Target validation and structure-based virtual screening to Discover potential lead molecules against the oncogenic NSD1 histone methyltransferase.

The aim of the study was to validate Nuclear receptor-binding SET Domain NSD1 as a cancer drug target followed by the design of lead molecules against NSD1. TCGA clinical data, molecular expression techniques were used to validate the target and structure-based virtual screening was performed to design hits against NSD1. Clinical data analysis suggests the role of NSD1 in metastasis, prognosis and influence on overall survival in various malignancies. Furthermore, the mRNA and protein expression profile of NSD1 was evaluated in various cell lines. NSD1 was exploited as a target protein for in silico design of inhibitors using two major databases including ZINC15 and ChemDiv by structure-based virtual screening approach. Virtual screening was performed using the pharmacophore hypothesis designed with a protein complex S-adenosyl-l-methionine (SAM) as an endogenous ligand. Subsequently, a combined score was used to distinguish the top 10 compounds from the docking screened compounds having high performance in all four scores (docking score, XP, Gscore, PhaseScreenScore, and MMGBSA delta G Bind). Finally, the top three Zinc compounds were subjected to molecular dynamic simulation. The binding MMGBSA data suggests that ZINC000257261703 and ZINC000012405780 can be taken for in vitro and in vivo studies as they have lesser MMGBSA energy towards the cofactor binding site of NSD1 than the sinefungin. Our data validates NSD1 as a cancer drug target and provides promising structures that can be utilized for further lead optimization and rational drug design to open new gateways in the field of cancer therapeutics. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00158-0.

Selenium-Enriched Probiotic Alleviates Western Diet-Induced Non-alcoholic Fatty Liver Disease in Rats via Modulation of Autophagy Through AMPK/SIRT-1 Pathway.

Current study was aimed to investigate the ability of L.acidophilus SNZ 86 to biotransform inorganic selenium to a more active organic form, resulting in trace element enrichment. Selenium-enriched L. acidophilus SNZ 86 has been shown to be effective in the treatment of a variety of gastrointestinal illnesses, indicating the need for additional research to determine the full potential of this therapeutic strategy in the treatment of metabolic disorders. Herein, we employed the western style diet-induced model of non-alcoholic fatty liver disease (NAFLD) to explore the therapeutic effect of selenium-enriched probiotic (SP). Male Sprague Dawley rats (160-180 g) were fed a high-fat (58% Kcal of fat) and high-fructose (30% w/v) diet for 12 weeks to develop an animal model mimicking NAFLD. High-fat and High-fructose diet-fed rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, abnormal liver function test, increased hepatic oxidative stress, and steatosis. SP was then administered orally (L acidophilus 1 × 109 CFU/ml containing 0.4 g Se/day; p.o.) for 8 weeks. The selenium enrichment within L. acidophilus SNZ 86 was validated by TEM, which allowed for visualisation of the selenium deposition and size distribution in the probiotic. In NAFLD control rats, the expression of autophagy proteins (LC-3 A/B and Beclin), AMPK, and SIRT-1 was significantly reduced indicating downregulation of autophagy. However, supplementation of SP ameliorates hepatic steatosis as evidenced by improved biochemical markers and autophagic activation via upregulation of the AMPK and SIRT-1 pathway showing the relevance of autophagy in the disease aetiology. Collectively, these findings provide us with a better understanding of the role of SP in the treatment of hepatic steatosis and establish a therapeutic basis for potential clinical application of SP in the prevention of NAFLD and associated pathological conditions.

Lactobacillus rhamnosus supplementation ameliorates high fat diet-induced epigenetic alterations and prevents its intergenerational inheritance.

AIM: Multiple studies have reported the epigenetic inheritance of parental metabolic traits could increase the risk of developing metabolic disorders in offsprings. L. rhamnosus (LR) as a probiotic has been found to be beneficial in metabolic diseases. Current study was aimed to explore the effects of LR on high-fat diet induced epigenetic alterations and their transgenerational inheritance. METHODS: Prediabetes was induced in SD rats by feeding HFD for 16 weeks, followed by LR supplementation for 12 weeks, and were put on mating. Biochemical parameters and histopathological changes were assessed in both F0 and F1 generations. Epigenetic alterations were assessed in liver and paternal sperms using Western blotting and qRT-PCR. RESULTS: HFD fed animals displayed alterations in metabolic indices and histopathological features in liver and pancreas which were more prominent in males. These alterations were also inherited to male offsprings. LR supplementation reversed these metabolic and histological alterations in F0 animals and also prevented their intergenerational inheritance. At molecular level, LR supplementation reversed the alterations in miRNA (miR-155-5p, miR-26a-5p, miR-21-5p, miR-200c-3p, and miR-let7a-5p) expression, DNMT1 expression and the histone modification landscape within liver involving H3K36me2, H3K79me2 and H3K27me3 histone marks. Furthermore, expression of the mentioned miRNAs was found to be altered in the sperms of F0 males which was partly restored by LR supplementation. SIGNIFICANCE: Present study indicates that parental HFD-induced prediabetes can transfer the altered epigenetic memory to offspring. Parental LR supplementation can erase this memory and protect the offspring from intergenerational transfer of pathological traits.

High dose nanocrystalline solid dispersion powder of voriconazole for inhalation.

In the current work, we aimed to deliver high dose of voriconazole (VRC) to lung through dry powder for inhalation (DPIs). Furthermore, the research tested the hypothesis that drug nanocrystals can escape the clearance mechanisms in lung by virtue of their size and rapid dissolution. High dose nanocrystalline solid dispersion (NCSD) based DPI of VRC was prepared using a novel spray drying process. Mannitol (MAN) and soya lecithin (LEC) were used as crystallization inducer and stabilizer, respectively. The powders were characterized for physicochemical and aerodynamic properties. Chemical interactions contributing to generation and stabilization of VRC nanocrystals in the matrix of MAN were established using computational studies. Performance of NCSD (VRC-N) was compared with microcrystalline solid dispersion (VRC-M) in terms of dissolution, uptake in A549 and RAW 264.7 cells. Plasma and lung distribution of VRC-N and VRC-M in Balb/c mice upon insufflation was compared with the intravenous product. In VRC-N, drug nanocrystals of size 645.86 ± 56.90 nm were successfully produced at VRC loading of 45%. MAN created physical barrier to crystal growth by interacting with N- of triazole and F- of pyrimidine ring of VRC. An increase in drug loading to 60% produced VRC crystals of size 4800 ± 200 nm (VRC-M). The optimized powders were crystalline and showed deposition at stage 2 and 3 in NGI. In comparison to VRC-M, more than 80% of VRC-N dissolved rapidly in around 5-10 mins, therefore, showed higher and lower drug uptake into A549 and RAW 264.7 cells, respectively. In contrast to intravenous product, insufflation of VRC-N and VRC-M led to higher drug concentrations in lung in comparison to plasma. VRC-N showed higher lung AUC0-24 due to escape of macrophage clearance.

Selenium nanoparticles stimulate osteoblast differentiation via BMP-2/MAPKs/ß-catenin pathway in diabetic osteoporosis.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague-Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results:In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, and promoting calcium nodule formation and collagen content. The authors also provide evidence regarding the involvement of the BMP-2/MAPKs/ß-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, this study provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.

Osteoporosis is a common complication for people with diabetes. High glucose causes oxidative stress, and the antioxidant and anti-inflammatory properties of selenium nanoparticles (SeNPs) make them useful in the treatment of metabolic disorders associated with high glucose levels. The results of this paper report the protective effects of SeNPs in diabetic osteoporosis using rat osteoblastic UMR-106 cells and female Sprague­Dawley rats with type-2 diabetes-induced osteoporosis. SeNPs promote osteoblast differentiation and mineralization in osteoblasts, preserve bone microstructure and improve biomechanical stability, which suggests that SeNPs could be used therapeutically in the maintenance of diabetic osteoporosis.

L-Methionine supplementation attenuates high-fat fructose diet-induced non-alcoholic steatohepatitis by modulating lipid metabolism, fibrosis, and inflammation in rats.

Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied. We, therefore, hypothesized that L-methionine supplementation would ameliorate the progression of hepatic injury in a diet-induced non-alcoholic steatohepatitis (NASH) model and aimed to investigate the underlying mechanism. NASH was developed in male Sprague Dawley rats by feeding them with a high-fat-fructose diet (HFFrD) for 10 weeks. The results demonstrated that L-methionine supplementation to NASH rats for 16 weeks improved the glycemic, lipid, and liver function profiles in NASH rats. Histological analysis of liver tissue revealed a remarkable improvement in the three classical lesions of NASH: steatosis, inflammation, and ballooning. Besides, L-methionine supplementation ameliorated the HFFrD-induced enhanced lipogenesis and lipid peroxidation. An anti-inflammatory effect of L-methionine was also observed through the inhibition of the release of proinflammatory cytokines. Furthermore, the hepatic SIRT1/AMPK signaling pathway was associated with the beneficial effects of L-methionine. This study demonstrates that L-methionine supplementation in HFFrD-fed rats improves their liver pathology via regulation of lipogenesis, inflammation, and the SIRT1/AMPK pathway, thus encouraging its clinical evaluation for the treatment of NASH.

Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats.

BACKGROUND AND AIM: The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. METHODS: The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. RESULTS AND CONCLUSIONS: Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94-44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture.KEY MESSAGESEthanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans.Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases.Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.

Unveiling the presence of epigenetic mark by Lactobacillus supplementation in high-fat diet-induced metabolic disorder in Sprague-Dawley rats.

Gut dysbiosis, particularly bacteria from Firmicutes and Bacteroidetes phyla, plays a fundamental role in the progression of metabolic disorders. Probiotics have shown to restore the gut microbiota composition in metabolic disorders with subsequent beneficial effects. Recent studies have reported that several species of Lactobacillus as probiotic supplementation improve insulin sensitivity and glucose metabolism. Nonetheless, whether Lactobacillus could influence the epigenetic modifications that underlie insulin-resistant conditions is still unexplored. Therefore, the current study examined the therapeutic effects and underlying epigenetic mechanisms of three different species of Lactobacillus in the high-fat diet (HFD)-induced insulin-resistant rats. Three different species of Lactobacillus; Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus rhamnosus were individually supplemented orally (109 CFU/mL) to insulin-resistant SD rats for 12 weeks. Lactobacillus supplementation led to a significant reduction in the hyperglycemia, hyperinsulinemia, and hyperlipidemia associated with HFD-induced insulin resistance. Histopathological examination also indicated the protective effects of Lactobacillus supplementation against the hepatic and intestinal damage caused by the high-fat diet. Lactobacillus supplementation also down-regulated the expression of FOXO1, a major transcription factor of insulin signaling. In addition, at the epigenetic level, Lactobacillus supplementation predominantly prevented methylation and demethylation of H3K79me2 and H3K27me3, respectively. Chromatin Immunoprecipitation (ChIP) coupled with quantitative PCR (ChIP-qPCR) assay revealed the presence of cross-talk between these two histone modifications at the promoter region of FOXO1. Taken together, this is the first report to observe that the effects of Lactobacillus supplementation involve alteration in FOXO1 expression via cross-talking between H3K79me2 and H3K27me3 histone modifications.

Prophylactic Vitamin D Supplementation Practices for Infants: A Survey of Pediatricians From Delhi.

This survey was conducted among 125 pediatricians working in public and private child care facilities of Delhi. Prescription rates of routine vitamin D supplementation varied between 70-100% for various groups of infants, despite non-availability of government guidelines. Pediatricians in private practice more frequently prescribed vitamin D supplementation to term healthy infants as compared to government pediatrician (91.4% vs 71.6%; P=0.005).

Unhealthy Snack Food and Beverage Consumption Is Associated with Lower Dietary Adequacy and Length-for-Age z-Scores among 12-23-Month-Olds in Kathmandu Valley, Nepal.

BACKGROUND: Consumption of unhealthy snack foods and beverages (USFBs) in low- and middle-income countries (LMICs) is rising, with global awareness increasing about risks of overnutrition. However, little is known about the relation between USFB consumption and young children's diet/nutritional outcomes in contexts where nutrient density of complementary foods is often low. OBJECTIVES: This study assessed the association of high USFB consumption, compared with low consumption, with nutrient intakes, dietary adequacy, iron status, and growth in young children in Kathmandu Valley, Nepal. METHODS: A cross-sectional survey was conducted in a representative sample of 745 primary caregivers of children aged 12-23 mo. Food consumption was measured through quantitative 24-h recalls, and child anthropometric measurements and capillary blood samples were collected. Using adjusted linear/logistic regression models, nutrient intakes, dietary adequacy, length-for-age and weight-for-length z-scores (LAZ and WLZ, respectively), and iron status were compared between lowest and highest tertiles of consumption based on the contribution of USFBs to total energy intakes (TEIs). Mediation of the relation between USFB consumption and LAZ via lowered dietary adequacy was explored using structural equations modeling. RESULTS: On average, USFBs contributed 46.9% of TEI among the highest tertile of consumers, compared with 5.2% of TEI among the lowest. Compared with low-USFB consumers, high-USFB consumers had lower nutrient intakes and a greater proportion were at risk of inadequate intakes for 8 nutrients. Mean LAZ was nearly 0.3 SD lower among high-USFB consumers than low consumers (P = 0.003), with this relationship partially mediated through dietary adequacy. No associations were found with stunting prevalence or iron status. Prevalence of overweight/obesity was low. CONCLUSIONS: In this LMIC context, high USFB consumption among young children was associated with inadequate micronutrient intakes, which can contribute to poor growth outcomes. Addressing increased availability of USFBs in LMIC food systems should be a priority for policies and programs aiming to safeguard child nutrition.

HUMAN KIDNEY AND SKELETON URANIUM BURDEN, RADIATION DOSE AND HEALTH RISKS FROM HIGH URANIUM CONTENTS IN DRINKING WATER OF BATHINDA DISTRICT (MALWA REGION) OF PUNJAB STATE, INDIA.

Uranium concentration has been measured in drinking water samples from the Bathinda district. It ranges from 2.4 to 529 µg/l with a mean value of 120 µg/l. The mean uranium kidney burden for children and adults is 0.0838 and 0.059 µg U/g, respectively, which crosses the safe limit of 0.02 µg U/g. The mean values for skeleton burden are 1925.7 µg for children and 4108.2 µg for an adult. These values are 32 and 69 times higher than the skeleton burden of 59.4 µg for a normal adult. Radiological and chemical risk is also found to be higher than the recommended values. The mean effective ingestion dose for different age groups and genders is 188.2 µSv/y, while the safety limit is 100 µSv/y. The dose to the kidney, bone surface and bone marrow has also been evaluated. The observed values of the studied parameters show that people of this area may be at higher health risks corresponding to the intake of water; children may be the most affected.

Vitamin D Supplementation for Treatment and Prevention of Pneumonia in Under-five Children: A Randomized Double-blind Placebo Controlled Trial.

OBJECTIVE: To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in under-five children. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: Tertiary-care hospital. PARTICIPANTS: 324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL). INTERVENTION: 100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment. Outcome variables: Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness. OUTCOME VARIABLES: Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness. RESULTS: Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1.39 (1.11, 1.76); P = 0.005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22.8%); vitamin D: 39/156 (25%); RR (95% CI): 1.13 (0.67,1.90); P 0.69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention. CONCLUSION: There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.

Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells.

BACKGROUND: The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells. HYPOTHESIS: This study was designed systematically to explore Xylaria psidii, an endophytic fungus for the identification of biologically active secondary metabolites against pancreatic cancer cells. METHODS: While exploring the bioactive secondary metabolites, a sensitive and reliable LC-MS based dereplication approach was applied to identify four compounds A-D from fungal extract. Further bioactivity guided isolation of fungal extract yielded two major metabolites 1 and 2. The structures of 1 and 2 have been determined by detailed spectroscopic analysis including MS, NMR, IR and UV data and similarity with published data. Xylarione A (1) is new whereas (-) 5-methylmellein (2) is reported for the first time from X. psidii. Both the isolated compounds were screened for their effect on the viability and proliferation against a panel of cancer cell lines (MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2 and DU145) of different tissue origin. RESULTS: Compounds 1 and 2 exhibited cytotoxicity against pancreatic cancer (MIA-Pa-Ca-2) cells with IC50 values of 16.0 and 19.0 µm, respectively. The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Cell death induced by 1 and 2 displayed features characteristic of apoptosis. Flow cytometry based analysis of 1 and 2 using Rhodamine-123 displayed substantial loss of mitochondrial membrane potential in a concentration dependent manner by both the compounds. CONCLUSION: Results conclude that the isolated compounds 1 and 2 are responsible for the activity shown by crude ethyl acetate extract and may act as potential leads for medicinal chemists for designing more potent analogs.

Therapeutic hypoglycemic potential of Pentapetes phoenicea L. in experimentally induced hyperglycemic rats.

Diabetes mellitus is a metabolic disorder of endocrine system. This dreadful disease is found all over the world and is becoming a serious threat to the mankind health. Alternative to synthetic agents, plants provide a potential source of hypoglycemic drugs. The aim of the present study was to evaluate the hypoglycemic effect of 70% alcoholic extract of Pentapetesphoenicea (PPE) on blood glucose level in glucose loaded, normal and experimentally induced diabetic rats. Based on the acute toxicity test, two variable doses (250, 500 mg kg(-1) b.wt.) of hydro-alcoholic extract of P. phoenicea leaves were compared with glibenclamide for the influence on fasting blood glucose in glucose loaded, normoglycemic and streptozotocin (STZ) (55 mg kg(-1), i.p.) induced hyperglycemic rats. All the statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Newman-Keuls Multiple Comparison Test using Graph Pad Prism 4.01 v for windows (Graph Pad Software, San Diego, CA, USA). The difference showing a p level of 0.05 or lower was considered to be statistically significant. The administration of PPE in two doses and glibenclamide (5 mg kg(-1)) to STZ induced hyperglycemic animals significantly lowered the blood glucose levels with 18.84% (p<0.01) for PPE 250 mg kg and 38.89% (p<0.001) for PPE 500 mg kg(-1) in a dose dependant manner. Considering all the results obtained, the study concludes that the hydro-alcoholic extract of P. phoenicea leaves produced promising decrease in blood glucose levels in STZ induced hyperglycemic rats which might be related to tannins, terpenoids, sterols and flavonoid contents.

Protective effect of standardized extract of Cleome viscosa against experimentally induced gastric lesions in the rat.

CONTEXT: Cleome viscosa Linn. (Capparidaceae) is used traditionally in the Indian system of medicine as a carminative, anthelmintic, and diuretic, and used for healing wounds, ulcers and diarrhea. OBJECTIVE: A 70% ethanol (EtOH) extract of the aerial parts of Cleome viscosa extract (CVE) was investigated for gastroprotective activity in different gastric ulcer models in order to validate ethnobotanical claims regarding the plant use in ulcers. MATERIALS AND METHODS: CVE (100, 200 and 400 mg/kg body weight) was administered orally, twice daily for 5 d, for prevention from EtOH, pylorus ligation (PL) and cold restraint stress (CRS)-induced ulcers in rats. Estimation of H(+)K(+)ATPase activity and gastric wall mucous were performed in EtOH-induced ulcer, antioxidant enzyme activities in supernatant mitochondrial fraction of CRS-induced ulcer, and gastric secretion parameters were estimated in PL-induced ulcer model. RESULTS: CVE showed significant (p < 0.01) dose-dependent inhibition of lesion index in EtOH 15.93-42.30%, PL 26.34-59.28% and CRS 22.58-54.03%, respectively. CVE prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by a significant (p < 0.001) decrease in superoxide dismutase, and an increase in catalase activity. A significant (p < 0.01) decrease occurred in the level of H(+)K(+)ATPase, volume of gastric juice and total acidity. Simultaneously, the level of gastric wall mucus and pH were increased significantly (p < 0.05). High performance thin layer chromatography analysis showed the presence of quercetin and gallic acid (0.3% and 0.25% w/w, respectively) in CVE. CONCLUSIONS: Results of our study showed that C. viscosa possesses significant gastroprotective activity, probably due to free radical scavenging activity, and validates the folklore claim.

A review on ethnobotany, phytochemistry and pharmacology of Fumaria indica (Fumitory).

Fumaria indica (Hausskn.) Pugsley (Fumariaceae), known as "Fumitory", is an annual herb found as a common weed all over the plains of India and Pakistan. The whole plant is widely used in traditional and folkloric systems of medicine. In traditional systems of medicine, the plant is reputed for its anthelmintic, diuretic, diaphoretic, laxative, cholagogue, stomachic and sedative activities and is used to purify blood and in liver obstruction in ethnopharmacology. The whole plant is ascribed to possess medicinal virtues in Ayurvedic and Unani systems of medicine and is also used in preparation of important Ayurvedic medicinal preparations and polyherbal liver formulations. The review reveals that phytochemical constituents of wide range have been separated from the plants and it possesses important pharmacological activities like smooth muscle relaxant, spasmogenic and spasmolytic, analgesic, anti-inflammatory, neuropharmacological and antibacterial activities. The separation of hepatoprotective and antifungal constituents from this plant was also reported newly. This review highlights the traditional, ethnobotanical, phytochemical, pharmacological information available on Fumaria indica, which might be helpful for scientists and researchers to find out new chemical entities responsible for its claimed traditional uses.

Pharmacognostic studies of the leaves and stem of Careya arborea Roxb.

OBJECTIVE: To study detailed pharmacognostic profile of leaves and stem of Careya arborea (C. arborea) Roxb. (Lecthyidaceae), an important medicinal plant in the Indian system of medicine. METHODS: Leaf and stem samples of C. arborea were studied by macroscopical, microscopical, physicochemical, phytochemical, fluorescence analysis of powder of the plant and other methods for standardization recommended by WHO. RESULTS: Macroscopically, the leaves are simple, broadly obovate in shape, acuminate apex with crenate, dentate margin, petioles (0.1-1.8 cm) long. Microscopically, the leaf showed the presence of median large size vascular bundle covered with fibrous bundle sheath, arrangement of xylem in cup shape and presence of cortical vascular bundle, patches of sclerenchyma, phloem fibers in groups and brown pigment containing cells in stem are some of the diagnostic features noted from anatomical study. Powder microscopy of leaf revealed the presence of parenchyma cells, xylem with pitted vessels and epidermis with anisocytic stomata. The investigations also included leaf surface data; quantitative leaf microscopy and fluorescence analysis. Physiochemical parameters such as loss on drying, swelling index, extractive values and ash values were also determined and results showed that total ash of the stem bark was about two times higher than leaf and water soluble extractive value of leaf and stem bark was two times higher than alcohol soluble extractive value. Preliminary phytochemical screening showed the presence of triterpenoids, saponins, tannins and flavonoids. CONCLUSIONS: The results of the study can serve as a valuable source of information and provide suitable standards for identification of this plant material in future investigations and applications.