A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism 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 the present study, the long-term effect of 3-HMX in type 2 diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body weight) was orally administered for 45 days to streptozotocin-diabetic rats for the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA(1c)), hepatic glycogen, and activities of carbohydrate metabolizing enzymes, such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters studied as that of glibenclamide, a standard drug. Histological study of pancreas also confirmed the biochemical findings. These results indicate that 3-hydroxymethyl xylitol, the compound from C. esculenta, possesses antihyperglycemic effect on long-term treatment also.     

Ethnobotanical survey of folk plants for the treatment of snakebites in Southern part of Tamilnadu, India

Ethnobotanical surveys were conducted in four different indigenous groups in Southern parts of Tamilnadu, India, using a questionnaire. The herbal practitioners in the study area were interviewed, and information on medicinal plants was collected from the traditional healers called "Vaidyars". This survey covers 72 medicinal plants belonging to 53 families that are used for the treatment of snakebite in a traditional way. Traditional approach was evaluated scientifically with some selected plant extracts (7.2 mg/kg bw) and partially purified fractions (2.4 mg/kg bw) were orally administered to mice experimentally envenomed with rattlesnake venom s.c. injection (2.5-15 microg/kg bw). Tested fractions (Aristolochia indica, Hemidesmus indicus, Gloriosa superba, Strychnos nux-vomica, Eclipta prostrata, and Andrographis paniculata) showed potent neutralizing effect against the venom. Compared to the extracts, administration of purified fractions was more effective in increasing the body weight. Control mice injected with the venom alone showed weight loss and severe toxicity at 15 microg/kg bw. The purified fractions (2.4 mg/kg bw) produced significant protection against venom induced changes in serum SOD and LPx levels. The isolated fractions effectively inhibited the toxic effect of snake venoms in vitro than in vivo. The above observations confirmed the protective activity of plants-Aristolochia indica, Hemidesmus indicus, Gloriosa superba, Strychnos nux-vomica, Eclipta prostrata, and Andrographis paniculata against the lethal action of snake venom and need further investigation.     

Soluble ST2: a valuable prognostic marker in heart failure

Heart Failure Reviews - Natriuretic peptides have been at the forefront of biomarker use in heart disease and have been universally recommended as the ideal biomarker in the setting of heart...     

Gene-environmental interaction in asthma

PURPOSE OF REVIEW: Asthma is likely to result from the effects of environmental stimuli in genetically susceptible individuals. This review summarizes recent studies of gene-environmental interaction in the pathogenesis of asthma, focusing on study designs. RECENT FINDINGS: Studies using genetic epidemiology, in-vitro and ex-vivo models and in-vivo model organisms demonstrate that gene-environmental interaction in involved in the development of asthma. Genetic association studies show a reduced risk of asthma and atopy with early life exposure to farming environments and house dust endotoxin, and increased risk with environmental tobacco smoke. These associations are modified by CD14 genotype. In people with a specific genotype, high environmental exposure may have the opposite effect of low exposure, possibly explaining some of the inconsistencies in previous studies. In-vitro and ex-vivo cell culture experiments show gene-environmental interactions with Toll-like receptor agonists, viruses and tobacco smoke. Interactions between innate immunity genes and exposure to endotoxin and air pollution have been observed in in-vivo mouse models. SUMMARY: The expanding evidence for gene-environmental interaction in asthma indicates the importance of measuring environmental factors in genetic studies of asthma. Understanding gene-environmental interaction would facilitate risk prognostication, improve preventive strategies and develop targeted interventions in people with asthma.     

Cancer Chemopreventive Potential of Luteolin-7-O-Glucoside Isolated From Ophiorrhiza mungos Linn

The anticarcinogenic potential of the phytocompound Luteolin-7-O-Glucoside (LUT7G), isolated from the leaves of Ophiorrhiza mungos Linn, was studied against 4 different cancer cell lines (COLO 320 DM, AGS, MCF-7, and A549) and normal VERO cell line. The ability of LUT7G to induce apoptosis was determined by its antiradical activity, DNA fragmentation, expression of β-catenin, and chemopreventive efficacy in vivo by administering rats with DMH (20 mg/kg b.w., s.c.) for 4 consecutive wk and supplementing with 3 different doses throughout the experimental period of 16 wk. LUT7G scavenged 80% of DPPH radicals generated in vitro at 1000 μM and suppressed the expression of β-catenin to 40% at 120 μM concentrations. LUT7G induced apoptosis by scavenging ROS and suppressing the expression of β-catenin in COLO 320 DM cells and effectively inhibited ACF development in DMH-induced experimental carcinogenesis. Hence LUT7G can be a potent anticancer drug for colon carcinogenesis.     

Nitro-Arginine Methyl Ester,a Non-Selective Inhibitor of Nitric Oxide Synthase Reduces Ibuprofen-Induced Gastric Mucosal Injury in the Rat

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug. Gastrointestinal adverse drug reactions from ibuprofen usage include gastric mucosal ulcers and bleeding. The mechanism by which ibuprofen induces gastric mucosal damage is not clear. The present study is an attempt to examine the role of nitric oxide in the pathogenesis of ibuprofen-induced gastric mucosal damage. Ibuprofen administered orally at the dose of 100 mg/kg body weight for 6 days to the rats resulted in gastric mucosal injury. Serum nitrite and nitrosothiol were increased significantly as compared with the controls, which were treated with the vehicle alone. In the gastric mucosa, lipid peroxidation and protein thiols were increased, and the activity of glyceraldehyde 3-phosphate dehydrogenase, a nitric oxide sensitive enzyme was decreased significantly. Pretreatment of the rats daily with nitric oxide synthase inhibitor, nitro-arginine methyl ester (30 mg/kg body weight) 1 hr before treatment with ibuprofen reduced the gastric mucosal injury. Biochemically, it prevented the rise in serum nitrite levels and the increase in lipid peroxidation and protein thiol levels and the loss of glyceraldehyde 3-phosphate dehydrogenase activity in the gastric mucosa. The results of the present study suggest that increased nitric oxide production may be one of the mechanisms by which ibuprofen produces gastric mucosal injury and that inhibition of nitric oxide synthase reduces gastric mucosal injury.     

In silico molecular docking of niloticin with acetylcholinesterase 1 (AChE1) of <Emphasis Type="Italic">Aedes aegypti</Emphasis> L. (Diptera: Culicidae): a promising molecular target

Synthetic insecticides used in mosquito control program are harmful to environment and also affect other associated organisms. As a choice, plant-based natural compounds proved to be a good alternative to synthetic insecticides. In a study, we had reported niloticin (C₃₀H₄₈O₃) from the plant Limonia acidissima L. was effective and disturbed the larval growth of A. aegypti. The main molecular target for many commercially available synthetic mosquitocides is acetylcholinesterase (AChE), which plays a major role in larval knockdown/resistant mechanisms. AChE1 is a serine protease, which fulfills the physiological function of neurotransmitter hydrolysis at synapses. In the present study, we performed molecular docking studies with acetylcholinesterase 1 (AChE1) of A. aegypti with niloticin (C₃₀H₄₈O₃) and compared with commercially available chemical larvicidal compound temephos (C₁₆H₂₀O₆P₂S₃). The docking results revealed that the binding affinities and energy values of niloticin (?8.4 kcal/mol) were found to be significantly higher than temephos (?4.75 kcal/mol). Both niloticin (C₃₀H₄₈O₃) and temephos (C₁₆H₂₀O₆P₂S₃) showed the same binding residues (THR’58 and HIS’62) on AChE1. Further, niloticin produced least binding energy (?8.4 kcal/mol), good inhibition constant value (695.18 μM) and high ligand efficiency (0.25) than temephos, suggesting that niloticin (C₃₀H₄₈O₃) could be used against the larvae of A. aegypti as an effective AChE1 inhibitor.