Standardised Sonneratia apetala Buch.-Ham. fruit extract inhibits human neutrophil elastase and attenuates elastase-induced lung injury in mice

Chronic obstructive pulmonary disease (COPD) along with asthma is a major and increasing global health problem. Smoking contributes to about 80%–90% of total COPD cases in the world. COPD leads to the narrowing of small airways and destruction of lung tissue leading to emphysema primarily caused by neutrophil elastase. Neutrophil elastase plays an important role in disease progression in COPD patients and has emerged as an important target for drug discovery. Sonneratia apetala Buch.-Ham. is a mangrove plant belonging to family Sonneratiaceae. It is widely found in the Sundarban regions of India. While the fruits of this plant have antibacterial, antifungal, antioxidant and astringent activities, fruit and leaf extracts have been shown to reduce the symptoms of asthma and cough. The aim of this study is to find whether hydro alcoholic fruit extracts of S. apetala inhibit neutrophil elastase and thus prevent the progression of neutrophil elastase-driven lung emphysema. The hydroalcoholic extract, ethanol: water (90:10), of the S. apetala Buch.-Ham. fresh fruits (SAM) were used for neutrophil elastase enzyme kinetic assay and IC50 of the extract was determined. The novel HPLC method has been developed and the extract was standardized with gallic acid and ellagic acid as standards. The extract was further subjected to LC-MS2 profiling to identify key phytochemicals. The standardized SAM extract contains 53 μg/mg of gallic acid and 95 μg/mg of ellagic acid, based on the HPLC calibration curve. SAM also reversed the elastase-induced morphological change of human epithelial cells and prevented the release of ICAM-1 in vitro and an MTT assay was conducted to assess the viability. Further, 10 mg/kg SAM had reduced alveolar collapse induced by neutrophil elastase in the mice model. Thus, in this study, we reported for the first time that S. apetala fruit extract has the potential to inhibit human neutrophil elastase in vitro and in vivo

Development of Derivatives of 3, 3′-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons

Background: The development of 3, 39-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 mM concentration. Methodology/Principal Findings: In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,29diphenyl 3,39-diindolyl methane), DMDIM (2,29-dimethyl 3,39-diindolyl methane) and DMODIM (5,59-dimethoxy 3,39diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. Conclusion: The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents

Woollins Reagent: A Chemoselective Reducing Agent for 1,4-Enediones and 1,4-Ynediones to Saturated 1,4-Diones

Woollins reagent was found to act as a highly chemoselective reagent for the reduction of a wide range of 1,4-enediones and 1,4-ynediones in methanol to afford the corresponding saturated 1,4-diketones in good yields under mild reaction conditions

2-Methyl-pyran-4-one-3-O-β-D-glucopyranoside isolated from leaves of Punica granatum inhibits the TNFα-induced cell adhesion molecules expression by blocking nuclear transcription factor-κB (NF-κB)

Here, we report bioactivity-guided isolation, purification and characterization of a novel compound, 2-methyl-pyran-4-one-3-O-β-D-glucopyranoside (MPG) from the leaves of Punica granatum. The structure of MPG was established on the basis of its detailed spectral analyses. We demonstrated that MPG not only inhibited the expression of cell adhesion molecules but also significantly blocked its functional consequence, that is, the adhesion of neutrophils on human endothelial cells monolayer. To elucidate the molecular mechanism of action of MPG, we showed that MPG decreased the transcript levels of ICAM-1, VCAM-1 and E-selectin genes. Using electrophoretic mobility shift assay (EMSA) and western blot analyses, we demonstrated that MPG significantly blocked both the TNFα-induced translocation and activation of nuclear transcription factor-κB (NF-κB). Thus, MPG could be useful as a novel lead molecule for developing future anti-inflammatory agents

A comprehensive study on crude methanolic extract of Artemisia pallens (Asteraceae) and its active component as effective corrosion inhibitors of mild steel in acid solution

Corrosion inhibition effects of crude methanolic extract of Artemisia pallens on mild steel in 1 mol l1 HCl were studied by weight loss and electrochemical technique. Arbutin, an active principle from A. pallens and the crude methanolic extract exhibited inhibition efficiency of 93% and 98% in 400 mg l1 concentration at 30 C respectively. The results indicated that arbutin in acidic medium acted as good anticorrosive agent synergistically with its hydrolyzed products hydroquinone and D-glucose. Adsorption of both the inhibitors on mild steel surface conformed to the Langmuir isotherm with standard adsorption free energy of 33.07 kJ mol1 for arbutin

Binding of the 9-<em>O</em>-<em>N</em>-aryl/arylalkyl Amino Carbonyl Methyl Substituted Berberine Analogs to tRNA^phe

<div><p>Background</p><p>Three new analogs of berberine with aryl/arylalkyl amino carbonyl methyl substituent at the 9-position of the isoquinoline chromophore along with berberrubine were studied for their binding to tRNA^phe by wide variety of biophysical techniques like spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting, viscosity and isothermal titration calorimetry.</p> <p>Methodology/Principal Findings</p><p>Scatchard binding isotherms revealed that the cooperative binding mode of berberine was propagated in the analogs also. Thermal melting studies showed that all the 9-<i>O</i>-<i>N</i>-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs stabilized the tRNA^phe more in comparison to berberine. Circular dichroism studies showed that these analogs perturbed the structure of tRNA^phe more in comparison to berberine. Ferrocyanide quenching studies and viscosity results proved the intercalative binding mode of these analogs into the helical organization of tRNA^phe. The binding was entropy driven for the analogs in sharp contrast to the enthalpy driven binding of berberine. The introduction of the aryl/arylalkyl amino carbonyl methyl substituent at the 9-position thus switched the enthalpy driven binding of berberine to entropy dominated binding. Salt and temperature dependent calorimetric studies established the involvement of multiple weak noncovalent interactions in the binding process.</p> <p>Conclusions/Significance</p><p>The results showed that 9-<i>O</i>-<i>N</i>-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs exhibited almost ten folds higher binding affinity to tRNA^phe compared to berberine whereas the binding of berberrubine was dramatically reduced by about twenty fold in comparison to berberine. The spacer length of the substitution at the 9-position of the isoquinoline chromophore appears to be critical in modulating the binding affinities towards tRNA^phe.</p> </div

Plots of variation of temperature dependent thermodynamic parameters.

<p>(A) Plot of variation of enthalpy of binding (Δ<i>H⁰</i>) with temperature for binding of analog B2 (▪), B3 (•) and B4 (▴) to tRNA. (B) Plot of variation of <i>ΔG⁰</i> (open symbols) and <i>ΔH⁰</i> (closed symbols) versus <i>TΔ</i>S<i>⁰</i> for the binding of analogs B2 (▪), B3 (•) and B4 (▴) to tRNA, respectively.</p

Thermodynamic parameters for the association of alkaloids with tRNA from ITC^a.

a<p>All the data in this table are derived from ITC experiments conducted in citrate-phosphate buffer of 10 mM [Na⁺], pH 7.0 and are average of four determinations. <i>K_a</i> and Δ<i>H⁰</i> values were determined from ITC profiles fitting to Origin 7.0 software as described in the text. The values of Δ<i>G⁰</i> were determined using the equations and Δ<i>G⁰</i> = Δ<i>H⁰-T</i>Δ<i>S⁰</i>. N is the stoichiometry of binding. Analog B1 produced only background heat hence the data was not determinable. All the ITC profiles were fit to a model of single binding sites.</p