The fruits of Emblica officinalis (Amla) are widely used in the Indian System of Medicine and are believed to increase defense against disease. In the present study, the effects of chronic oral administration of fresh fruit homogenate of Amla on: (i). myocardial antioxidant system and (ii). oxidative stress induced by ischemic-reperfusion injury (IRI) in rat heart were investigated. Fresh amla fruit homogenate, in three different doses (250, 500 and 750 mg/kg) and normal saline (C) were administered orally to Wistar albino rats (120-150 gms) of either sex daily for 30 days. There was reduction in basal myocardial lipid peroxidation, as evidenced by decreased thiobarbituric acid reactive substances (TBARS) level, and augmentation of myocardial endogenous antioxidants, like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the treated rats. Hearts were also subjected to in vitro IRI (9 min of global ischemia, followed by 12 min of reperfusion, Langendorff's mode). Significant myocyte injury and rise in myocardial TBARS along with depletion of SOD, catalase, GSH (reduced glutathione) and GPx occurred in the control group. No significant increase in myocardial TBARS and depletion of antioxidant enzymes were observed in the treated groups. Myocyte injury was evident only in 250 mg/kg group. The results indicate that chronic Emblica officinalis administration causes myocardial adaptation by augmenting endogenous antioxidants and protects rat hearts from oxidative stress associated with ischemic-reperfusion injury.
The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.
Meloxicam, a non-steroidal anti-inflammatory drug, is a preferential inhibitor of cyclooxygenase-2 and has demonstrated potent analgesic and anti-inflammatory activity after oral administration. The present work was carried out to elucidate the anti-inflammatory and analgesic activity of a newer topical gel formulation of meloxicam (1% w/w gel) and compare it with 0.5% w/w piroxicam and 1% w/w diclofenac gels in experimental animal models. The study was also extended to determine the pharmacokinetic profile of a newer formulation of meloxicam gel after topical application on depilated skin of rats. The anti-inflammatory activities of meloxicam, piroxicam and diclofenac gels were compared using carrageenan-induced acute paw oedema and complete Freund’s adjuvant-induced chronic paw oedema in rats. Meloxicam gel showed increased protection against inflammation as compared to piroxicam and diclofenac gels. Acetic acid-induced writhing and formalin-induced phase I and phase II pain models were used to compare their analgesic activity. Meloxicam gel showed significant protection in formalin-induced phase II pain whereas its analgesic activity was less as compared to diclofenac and piroxicam gels in writhing test and formalin-induced phase I pain. The pharmacokinetic studies showed peak plasma drug concentration (Cmax) of 48.48 ± 6.57 µg/ml at 2 h (Tmax) after topical application of 500 mg of meloxicam gel formulation. The area under the curve as calculated from 0 to 6 h was found to be 114.18 ± 4.23 and 194.13 ± 3.78 µg·h/ml for 0 to ∝. The results indicate that topical preparation of meloxicam could be an effective alternative to diclofenac and piroxicam gels in inflammatory conditions and its associated pain with the possibility of less systemic side-effects.
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