Biochemical responses and antioxidant defense mechanisms in Channa Striatus exposed to Bisphenol S.

Bisphenol S (BPS), a BPA analog and a safer alternative, is utilized in a diverse range of industrial applications, such as making polycarbonate plastics, epoxy resins, thermal receipt papers, and currency bills. Recently, the increased use of BPS in containers and packages for daily life has been interrogated due to its identical chemical structure and probable endocrine-disrupting actions as BPA has. The present study aimed to evaluate the alterations in biochemical indices and antioxidant enzymes as certain indicators of the endocrine-disrupting effect of BPS in Channa striatus, a freshwater fish. BPS-exposed fish species were subjected to three sub-lethal concentrations of BPS (1, 4, and 12 ppm) and observed after an interval of 7 and 21 days. Exposure to BPS caused a reduction in the level of protein in muscle, gonads and the liver due to an impairment of protein synthesis. Levels of cholesterol in the muscle, gonads, and liver of BPS-exposed fish were found to be decreased after treatment, indicating either an inhibition of cholesterol biosynthesis in the liver or reduced absorption of dietary cholesterol. The levels of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase showed remarkable increases, while the activity of glutathione S-transferase decreased considerably, indicating the antioxidant defense mechanism to counteract the oxidative stress induced by BPS. Moreover, a significant increase was noted in the level of lipid peroxidation products, like malondialdehyde and conjugate diene, which represent biomarkers of oxidative stress. The histoarchitecture changes were also observed in the liver, muscle and gonads of BPS-treated fish species. The present study showed that sub-lethal exposure to BPS significantly influenced the activities of these enzymes and peroxidation byproducts. From this study, it is concluded that BPS-caused toxic effects in fish species lead to an imbalance in the antioxidant defense system. It is clearly indicated that BPS toxicity could lead to susceptible oxidative stress in various tissues and could damage vital organs.

Supramolecular Surface Charge Regulation in Ionic Covalent Organic Nanosheets: Reversible Exfoliation and Controlled Bacterial Growth.

Poor control on the exfoliation of covalent organic frameworks (COFs) remains a disadvantage for their application as two-dimensional nanosheets. An equally important problem is the reversible control at the available surface charges on COFs. Herein, a strategy for the reversible exfoliation, re-stacking, and surface-charge control of a propidium iodide based ionic covalent organic framework, PI-TFP, using cucurbit[7]uril (CB[7]) induced molecular recognition, is reported. The surface charge on PI-TFP facilitates its initial self-exfoliation. However, complexation with CB[7] resulted in re-stacking with concomitant decrease in zeta potential from +28±3.0 to +0.004±0.003 mV. Addition of 1-adamantylamine hydrochloride (AD) facilitates decomplexation of PI-TFP from CB[7], resulting in exfoliation and an increase in zeta potential to +24±3.0 mV. Such control on the exfoliation, re-stacking, and the associated regulation of the surface charge in PI-TFP was exploited for controlling bacterial growth. Thus, the activity of E. coli and S. aureus bacteria obtained with the self-exfoliated PI-TFP could be reversibly controlled by the CB[7]/AD pair.

Enhanced antibacterial metabolite production through the application of statistical methodologies by a Streptomyces nogalater NIIST A30 isolated from Western Ghats forest soil.

Streptomyces strains isolated from Nelliyampathy forest soil of Western Ghats, Kerala, India were evaluated for their antibacterial efficacy against two indicator pathogenic bacteria (Escherichia coli and Staphylococcus aureus). Among 140 strains tested, sixteen recorded potent antibacterial properties and were further screened against eleven bacterial pathogens. A strain identified as Streptomyces nogalater and designated as NIIST A30 exhibited maximum inhibition against all the test pathogens. Among the eight fermentation media tested, inorganic salts starch broth recorded the best for antibacterial production. The ethyl acetate crude extract exhibited antioxidant properties with IC50 value of 30 µg/mL and had no cytotoxicity towards L6, H9c2 and RAW 264.7 cell lines up to a concentration of 50 µg/mL. Maximum metabolite production was achieved in pH 7.0 at 35°C after 7 days incubation. The significant media components for maximum metabolite production were optimized through response surface methodology employing Plackett-Burman and Box-Behnken designs. The composition of the final optimized medium was soluble starch, 14.97g; (NH4)2SO4, 2.89g; K2HPO4, 2.07g; MgSO4.7H2O, 1g; NaCl, 1g, CaCO3, 2g; FeSO4.7H2O, 1mg; MnCl2.7H2O, 1mg; and ZnSO4.7H2O, 1mg per litre of distilled water. The optimization resulted an antibacterial activity of 28±1.5mm against S. epidermidis which was in close accordance with the predicted value of 30 mm. It is also evident from the result that an increase of 86.66% antibacterial production was recorded in optimized media. The chosen method was economical, efficient and useful for future antibacterial drug discovery from a broad spectrum metabolite producer like Streptomyces nogalater NIIST A30.

First report on isolation of 2,3,4-trihydroxy-5-methylacetophenone from palmyra palm (Borassus flabellifer Linn.) syrup, its antioxidant and antimicrobial properties.

The first report on isolation and characterization of 2,3,4-trihydroxy-5-methylacetophenone (1), nicotinamide (2), and uracil (3) from palmyra palm syrup is described. Total phenolic content (TPC) and Total flavonoid content (TFC) of palm syrup were 244.70±5.77(mggallic acid/kg of syrup) and 658.45±27.86(mg quercetin/kg of syrup), respectively. Compound 1 exhibited DPPH radical scavenging activity with an IC50 value of 20.02±0.14µM which was better than ascorbic acid (IC50=22.59±0.30µM). Compound 1 also showed broad spectrum antibacterial activity against Escherichia coli, Mycobacterium smegmatis, Staphylococcus aureus and Staphylococcus simulans.

Expedient Synthesis of Indolo[2,3-b]quinolines, Chromeno[2,3-b]indoles, and 3-Alkenyl-oxindoles from 3,3'-Diindolylmethanes and Evaluation of Their Antibiotic Activity against Methicillin-Resistant Staphylococcus aureus.

Easily accessible 3,3'-diindolylmethanes (DIMs) were utilized to generate a focused library of indolo[2,3-b]quinolines (2), chromeno[2,3-b]indoles (3), and 3-alkenyl-oxindoles (4) under 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative conditions. DIMs with ortho-NHTosyl (NHTs) phenyl group afforded indolo[2,3-b]quinolines (2), whereas DIMs with ortho-hydroxy phenyl groups yielded chromeno[2,3-b]indoles (3) and 3-alkenyl-oxindoles (4). The mild conditions and excellent yields of the products make this method a good choice to access a diverse library of bioactive molecules from a common starting material. Two optimized compounds 2a and 2n displayed excellent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Compound 2a showed the minimum inhibitory concentration values in the concentration between 1 and 4 µg/mL, whereas compound 2n revealed the values of 1-2 µg/mL. Furthermore, both the compounds were highly bactericidal and capable to kill the MRSA completely within 360 min. Collectively, the results suggested that both compounds 2a and 2n possess enormous potential to be developed as anti-MRSA agents.

Pseudopyronine B: A Potent Antimicrobial and Anticancer Molecule Isolated from a Pseudomonas mosselii.

In continuation of our search for new bioactive compounds from soil microbes, a fluorescent Pseudomonas strain isolated from paddy field soil of Kuttanad, Kerala, India was screened for the production of bioactive secondary metabolites. This strain was identified as Pseudomonas mosselii through 16S rDNA gene sequencing followed by BLAST analysis and the bioactive metabolites produced were purified by column chromatography (silica gel) and a pure bioactive secondary metabolite was isolated. This bioactive compound was identified as Pseudopyronine B by NMR and HR-ESI-MS. Pseudopyronine B recorded significant antimicrobial activity especially against Gram-positive bacteria and agriculturally important fungi. MTT assay was used for finding cell proliferation inhibition, and Pseudopyronine B recorded significant antitumor activity against non-small cell lung cancer cell (A549), and mouse melanoma cell (B16F10). The preliminary MTT assay results revealed that Pseudopyronine B recorded both dose- and time-dependent inhibition of the growth of test cancer cell lines. Pseudopyronine B induced apoptotic cell death in cancer cells as evidenced by Acridine orange/ethidium bromide and Hoechst staining, and this was further confirmed by flow cytometry analysis using Annexin V. Cell cycle analysis also supports apoptosis by inducing G2/M accumulation in both A549 and B16F10 cells. Pseudopyronine B treated cells recorded significant up-regulation of caspase 3 activity. Moreover, this compound recorded immunomodulatory activity by enhancing the proliferation of lymphocytes. The production of Pseudopyronine B by P. mosselii and its anticancer activity in A549 and B16F10 cell lines is reported here for the first time. The present study has a substantial influence on the information of Pseudopyronine B from P. mosselii as potential sources of novel drug molecule for the pharmaceutical companies, especially as potent antimicrobial and anticancer agent.

Molecular characterization of forest soil based Paenibacillus elgii and optimization of various culture conditions for its improved antimicrobial activity.

Microorganisms have provided a bounty of bioactive secondary metabolites with very exciting biological activities such as antibacterial, antifungal antiviral, and anticancer, etc. The present study aims at the optimization of culture conditions for improved antimicrobial production of Paenibacillus elgii obtained from Wayanad forest of Western Ghats region of Kerala, India. A bacterial strain isolated from the Western Ghats forest soil of Wayanad, Kerala, India was identified as P. elgii by 16S rRNA gene sequencing. P. elgii recorded significant board spectrum activity against all human and plant pathogenic microorganism tested except Candida albicans. It has been well known that even minor variations in the fermentation medium may impact not only the quantity of desired bioactive metabolites but also the general metabolic profile of the producing microorganisms. Thus, further studies were carried out to assess the impact of medium components on the antimicrobial production of P. elgii and to optimize an ideal fermentation medium to maximize its antimicrobial production. Out of three media [nutrient broth (NA), Luria broth (LB) and Trypticase soy broth (TSB)] used for fermentation, TSB medium recorded significant activity. Glucose and meat peptone were identified as the best carbon and nitrogen sources, which significantly affected the antibiotic production when supplemented with TSB medium. Next the effect of various fermentation conditions such as temperature, pH, and incubation time on the production of antimicrobial compounds was studied on TSB + glucose + meat peptone and an initial pH of 7 and a temperature of 30°C for 3 days were found to be optimum for maximum antimicrobial production. The results indicate that medium composition in the fermentation media along with cultural parameters plays a vital role in the enhanced production of antimicrobial substances.

Characterization of the bioactive metabolites from a plant growth-promoting rhizobacteria and their exploitation as antimicrobial and plant growth-promoting agents.

A plant growth-promoting bacterial strain, PM 105, isolated from a tea plantation soil from the North Eastern region of India was identified as Pseudomonas aeruginosa through classical and 16S ribosomal DNA (rDNA) gene sequencing. Further studies with this strain confirmed broad spectrum antifungal activity against ten human and plant pathogenic fungal pathogens viz. Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus tubingensis, Candida albicans, Colletotrichum gloeosporioides, Fusarium oxysporum, Pencillium expansum, Rhizoctonia solani, Trichophyton rubrum besides growth-promoting property in cowpea (Vigna unguiculata) and pigeon pea (Cajanus cajan). However, no antibacterial property was exhibited by this strain against the four test bacterial pathogens tested in agar overlay method. The crude bioactive metabolites produced by this strain were isolated with three different solvents that exhibited significant antimicrobial and plant growth-promoting activity. Chloroform extract recorded significant antimicrobial and plant growth-promoting activity. Three major compounds viz. 1-hydroxyphenazine, pyocyanin, and phenazine-1-carboxamide were purified and characterized from crude extracts of this strain by various spectral data. The purified compounds recorded prominent antimicrobial activity but failed to establish the plant growth promotion activity in test crop plants under gnotobiotic conditions. Pyocyanin recorded significant antimicrobial activity, and best activity was recorded against T. rubrum (29 mm), followed by P. expansum (28 mm). These results suggest the use of PM 105 as plant growth-promoting agent in crop plants after successful field trials.

Asarones from Acorus calamus in combination with azoles and amphotericin B: a novel synergistic combination to compete against human pathogenic Candida species in vitro.

The increase in drug resistance to current antifungal drugs brings enormous challenges to the management of Candida infection. Therefore, there is a continuous need for the discovery of new antimicrobial agents that are effective against Candida infections especially from natural source especially from medical plants. The present investigation describes the synergistic anticandidal activity of two asarones (∞ and ß) purified from Acorus calamus in combination with three clinically used antifungal drugs (fluconazole, clotrimazole, and amphotericin B). The synergistic anticandidal activities of asarones and drugs were assessed using the checkerboard microdilution and time-kill assays. The results of the present study showed that the combined effects of asarones and drugs principally recorded substantial synergistic activity (fractional inhibitory concentration index (FICI) <0.5). Time-kill study by combination of the minimal inhibitory concentration (MIC) of asarones and drugs (1:1) recorded that the growth of the Candida species was significantly arrested between 0 and 2 h and almost completely attenuated between 2 and 6 h of treatment. These findings have potential implications in adjourning the development of resistance as the anticandidal activity is achieved with lower concentrations of asarones and drugs. The combination of asarones and drugs also significantly inhibit the biofilm formation by Candida species, and this would also help to fight against drug resistance because biofilms formed by Candida species are ubiquitous in nature and are characterized by their recalcitrance toward antimicrobial treatment. The in vitro synergistic activity of asarones and drugs against pathogenic Candida species is reported here for the first time.

In vitro synergistic effect of curcumin in combination with third generation cephalosporins against bacteria associated with infectious diarrhea.

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 µ g/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria in in vitro condition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.