Designing Click One-Pot Synthesis and Antidiabetic Studies of 1,2,3-Triazole Derivatives.

In the present study, a new series of 1,2,3-triazole derivatives was synthesized via a click one-pot reaction. The synthesized compounds were found to be active during molecular docking studies against targeted protein 1T69 by using the Molecular Operating Environment (MOE) software. The designed and synthesized compounds were characterized by using FT-IR, 1H-NMR and LC-MS spectra. The synthesized triazole moieties were further screened for their α-amylase and α-glucosidase inhibitory activities. The preliminary activity analysis revealed that all the compounds showed good inhibition activity, ranging from moderate to high depending upon their structures and concentrations and compared to the standard drug acarbose. Both in silico and in vitro analysis indicated that the synthesized triazole molecules are potent for DM type-II. Out of all the compounds, compound K-1 showed the maximum antidiabetic activity with 87.01% and 99.17% inhibition at 800 µg/mL in the α-amylase and α-glucosidase inhibition assays, respectively. Therefore these triazoles may be further used as promising molecules for development of antidiabetic compounds.

Inhibition of mouse embryonic stem cell proliferation and induction of differentiation by natural products isolated from Rhazya stricta Decne.

Embryonic stem cells provide an ideal system to study various therapies for serious human diseases such as juvenile diabetes, neurodegenerative diseases, heart diseases and cancer. Synthetic or natural compounds that affect cell proliferation and/or differentiation of embryonic stem cells are of great value. Focus of the current project was upon the isolation and evaluation of natural components from a medicinal plant; Rhazya stricta on proliferation/ differentiation potential of embryonic stem cells. For this purpose, after a series of fractionation and purification steps, 7 compounds named as RS1-RS7 were isolated from aerial parts of the plant. The effects of these compounds were evaluated on the morphology and rate of cell proliferation of mouse naive embryonic stem cells. Only RS7 inhibited the proliferation of cell and reduced the induction of differentiation of cell. The qPCR analysis confirmed that the expression of the selected pluripotency markers (Oct4, Nanog and Sox2) was down regulated by RS7 treatment as compared to control. Furthermore, upon withdraw of Leukemia inhibitory factor (lif) from medium; effect of RS7 to promote differentiation was enhanced. Through structure elucidation studies, RS7 was found to be ursolic acid. This study first time shows the effect of natural compounds of Rhazya stricta Decne. on mouse embryonic stem cells.

Ameliorating role of methanolic leaves extract of Fraxinus xanthoxyloides against CCl4-challanged nephrotoxicity in rats.

Roots, bark, stem/twigs, and leaves of Fraxinus xanthoxyloides are being used regionally for the cure of malaria, jaundice, internal injuries, pneumonia, pain, rheumatism and also in fracture of bones. Our objective was to assess the methanolic leaves extract of F. xanthoxyloides for its antioxidant capability against oxidative stress induced by carbon tetrachloride (CCl4) in the kidney of Sprague-Dawley rats. Duration of this experiment was 30 days and doses were given on alternative days. Urine of rats was assessed for kidney function and renal tissues for antioxidant enzymes activity, biochemical markers, comet assay and histopathology. Enhanced urinary creatinine, urobilinogen levels and decreased creatinine clearance, protein contents, and albumin levels were observed by CCl4 administration when matched to controls. CCl4 injection also decreased the level of reduced glutathione, catalase, super oxide dismutase, peroxidase, glutathione s-transferase, glutathione reductase, and tissue protein while elevated the levels of thiobarbituric acid reactive substances, DNA damages and H2O2 in renal tissues of experimental animals. Co-treatment of FXM and silymarin, lead to the restoration of all the above tested parameters of kidney. Through this study we affirmed the ameliorating role of F. xanthoxyloides in oxidative stress affiliated disorders of kidney.

Plants as Antileishmanial Agents: Current Scenario.

Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level. Copyright © 2016 John Wiley & Sons, Ltd.

Hedera nepalensis K. Koch: A Novel Source of Natural Cancer Chemopreventive and Anticancerous Compounds.

Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer-cell lines: MCF-7, MDA-MB-231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n-hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n-hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 µM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 µM. HPLC-DAD-based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents.

Age, gender, and infectious status-wise assessments of hematological parameters among patients with dengue infection.

Background: The aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. Methods: The recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. Results: The findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. Conclusion: In conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.

Novel copper complexes of metronidazole and metronidazole benzoate: synthesis, characterization, biological and computational studies.

Synthesis and characterization of novel copper complexes of metronidazole benzoate (MTZ Benz), metronidazole (MTZ) in the presence of another ligand; dichloroacetic acid (DCA) were compared and reported in the present work. Different bacterial and fungus strains were ascertained to evaluate the biological potency of the synthesized complexes, that is, Escherichia coli, Bordetella bronceptica, Staphylococcus epidermidis, Baccilus pumilus, Staphylococcus aureus and yeast strain Saccharomyces cerevisiae. Agar diffusion method was employed to investigate in vitro antibacterial activities of the synthesized metal complexes and the tested parent ligands. α-Amylase and α-glucosidase inhibition studies of the synthesized complexes were also carried out. The antibacterial potential and α-amylase and α-glucosidase inhibition studies of complexes were further investigated by molecular docking studies, which supported the experimental results. Significant α-amylase and α-glucosidase inhibition activities were shown by the synthesized complexes. S-1 and S-5 were found to be most inhibitors of α-amylase and α-glucosidase having IC50 42.50, 44.80 and 4.52 µg/mL, 4.80 µg/mL, respectively. The newly synthesized copper complexes showed overall better biological activities compared to each parent ligands used.Communicated by Ramaswamy H. Sarma.

Cost-effective fabrication, antibacterial application and cell viability studies of modified nonwoven cotton fabric.

In the present work, nonwoven cotton fabric was modified for antibacterial applications using low-cost and eco-friendly precursors. The treatment of fabric with alkali leads to the formation of active sites for surface modification, followed by dip coating with silver nanoparticles and chitosan. The surface was chlorinated in the next step to transform amide (N-H) groups in chitosan into N-halamine (N-Cl). The modified and unmodified surfaces of the nonwoven cotton fabric have been characterized by FTIR, SEM, and XRD. The active chlorine loading is measured with iodine/sodium thiosulphate. The antimicrobial activity and cell toxicity assay were carried out with and without modifications of nonwoven cotton fabric. The antimicrobial efficacies of loaded fabric were evaluated against four bacterial species (Micrococcus luteus, Staphylococcus aureus, Enterobacter aerogenes, and E.coli). It was found that modified fabric exhibited superior efficiency against gram-positive and gram-negative bacterial strains as compared to their bulk counterparts upon exposure without affecting strength and integrity of fabric. The overall process is economical for commercial purposes. The modified fabric can be used for antimicrobial, health, and food packaging industries, and in other biomedical applications.

Proteomic profiling the molecular signatures of plectranthoic acid in prostate cancer cells.

Among cancers, prostate cancer (PCa) is frequently detected solid tumor and a growing problem for the male population, globally. Newer treatment modalities with specific targets are required for management. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Natural metabolite i.e. plectranthoic acid (PA), inhibits the proliferation of PCa cells and has potent anti-cancer potential. Herein, we aim to identify the molecular signatures of PA. Proteins from control and PA-treated PCa cells were analysed using high-throughput labeled free proteomics approach. Data was processed with the SIEVE software and thoroughly analysed by using Ingenuity pathway analysis (IPA) and PANTHER. A total of 98 unique peptides, showing >2 fold change, were identified. Results indicated that PA modulates oncogenic pro-survival and pro-apoptotic signaling pathways in PCa cells. mTOR was the major canonical pathway targeted by PA, the inhibition of which was likely to induce PA mediated apoptosis. Moreover, PA interacts with the rapamycin binding domain of mTOR, demonstrated by the molecular dynamic (MD) simulation and binding free energy calculations. Furthermore, the biological process moderated by PA with a high percentage was a metabolic process. Taken together, PA appears to have pleiotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness. SIGNIFICANCE: Studies on the mechanism of action of therapeutic agents are crucial for drug development. These studies support the selection of a therapeutic agent, appropriate models of its efficacy, and designing of further experiments. Furthermore, information on mechanism of action may suggest strategies for combination therapies. In this regard Proteomics provide the platform for comprehensive understanding of the molecular action mechanisms of newly discovered therapeutic agents. Current research highlights the new insights into mode of action of novel therapeutic metabolite i.e. Plectranthoic acid (PA). Using labeled free proteomics approach we extracted the underlying mechanisms for the anticancer activity of PA using prostate cancer model. The result of the study will pay the way for further investigations on this potent natural compound in different cancers and will provide a root for its development as a lead.

The protective potential of a Fraxinus xanthoxyloides ethyl acetate fraction against CCl4-induced oxidative stress in the cardiac tissue of rats.

Secondary metabolites present in medicinal plants offer a golden opportunity to fight different ailments, such as cancer, infections, diabetes, neurodegenerative and cardiovascular diseases, etc. The traditional use of various parts of Fraxinus xanthoxyloides is known to serve as a cure for pneumonia, pain, jaundice, malaria, fracturing of bones, and internal wounds. The aim of this research was to validate the antioxidant and cardio-protective properties of F. xanthoxyloides leaves. The antioxidant potential was evaluated by employing different assays on the crude methanol extract, as well as its derived fractions. The extract/fraction that showed significant activity was further investigated for the presence of phytochemicals using high performance liquid chromatography-diode array detector (HPLC-DAD) analysis and also for cardio-protective potential. In the case of the antioxidant potential, the ethyl acetate fraction (FXE) was demonstrated to have the most potent total antioxidant (26.3 ± 2.4 AAE µg mg-1), hydroxyl ion scavenging (IC50 = 7.9 ± 0.9 µg mg-1), ferrous ion chelating (IC50 = 28.2 ± 2.7 µg mg-1) and nitric oxide scavenging (IC50 = 32.5 ± 2.9 µg mg-1) effects among all of the extract/fractions, whereas in the case of DPPH (IC50 = 17.5 ± 2.7 µg mg-1) and the reducing power assay (16.7 ± 2.8 GAE µg mg-1), promising antioxidant potential was shown by the n-butanol fraction. The presence of different concentrations of rutin, caffeic acid, catechin, and gallic acid was observed in the high performance liquid chromatography (HPLC) profile of FXE. Furthermore, in in vivo experimentation, the oral administration of FXE and silymarin significantly restored the CCl4-induced increase in the levels of creatine kinase, creatine kinase-MB, cholesterol and triacylglycerides when compared with the untreated group. FXE and silymarin treatment also restored the levels of the tissue antioxidant enzymes, for example glutathione-S-transferase, glutathione reductase, catalase, peroxidase and superoxide dismutase. Furthermore, significantly lower levels of reduced glutathione and enhanced levels of lipid peroxides, hydrogen peroxide, comet length and DNA damages were observed after CCl4 administration in the cardiac tissue of rats. FXE was able to restore these biochemical parameters, as well as the histological status of heart tissue. Based upon the present investigation, we concluded that F. xanthoxyloides leaves may have cardio-protective potential similar to silymarin against CCl4 induced injuries owing to its antioxidant constituents.