Punica granatum improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress

Background: Gentamicin is widely used as an antibiotic for the treatment of gram negative infections.Evidences indicates that oxidative stress is involved in gentamicin-induced nephrotoxicity. In Ayurvedicmedicine, Punica granatum Linn. is considered as 'a pharmacy unto itself”. It has been claimed intraditional literature, to treat various kidney ailments due to its antioxidant potential.Objective: To explore the possible mechanism of action of methanolic extract of P. granatum leaves(MPGL) in exerting a protective effect on gentamicin-induced nephropathy.Material and methods: Animals were administered with gentamicin (80 mg/kg/day i.m.) and simultaneously with MPGL (100, 200 and 400 mg/kg p.o.) or metformin (100 mg/kg p.o.) for 8 days. A satellitegroup was employed in order to check for reversibility of nephrotoxic effects post discontinuation ofgentamicin administration. At the end of the study, all the rats were sacrificed and serumeurine parameters were investigated. Antioxidant enzymes and tumor necrosis factor alpha (TNF-a) levels weredetermined in the kidney tissues along with histopathological examination of kidneys.Results: Increase in serum creatinine, urea, TNF-a, lipid peroxidation along with fall in the antioxidantenzymes activity and degeneration of tubules, arterioles as revealed by histopathological examinationconfirmed the manifestation of nephrotoxicity caused due to gentamicin. Simultaneous administration ofMPGL and gentamicin protected kidneys against nephrotoxic effects of gentamicin as evidenced fromnormalization of renal function parameters and amelioration of histopathological changes.Conclusion: Data suggests that MPGL attenuated oxidative stress associated renal injury by preservingantioxidant enzymes, reducing lipid peroxidation and inhibiting inflammatory mediators such as TNF-a.© 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Effect of Alstonia scholaris (Linn.) R. Br. on stress and cognition in mice.

Effect of stress and its modulation by methanolic extract of bark of Alstonia scholaris was studied using acute restraint stress model in mice. The extract was also evaluated for nootropic and antioxidant potential to support anti-stress activity testing. Acute restraint stress resulted in significant increase of plasma corticosterone, glucose, protein, cholesterol and triglyceride levels in stress group of animals. Methanolic extract pretreatment at 100, 250 and 500 mg/kg for 7 days displayed promising anti-stress effect by normalizing these stress-induced biochemical perturbations in plasma of mice. Effect on cognitive functions was evaluated using passive avoidance model and elevated plus maze model. Pretreatment with extract at 100, 250 and 500 mg/kg augmented acquisition and retention of memory of learned task as evidenced by increased step-down and shortened-transfer latency in passive avoidance model and elevated plus maze model, respectively. Diazepam (2 mg/kg, ip) and piracetam (200 mg/kg, po) were used as standard drugs for anti-stress and nootropic activity testing. Further, the extract at 200 microg/ml showed maximum scavenging of stable radical 1,1-diphenyl, 2-picryl hydrazyl at 90.11% and nitric oxide radical at 62.77%. The present study, thus, provided scientific support for anti-stress (adaptogenic), antioxidant and nootropic activities of methanolic extract of bark of Alstonia scholaris.

Immunomodulatory activity of methanolic extract of Murraya koenigii (L) Spreng. leaves.

Immunomodulatory activity of methanolic extract of M. koenigii leaves was evaluated on humoral and cell mediated immune response to ovalbumin, phagocytic activity by carbon clearance test, nitric oxide (NO) release from murine peritoneal macrophages and cyclophosphamide induced myelosuppression. Significant increase in the NO production by mouse peritoneal macrophages was detected in culture supernatants indicated increased phagocytic activity of macrophages. The extract showed significant increase in phagocytic index by rapid removal of carbon particles from blood stream. The extract also increased the antibody titre against the ovalbumin and protection towards the cyclophosphamide induced myelosuppression. However, the extract did not show any significant increase in delayed type hypersensitivity reaction which indicated the inability of the extract to stimulate T cells. Present study thus reveals that the extract holds promise as immunomodulatory agent, which acts by stimulating humoral immunity and phagocytic function.

Protective effect of Piper longum L. on oxidative stress induced injury and cellular abnormality in adriamycin induced cardiotoxicity in rats.

Effect of methanolic extract of fruits of P. longum (PLM) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in adriamycin (ADR) induced cardiotoxicity in Wistar rats was investigated. PLM was administered to Wistar albino rats in two different doses, by gastric gavage (250 mg/kg and 500 mg/kg) for 21 days followed by ip ADR (15 mg/kg) on 21st day. ADR administration showed significant decrease in the activities of marker enzymes aspartate transaminase, alanine transaminase, lactate dehydrogenase and creatine kinase in heart with a concomitant increase in their activities in serum. A significant increase in lipid peroxide levels in heart of ADR treated rats was also observed. Pretreatment with PLM ameliorated the effect of ADR on lipid peroxide formation and restored activities of marker enzymes. Activities of myocardial antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase along with reduced glutathione were significantly lowered due to cardiotoxicity in rats administered with ADR. PLM pretreatment augmented these endogenous antioxidants. Histopathological studies of heart revealed degenerative changes and cellular infiltrations in rats administered with ADR and pretreatment with PLM reduced the intensity of such lesions. The results indicate that PLM administration offers significant protection against ADR induced oxidative stress and reduces the cardiotoxicity by virtue of its antioxidant activity.

Antioxidant and anti-inflammatory activity of extract obtained from Aspergillus candidus MTCC 2202 broth filtrate.

Antioxidant potential of Aspergillus candidus MTCC 2202 broth filtrate extract was studied using different antioxidant models, whereas anti-inflammatory potential was studied using carrageenan-induced rat paw oedema model. The ethyl acetate extract at 1000 microg/ml showed maximum scavenging activity of the stable radical 1,1-diphenyl,2-picryl hydrazyl upto 96.65% (IC50=430.36 microg/ml) and scavenging of the radical cation, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) upto 92.25% (IC50=606.29 microg/ml) at the same concentration. The extract had good reducing power, however showed moderate inhibition for conjugated dienes and thiobarbituric acid reactive acid substances (59.56 and 51.45%). The total phenolic content of various extracts of A. candidus broth filtrate was measured and a correlation between radical scavenging activities of extracts with total phenolic content was observed. The ethyl acetate extract (125 mg/kg ip) showed significant anti-inflammatory activity in carrageenan-induced rat paw oedema model. The exhibited antioxidant activity of ethyl acetate extract of A. candidus broth filtrate was comparable with BHA and ascorbic acid, while anti-inflammatory activity was comparable with standard diclofenac sodium.

Positive inotropic effect of Murraya koenigii (Linn.) Spreng extract on an isolated perfused frog heart.

Ethanolic extract of fresh leaves of M. koenigii (MKEE) showed a dose dependent positive inotropic effect on isolated frog heart. The responses to MKEE (62.5-1000 microg) were not affected in either way by theophylline, imidazole, propranolol and sildenafil. The change in potassium and sodium concentration did not alter MKEE-induced positive inotropic effect. Lignocaine did not alter the responses to MKEE significantly. Responses to MKEE were significantly inhibited when calcium concentration was reduced to half (from 1.58 to 0.79 mM) and were significantly potentiated when calcium concentration was doubled (from 1.58 to 3.16 mM). Verapamil was found to inhibit the responses significantly. The results suggest that M. koenigii induced positive inotropic effect possibly by increasing availability of calcium from extra cellular sites.