (called as B2) isolated from stem bark of Pongamia pinnata. METHODS In vitro antioxidant activity of B2 was determined by methods for determination of DPPH radical scavenging, reducing power, superoxide anion radical scavenging, hydroxyl radical scavenging, hydrogen peroxide scavenging, metal chelating and nitric oxide radical scavenging at the doses of 20, 40, 60, 80 and 100 μg/mL, respectively. β-tocopherol with same concentration was used as a standard antioxidant. In vitro antimicrobial activity of B2 was determined by cup plate method in different concentration range of 10-100 μg/mL. RESULTS The results indicated that dose dependent % reduction against DPPH radical, reducing power, superoxide anion radical scavenging, hydroxyl radical scavenging, metal chelating, hydrogen peroxide scavenging and nitric oxide radical scavenging by B2 and β-tocopherol. CONCLUSIONS It is concluded that cycloart 23-ene-3β, 25 diol (B2) showed dose dependent antioxidant activity. B2 showed more DPPH radical scavenging, reducing power, superoxide scavenging, hydroxyl radical scavenging, metal chelating scavenging, hydrogen peroxide radical scavenging and nitric oxide radical scavenging activity than β-tocopherol and in case of antimicrobial activity B2 exhibited broad-spectrum activity against bacteria and strong activity against yeast type of fungi.

L-Glutamine Supplementation Prevents the Development of Experimental Diabetic Cardiomyopathy in Streptozotocin-Nicotinamide Induced Diabetic Rats

The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Abstract Context: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential. Objective: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots. Materials and methods: Hepatotoxicity was induced by oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis. Results: In WRF-treated group, there was significant and dose-dependent (p < 0.01 and p < 0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p < 0.01 and p < 0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p < 0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p < 0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment. Conclusion: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.

Antioxidant Role of Catechin in Health and Disease

Catechin is present in many dietary products, plants, fruits (such as apples, blueberries, gooseberries, grape seeds, kiwi, strawberries), green tea, red wine, beer, cacao liquor, chocolate, cocoa, etc. Tea and red wine are some of the most popular beverages in the world. The antioxidant action of catechin is well-established by various in vitro, in vivo and physical methods. Catechin affects the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, the regulation of cell death, and multidrug resistance in cancers and related disorders. A positive correlation between green tea consumption and cardiovascular health due to several actions such as antioxidative, antihypertensive, anti-inflammatory, antiproliferative, antithrombogenic, and anti-hyperlipidemic etc., is well established based upon epidemiological and experimental studies. Clinical studies have shown the beneficial effects of catechin due its antioxidant action.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl 4 -induced liver damage in rats

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses.

Effect of concomitant administration of L-glutamine and cycloart-23-ene-3β, 25-diol (B2) with sitagliptin in GLP-1 (7-36) amide secretion, biochemical and oxidative stress in streptozotocin - nicotinamide induced diabetic Sprague Dawley rats.

Previously we have reported that, cycloart-23-ene-3β, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7–36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7–36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8th week treatment. Concomitant administration of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7–36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic β cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.