Chrysin mitigated obesity by regulating energy intake and expenditure in rats.

BACKGROUND AND AIM: Chrysin is a flavonoid found in plant extracts from Passiflora species, honey and propolis. It has demonstrated anti-adipogenic activity in vitro but there are no studies substantiating the anti-obesity activity of chrysin in vivo. EXPERIMENTAL PROCEDURE: The pancreatic lipase (PL) inhibitory potential of chrysin was determined by preliminary in silico screening and further confirmed by in vitro PL inhibitory assay and oral fat tolerance test (OFTT). The effect of chrysin on acute feed intake and sucrose preference test was determined in normal rats. Obesity was induced by feeding of high fructose diet (HFD) to the rats. The rats were divided into six groups: normal control, HFD control, orlistat and three doses of chrysin (25, 50 and 100 mg/kg body weight). Body weight, body mass index (BMI), abdominal circumference/thoracic circumference (AC/TC) ratio, calorie intake, adiposity index, fecal cholesterol, locomotor activity and histopathology of the adipose tissue of the rats were evaluated. RESULTS: Chrysin showed good affinity to PL with competitive type of inhibition. It significantly reduced serum triglycerides in OFTT. Chrysin also significantly reduced acute feed intake and sucrose preference in rats. Chrysin significantly decreased the body weight, BMI, AC/TC ratio, adiposity index, calorie intake while it significantly increased the fecal cholesterol and locomotor activity of the rats. Chrysin was found to reduce the size of the adipocytes when compared to the HFD control group. CONCLUSION: Thus, chrysin exerted anti-obesity effect by inhibiting PL, reducing sucrose preference, reducing calorie intake and increasing the locomotor activity of rats.

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 Ayurvedic medicine, Punica granatum Linn. is considered as 'a pharmacy unto itself". It has been claimed in traditional 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 satellite group was employed in order to check for reversibility of nephrotoxic effects post discontinuation of gentamicin administration. At the end of the study, all the rats were sacrificed and serum-urine parameters were investigated. Antioxidant enzymes and tumor necrosis factor alpha (TNF-α) levels were determined in the kidney tissues along with histopathological examination of kidneys. RESULTS: Increase in serum creatinine, urea, TNF-α, lipid peroxidation along with fall in the antioxidant enzymes activity and degeneration of tubules, arterioles as revealed by histopathological examination confirmed the manifestation of nephrotoxicity caused due to gentamicin. Simultaneous administration of MPGL and gentamicin protected kidneys against nephrotoxic effects of gentamicin as evidenced from normalization of renal function parameters and amelioration of histopathological changes. CONCLUSION: Data suggests that MPGL attenuated oxidative stress associated renal injury by preserving antioxidant enzymes, reducing lipid peroxidation and inhibiting inflammatory mediators such as TNF-α.

Chrysin ameliorates nonalcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome. It begins with the accumulation of fat in the liver (simple steatosis), which if untreated can progress to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Chrysin is a flavonoid present in bee propolis and many other plants. The objective of this study was to determine if chrysin can ameliorate NAFLD induced by feeding a high fructose diet (HFD) in rats. The rats were divided into five groups: normal control, HFD control, chrysin (25, 50, and 100 mg/kg p.o. body weight). Biochemical estimations were carried out in the serum and liver of rats. The gene expressions of SREBP-1c and PPAR α were determined in the liver. The histopathology of the liver was also studied. Chrysin caused a significant decrease in the serum fasting glucose and improved the insulin resistance, dyslipidemia, and liver enzymes. It caused a significant decrease in the liver weight and hepatic free fatty acids, triglyceride, and cholesterol content. Chrysin exerted antioxidant effects, reduced carbonyl content, advanced glycation end products, collagen, TNF-α, and IL-6 concentrations in the liver. Chrysin significantly reduced the hepatic gene expression of SREBP-1c and increased that of PPAR-α. The histopathology of liver of rats treated with chrysin showed significant decrease in the steatosis, ballooning, and lobular inflammation when compared to the HFD control group. Thus, chrysin demonstrated anti-steatotic, antiglycating, antioxidant, anti-inflammatory, and antifibrotic effects and seems to be a promising molecule for the management of NAFLD.

Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress.

BACKGROUND: Chronic consumption of fructose causes obesity and nonalcoholic fatty liver disease (NAFLD). Currently available therapies have limitations; hence there is a need to screen new molecules. Plumbagin is a naphthoquinone present in the roots of Plumbago species which has hypolipidemic and hepatoprotective activities. METHODS: Rats were divided into five groups: normal control, disease control, orlistat, plumbagin (0.5 mg/kg and 1 mg/kg body weight). The normal control group received standard diet and drinking water while the remaining groups received fructose in drinking water alongwith the standard diet for 16 weeks. Orlistat and plumbagin were administered orally from the 9th week-16th week. The body weight, calorie intake and weights of visceral adipose tissue and liver were determined. Blood glucose, insulin, lipid profile and liver function tests were determined. Antioxidant and inflammatory parameters, lipids and collagen were determined in the liver. Gene expression of SREBP-1c and PPAR-α were determined in the liver. The histopathology of the adipose tissue and liver were also studied. RESULTS: Fructose feeding resulted in a significant increase in the body weight gain, calorie intake, visceral fat, liver weight, blood glucose and insulin and caused dyslipidemia which was mitigated by plumbagin. Plumbagin exerted antioxidant, anti-inflammatory and anti-fibrotic effects in the liver and reduced the hepatic lipids. Plumbagin reduced the gene expression of SREBP-1c and increased that of PPAR-α. Plumbagin reduced the hypertrophy of adipocytes and ameliorated the degenerative changes in the liver. CONCLUSION: Plumbagin thus seems to be a promising molecule for the management of obesity and NAFLD.

Fatal dapsone hypersensitivity syndrome with hypothyroidism and steroid-induced diabetes mellitus.

Dapsone has been part of the World Health Organization multidrug therapy for the treatment of leprosy. While it has been efficacious in the management of leprosy, there are many patients who develop adverse drug reactions to the drug including life-threatening reactions such as dapsone hypersensitivity syndrome (DHS). We report a case of a patient who was prescribed dapsone as part of multidrug therapy for leprosy following which she developed DHS. Her condition worsened after tapering the oral steroids given to manage the DHS, and she was detected to have hypothyroidism. She developed diabetes mellitus and succumbed to septic shock.

A Critical Evaluation of Pharmacogenetic Information in Package Inserts for Selected Drugs Marketed in India and Its Comparison With US FDA-Approved Package Inserts.

Our objective was to compare the pharmacogenetic information provided in the package inserts (PIs) of 7 drugs marketed in the United States and India, namely, abacavir, capecitabine, carbamazepine, clopidogrel, irinotecan, valproic acid, and warfarin. We evaluated the pharmacogenetic information provided in Indian PIs for the highest level where it was included, robustness and completeness, clinical validity, and clinical utility and compared it with corresponding data of US PIs. Pharmacogenetic studies carried out in India were identified using PubMed. Pharmacogenetic information was provided in Indian PIs of all the drugs except irinotecan. It appeared in the same section as in US PIs for abacavir, capecitabine, carbamazepine (HLA-*3101), valproic acid (urea cycle disorders), and warfarin (protein C and protein S), whereas it appeared at lower levels for other drug-gene combinations. The robustness of pharmacogenetic testing was graded convincing for abacavir, adequate for carbamazepine and clopidogrel, and incomplete for the remaining drugs, and only abacavir and clopidogrel PIs provided full details of supporting studies. These details, when provided in the Indian PIs were identical to those in the US PIs. The Indian PIs did not provide data on Indian patients, although published studies are available. Both US and Indian PIs lacked critical information on the clinical validity and utility of pharmacogenetic testing. The pharmacogenetic information should provide country/ethnicity-specific data so that they are useful to clinicians. Where data are not available, the prevalence of genetic variation in the population of a country needs to be determined and should then be translated to the PIs.

Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report.

BACKGROUND & OBJECTIVES: With pioglitazone ban and subsequent revoking in India along with varying regulatory decisions in other countries, it was decided to carry out a systematic review on its safety, efficacy and drug utilization in patients with type 2 diabetes mellitus (T2DM) in India and compare with the data from the European Medicines Agency Assessment Report (EMA-AR). METHODS: Systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching Medline/PubMed, Google Scholar and Science Direct databases using 'pioglitazone AND India AND human' and 'pioglitazone AND India AND human AND patient' and compared with EMA-AR. Spontaneous reports in World Health Organization VigiBase from India were compared with VigiBase data from other countries. RESULTS: Sixty six publications, 26 (efficacy), 32 (drug utilization) and eight (safety), were retrieved. In India, pioglitazone was used at 15-30 mg/day mostly with metformin and sulphonylurea, being prescribed to 26.7 and 8.4 per cent patients in north and south, respectively. The efficacy in clinical trials (CTs) was similar to those in EMA-AR. Incidence of bladder cancer in pioglitazone exposed and non-exposed patients was not significantly different in an Indian retrospective cohort study. There were two cases and a series of eight cases of bladder cancer published but none reported in VigiBase. INTERPRETATION & CONCLUSIONS: In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine.

Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control.

Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats.

OBJECTIVES: This study was undertaken to study the effects of melatonin on metabolic and reproductive aspects of polycystic ovary syndrome (PCOS) in rats. METHODS: PCOS was induced by daily subcutaneous administration of testosterone (20 mg/kg) to 21-day-old female rats for 35 days. Rats were given metformin (500 mg/kg), melatonin (1 mg/kg) or melatonin (2 mg/kg) along with testosterone. One group served as vehicle control. On the 36th day, the animals were euthanised, and anthropometrical, biochemical (glucose, insulin, lipids, testosterone, C reactive protein (CRP)), oral glucose tolerance test, and histopathological evaluation of ovaries, uterus and intraabdominal fat (IAF), were carried out. Daily colpocytological examination was carried out from 14(th) day of study until termination. KEY FINDINGS: Both the doses of melatonin significantly reduced body weight, body mass index, IAF, insulin and CRP. A favourable lipid profile, normal glucose tolerance and a decrease in the percentage of estrus smears were observed. Histopathological examination of ovary, uterus and IAF revealed a decrease in the number of cystic follicles, decrease in neoplastic endometrial glands, and decrease in adipocyte hypertrophy, respectively. The effects observed with melatonin were comparable to that with metformin. CONCLUSION: The study provides evidence of the potential beneficial effects of melatonin in PCOS.

Resveratrol- and melatonin-abated ovariectomy and fructose diet-induced obesity and metabolic alterations in female rats.

OBJECTIVE: This study was designed to investigate the effects of bilateral ovariectomy and fructose diet on obesity-related metabolic parameters in female rats. The potential of resveratrol, alone and in combination with melatonin, to counter ensuing obesity and precipitated metabolic disturbances was explored. METHODS: Eight-week-old female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX) or sham operation and randomly assigned to standard diet (SD) or fructose diet (FD) groups (n = 6 rats per group) as follows: Sham; OVX + FD; OVX + SD; OVX + FD + resveratrol 50 mg/kg/day PO (RESV); OVX + SD + RESV; OVX + FD + melatonin 3 mg/kg/day PO in drinking water (M); OVX + SD + M; OVX + FD + RESV + M; OVX + SD + RESV + M. All treatments were given for 7 weeks. Biochemical, dietary, and anthropometrical parameters were estimated, and abdominal fat pads and the liver were examined for histopathological alterations. RESULTS: Ovariectomy caused an increase in body weight, body mass index, feed efficiency, serum glucose, cholesterol, triglycerides, and free fatty acids, which was further exacerbated by fructose diet. These parameters were significantly decreased by resveratrol, alone and in combination with melatonin. Histopathological examination revealed reduced hypertrophy of adipocytes in adipose tissue and reduced macrophage infiltration in the liver. CONCLUSIONS: Resveratrol/melatonin combination effectively normalizes anthropometrical, biochemical, and histopathological parameters in ovariectomized rats with fructose diet-induced obesity and associated metabolic alterations. The combination should be explored for potential benefits in postmenopausal women.