Κυριακή, 14 Αυγούστου 2016


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In vitro Antileishmanial and Antimalarial Activity of Selected Plants of Nepal

Source: Journal of Intercultural Ethnopharmacology
Bishnu Joshi, Sarah Hendrickx, Lila Magar, Niranjan Parajuli, Pierre Dorny, Louis Maes.
Ethnopharmacological relevance: Nepal is rich in biodiversity and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases. The aim of this study was to evaluate the in vitro antileishmanial and antimalarial activity of crude methanolic or ethanolic extracts of 30 selected plant species. Materials and methods: Crude extracts of leaves, twigs, aerial parts and/or roots were evaluated for in vitro inhibitory activity against intracellular amastigotes of Leishmania infantum and against erythrocytic stages of Plasmodium falciparum. To determine the selectivity index (SI), cytotoxicity was assessed on MRC5 cells in parallel. Results: Three plant species revealed antiprotozoal activity, namely Phragmites vallatoria, Ampelocissus tomentosa for which no antiprotozoal activity has previously been reported, and Terminalia chebula. The extract of A. tomentosa exhibited moderate activity against L. infantum with an IC50 of 13.2 ± 4.3 µg/ml and SI >3 while T. chebula exhibited fairly good antiplasmodial activity with IC50 values of 4.5 ± 2.4 µg/ml and SI values >5. Conclusion: In countries like Nepal where the current health system is unable to combat the burden of endemic parasitic diseases, evaluation of local plants as a potential source of drug will help in expanding the treatment options. The extent of untapped resources available in these countries provides an opportunity for future bioprospecting. Keywords: Leishmania, Plasmodium, crude plant extracts, in vitro, Nepal

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In vitro Xanthine Oxidase (XO) and Albumin Denaturation Inhibition Assay of Barringtonia racemosa L. and Total Phenolic Content Analysis for Potential Anti-Inflammatory Use in Gouty Arthritis

Source: Journal of Intercultural Ethnopharmacology
Nurul Izzati Osman, Norrizah Jaafar Sidik, Asmah Awal, Nurul Athirah Mohamad Adam, Nur Inani Rezali.
Aim: The present study was conducted to evaluate the in vitro anti-inflammatory activities and total phenolic content (TPC) of methanolic extracts of infloresence axes, endosperms, leaves and pericarps of Barringtonia racemosa L. Methods: The anti-inflammatory study was carried out by assessing the potential through xanthine oxidase (XO) and albumin denaturation inhibition assays. Meanwhile, the total phenolic content (TPC) in the extracts were assessed by Folin Ciocalteu assay. Results: In the XO inhibition assay, the infloresence axes extract was found to exert the highest inhibition capacity at 0.1% (v/v) with 59.54% ± 0.001 inhibition followed by leaves (58.82% ± 0.001), pericarps (57.99% ± 0.003) and endosperms (57.20% ± 0.003) extracts. Similarly in the albumin denaturation inhibition assay, the infloresence axes extract had shown the greatest inhibition capacity with 70.58% ± 0.004 inhibition followed by endosperms (66.80% ± 0.024), leaves (65.29% ± 0.006) and pericarps extracts (43.33% ± 0.002). Meanwhile, for TPC analysis, leaves extract was found to have the highest phenolic content (53.94 ± 0.000 mg GAE/g DW) followed by infloresence axes (31.54 ± 0.001 mg GAE/g DW), endosperms (22.63 ± 0.001 mg GAE/g DW) and the least was found in pericarps (15.54 ± 0.001 mg GAE/g DW). Conclusion: The results indeed verified the in vitro anti-inflammatory activities of B. racemosa and supported its potential to be used in alleviating gouty arthritis and XO-related diseases.

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Evaluation of the synergistic effect of Allium sativum, Eugenia jambolana, Momordica charantia, Ocimum sanctum and Psidium guajav on hepatic and intestinal drug metabolizing enzymes in rats

Source: Journal of Intercultural Ethnopharmacology
Devendra Kumar, Neerja Trivedi, Rakesh K Dixit.
Aims/Background: Present study investigated the synergistic effect of polyherbal formulations (PHF) of Allium sativum L Eugenia jambolana Lam., Momordica charantia L., Ocimum sanctum Linn and Psidium guajava L. in the inhibition/induction of hepatic and intestinal CYPs and Phase-II conjugated drug metabolizing enzymes. Consumption of these herbal remedy has been extensively documented for diabetes treatment in Auyureda. Methodology: PHF of these five herbs was prepared and different doses were orally administered to Sprague Dawley rats of different groups except control group. Expression of mRNA and activity of drug metabolizing enzymes were examined by RT-PCR and HPLC in isolated liver and intestine microsomes in PHF pretreated rats. Results: Activities of hepatic and intestinal Phase-II enzyme levels increased along with mRNA levels except CYP3A mRNA level. PHF administration increases the activity of hepatic and intestinal UDPGT and GST in response to dose and time; however, activity of hepatic SULT increased at higher doses. Conclusions: CYPs and Phase-II conjugated enzymes levels can be modulated in dose and time dependent manner. Observations suggest that poly herbal formulation might be a possible cause of herb-drug interaction, due to changes in pharmacokinetic of crucial CYPs and Phase-II substrate drug.

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RBM4–Nova1–SRSF6 splicing cascade modulates the development of brown adipocytes

Publication date: Available online 12 August 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Jung-Chun Lin, Yi-Lin Chi, Hui-Yu Peng, Yi-Han Lu
Alternative splicing (AS) is a pivotal mechanism for the expansion of gene diversity, which determines the cellular fate or specification. However, the effect of AS networks on brown adipogenesis has not been comprehensively investigated. In this study, we identified the discriminative splicing profiles of RNA-binding motif protein 4a-knockout (RBM4a−/−) brown adipocytes (BAs) and compared them with those of their wild-type counterparts through deep RNA-sequencing. Among these candidates, RBM4a ablation enhanced the relative level of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1−4) transcripts, which were predominantly generated in embryonic BAs. By contrast, most of the Nova1 transcripts were exon 4-included (Nova1+4) in mature BAs. The Nova1 isoforms exhibited differential effects on repressing the development of BAs. Moreover, overexpression of Nova1 proteins reduced he serine/arginine splicing factor 6 (SRSF6) level by enhancing the generation of intron 2-included (SRSF6+intron 2) transcripts, which are a putative candidate of the AS-coupled nonsense-mediated decay mechanism. Furthermore, we observed the positive effect of SRSF6 on BA development. These results highlight the hierarchical role of RBM4a in an AS cascade that manipulates brown adipogenesis.

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Exposure of ionizing radiation on the mammalian brain: Epidemiological evidence, pathological and molecular effects and prevention strategies

Publication date: Available online 13 August 2016
Source:Mutation Research/Reviews in Mutation Research
Author(s): Daniela Hladik, Soile Tapio
Epidemiological studies on the atomic-bomb survivors, cancer survivors and occupational cohorts provide strong evidence for multifaceted damage to brain after ionizing radiation. Radiation-induced late effects may manifest as brain tumors or cognitive impairment. Decreased neurogenesis and differentiation, alteration in neural structure and synaptic plasticity as well as increased oxidative stress and inflammation are suggested to contribute to adverse effects in the brain. In addition to neural stems cells, several brain-specific mature cell types including endothelial and glial cells are negatively affected by ionizing radiation. Radiation-induced enhancement of endothelial cell apoptosis results in disruption of the vascular system and the blood brain barrier. Activated microglia create inflammatory environment that negatively affects neuronal structures and results in decreased synaptic plasticity. Although the molecular mechanisms involved in radiation-induced brain injury remain elusive, first strategies for prevention and amelioration are being developed. Drug-based prevention and treatment focus mainly on the inhibition of oxidative stress and inflammation. Cell replacement therapy holds great promise as first animal studies using transplantation of neural stem cells to irradiated brain have been successful in restoring memory and cognition deficits. This review summarizes the epidemiological and biological data on radiation-induced brain damage and describes prevention and therapy methods to avoid and ameliorate these adverse effects, respectively.

Graphical abstract


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