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  • Ravichandiran, Velayutham  (5)
  • 1
    Online Resource
    Online Resource
    Epigenetic modification and therapeutic targets of diabetes mellitus
    Portland Press Ltd. ; 2020
    In:  Bioscience Reports Vol. 40, No. 9 ( 2020-09-30)
    Details
    In: Bioscience Reports, Portland Press Ltd., Vol. 40, No. 9 ( 2020-09-30)
    Abstract: The prevalence of diabetes and its related complications are increasing significantly globally. Collected evidence suggested that several genetic and environmental factors contribute to diabetes mellitus. Associated complications such as retinopathy, neuropathy, nephropathy and other cardiovascular complications are a direct result of diabetes. Epigenetic factors include deoxyribonucleic acid (DNA) methylation and histone post-translational modifications. These factors are directly related with pathological factors such as oxidative stress, generation of inflammatory mediators and hyperglycemia. These result in altered gene expression and targets cells in the pathology of diabetes mellitus without specific changes in a DNA sequence. Environmental factors and malnutrition are equally responsible for epigenetic states. Accumulated evidence suggested that environmental stimuli alter the gene expression that result in epigenetic changes in chromatin. Recent studies proposed that epigenetics may include the occurrence of ‘metabolic memory’ found in animal studies. Further study into epigenetic mechanism might give us new vision into the pathogenesis of diabetes mellitus and related complication thus leading to the discovery of new therapeutic targets. In this review, we discuss the possible epigenetic changes and mechanism that happen in diabetes mellitus type 1 and type 2 separately. We highlight the important epigenetic and non-epigenetic therapeutic targets involved in the management of diabetes and associated complications.
    Type of Medium: Online Resource
    ISSN: 0144-8463 , 1573-4935
    URL: Article
    DOI: 10.1042/BSR20202160
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2020
    detail.hit.zdb_id: 2014993-1
    SSG: 12
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  • 2
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    Screening of Azadirachta indica phytoconstituents as GSK-3β inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study
    Informa UK Limited ; 2022
    In:  Journal of Biomolecular Structure and Dynamics Vol. 40, No. 23 ( 2022-12-19), p. 12827-12840
    Details
    In: Journal of Biomolecular Structure and Dynamics, Informa UK Limited, Vol. 40, No. 23 ( 2022-12-19), p. 12827-12840
    Type of Medium: Online Resource
    ISSN: 0739-1102 , 1538-0254
    URL: Article
    DOI: 10.1080/07391102.2021.1977705
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2085732-9
    SSG: 12
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  • 3
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    Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 20 ( 2020-10-10), p. 4604-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 20 ( 2020-10-10), p. 4604-
    Abstract: The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25204604
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 4
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    Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 19 ( 2022-09-24), p. 11254-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 19 ( 2022-09-24), p. 11254-
    Abstract: The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231911254
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 23 ( 2022-11-25), p. 8222-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 23 ( 2022-11-25), p. 8222-
    Abstract: Natural products are being targeted as alternative anticancer agents due to their non-toxic and safe nature. The present study was conducted to explore the in vitro anticancer potential of Justicia adhatoda (J. adhatoda) leaf extract. The methanolic leaf extract was prepared, and the phytochemicals and antioxidant potential were determined by LCMS analysis and DPPH radical scavenging assay, respectively. A docking study performed with five major alkaloidal phytoconstituents showed that they had a good binding affinity towards the active site of NF-κB. Cell viability assay was carried out in five different cell lines, and the extract exhibited the highest cytotoxicity in MCF-7, a breast cancer cell line. Extract-treated cells showed a significant increase in nitric oxide and reactive oxygen species production. Cell cycle analysis showed an arrest in cell growth at the Sub-G0 phase. The extract successfully inhibited cell migration and colony formation and altered mitochondrial membrane potential. The activities of superoxide dismutase and glutathione were also found to decrease in a dose-dependent manner. The percentage of apoptotic cells was found to increase in a dose-dependent manner in MCF-7 cells. The expressions of caspase-3, Bax, and cleaved-PARP were increased in extract-treated cells. An increase in the expression of NF-κB was found in the cytoplasm in extract-treated cells. J. adhatoda leaf extract showed a potential anticancer effect in MCF-7 cells.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27238222
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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