Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive compound, arjunolic acid (AA), in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target. Our data revealed that AA significantly represses collagen expression and improves cardiac function during hypertrophy. We found that AA binds to and stabilizes the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) and increases its expression during cardiac hypertrophy. PPARα knockdown during AA treatment in hypertrophy samples, including angiotensin II-treated adult cardiac fibroblasts and renal artery-ligated rat heart, suggests that AA-driven cardioprotection primarily arises from PPARα agonism. Moreover, AA-induced PPARα up-regulation leads to repression of TGF-β signaling, specifically by inhibiting TGF-β-activated kinase1 (TAK1) phosphorylation. We observed that PPARα directly interacts with TAK1, predominantly via PPARα N-terminal transactivation domain (AF-1) thereby masking the TAK1 kinase domain. The AA-induced PPARα-bound TAK1 level thereby shows inverse correlation with the phosphorylation level of TAK1 and subsequent reduction in p38 MAPK and NF-κBp65 activation, ultimately culminating in amelioration of excess collagen synthesis in cardiac hypertrophy. In conclusion, our findings unravel the mechanism of AA action in regressing hypertrophy-associated cardiac fibrosis by assigning a role of AA as a PPARα agonist that inactivates non-canonical TGF-β signaling.
Lignin is a major component of all plants, the degradation of which remains a major challenge to date owing to its recalcitrant nature. Several classes of fungi have been studied to carry out this process to some extent, but overall the process remains inefficient. We have isolated a novel alkalophilic dimorphic lignin-degrading Deuteromycete from soil, identified as “uncultured” and coded as MVI.2011. Supernatant from 12-h culture of MVI.2011 in optimized mineral medium containing lignin pH 9.0 was analysed for Lignin Peroxidase, Manganese Peroxidase and Laccase. Enzyme purification was carried out by standard protocols using ammonium sulphate precipitation followed by further purification by Gel Permeation Chromatography. Analysis of total protein, specific enzyme activity and molecular weight of the GPC-purified LiP, MnP and Laccase showed 93.83 μg/ml, 5.27 U/mg, 42 kDa; 78.13 μg/ml, 13.18 U/mg, 45 kDa and 85.81 μg/ml, 4.77 U/mg, 62 kDa, respectively. The purified enzymes possessed high activity over a wide range of pH (4–11), and temperature (30–55 °C). The optimum substrate concentration was 20 μg/ml of lignin for all the three enzymes. CD spectra suggested that the predominant secondary structure was helix in LiP, and, turns in MnP and Laccase. The breakdown products of lignin degradation by MVI.2011 and the three purified enzymes were detected and identified by FTIR and GC–MS. They were oxalic acid, hentriacontane, derivatives of octadecane, nonane, etc. These vital compounds are certain to find application as biofuels, an alternate energy source in various industries.Electronic supplementary materialThe online version of this article (doi:10.1007/s13205-016-0384-z) contains supplementary material, which is available to authorized users.
Arjunolic acid (AA), a triterpenoid, was isolated from the ethyl acetate and methanol extracts of Terminalia arjuna core wood. The purity of AA was analysed by its melting point, FT-IR and NMR spectroscopy analyses. In vitro cytotoxicity was assessed using Ehrlich ascites carcinoma (EAC) and Dalton's lymphoma (DAL) cell lines by incubating with different concentrations of AA. The cancer cell death percentage at 100 µg concentrations of AA ranged between 66% and 70% on the DAL and EAC cell lines, respectively. This infers that AA causes considerable membrane damage to cancer cells.
plant kingdom has been described as a reservoir of many novel biologically active molecules of medicinal value. [2] Recently there has been a surge of interest in the therapeutic potential of medicinal plants as antioxidants in reducing free radical-induced tissue injury. Alstonia scholaris belongs to the family apocyanaceae which consists of about 250 genera and 2000 species of tropical trees, shrubs and vines. [3] Almost all parts of this plant are used in medicine and the bark has antihelminthic and astringent properties. It has been used in treating chronic diarrhea, dysentery and abnormal bowel movements. [4] The objective of the present study was to screen the phytochemicals and assess the antioxidant activity of the solvent extracts of bark and leaf of Alstonia scholaris. Free radical scavenging ability of the extracts were tested using antioxidant assays, viz., DPPH assay, ABTS assay and FRAP assay. MATERIALS AND METHODS The bark and leaves of Alstonia scholaris were collected from VIT University campus, Vellore and authenticated by Plant Biotechnology division, VIT University, Vellore. The samples were washed thoroughly and dried. The dried samples were pulverized and 100g of the powered samples were refluxed with ethyl acetate, butanol and water in the ratio 1:10(w/v). The extracts were then concentrated using rotary flash
The pigmented, rod-shaped, Gram-negative, motile bacteria isolated from marine sponge Callyspongia diffusa exhibiting bioactivity was characterized as Shewanella algae (GenBank: KC623651). The 16S rRNA gene sequence-based phylogenetic analysis showed its similarity with the member of Shewanella and placed in a separate cluster with the recognized bacteria S. algae (PSB-05 FJ86678) with which it showed 99.0 % sequence similarity. Growth of the strain was optimum at temperature 30°C, pH 8.0 in the presence of 2.0-4.0 % of NaCl. High antibiotic activity against microbes such as Escherichia coli (MTCC 40), S. typhii (MTCC 98), P. vulgaris (MTCC 426), V. fluvialis, V. anguillarum, E. cloacae, and L. lactis was recorded. The growth of fungal pathogens such as Aspergillus niger, Aspergillus fumigatus, Saccharomyces cerevisiae, and Colletotrichum gloeosporioides was effectively controlled.
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