Biochemistry And Microbial Sciences - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/27

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Subject: search.filters.subject.Phytochemicals

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    Obesity and Cancer
    (Springer Singapore, 2021-07-18T00:00:00) Kumar, Shashank; Gupta, Sanjay
    This book highlights the concordance between signaling pathways that are involved in obesity and cancer cross-talks. It describes the role of cytokines, chemokines, growth factors, insulin, and adipokines in the development of obesity-associated cancers. The book reviews the role of inflammatory signaling pathways such as estrogen-mediated signaling, mTOR and AMP-activated protein kinase pathway and the involvement of adaptive and innate immunity, oxidative stress, gene polymorphism, dietary phytochemicals, and miRNAs in obesity and cancer. In addition, it covers the latest research on the drugs and natural therapeutic agents that target obesity-induced cancers and discusses various in vivo models for studying obesity and obesity-associated cancer. Lastly, it analyses the role of genetic polymorphisms in the obesity-related genes that influence cancer development. The book is a useful resource for researchers in the field of cancer, pharmacology, food chemistry, and clinical biochemistry. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.
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    Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study
    (Academic Press, 2021-05-24T00:00:00) Kushwaha, Prem Prakash; Singh, Atul Kumar; Prajapati, Kumari Sunita; Shuaib, Mohd; Gupta, Sanjay; Kumar, Shashank
    Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting Mpro protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ? 100) against SARS-Cov-2 Mpro protein. Molecular docking studies revealed that certain W. somnifera compounds exhibit superior binding potential (?6.16 to ?12.27 kcal/mol) compared to the standard inhibitors (?2.55 to ?6.16 kcal/mol) including nelfinavir and lopinavir. The non-characteristic compounds (quercetin-3-rutinoside-7-glucoside, rutin and isochlorogenic acid B) exhibited higher inhibitory potential in comparison to characteristic W. somnifera compounds withanolide and withanone. Molecular dynamics (MD) simulation studies of the complex for 100 ns confirm favorable and stable binding of the lead molecule. The MMPBSA calculation of the last 10 ns of the protein-ligand complex trajectory exhibited stable binding of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 Mpro. Taken together, the study demonstrates that the non-characteristic compounds present in W. somnifera possess enhanced potential to bind SARS-Cov-2 Mpro active site. We further recommend in vitro and in vivo experimentation to validate the anti-SARS-CoV-2 potential of these lead molecules. � 2021 Elsevier Ltd
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    Characterization of phytochemicals and validation of antioxidant and anticancer activity in some Indian polyherbal ayurvedic products
    (Springer, 2021-03-13T00:00:00) Kushwaha, Prem Prakash; Kumar, Ramesh; Neog, Panchi Rani; Behara, Malay Ranjan; Singh, Pratibha; Kumar, Ajay; Prajapati, Kumari Sunita; Singh, Atul Kumar; Shuaib, Mohd; Sharma, Amit Kumar; Pandey, Abhay Kumar; Kumar, Shashank
    In the present comparative study, the authors studied the antioxidant and anticancer activity of commercially available polyherbal Indian Ayurvedic products namely Divya Sarvakalp Kwath (DSKK), Divya Sanjivani Vati (DSV), Kanchanar Guggulu (KG) and Shakti Drop (SD). Authors also quantified phenolic and flavonoid contents in the samples. Solid powdered samples (DSKK, DSV, and KG) were extracted in methanol and water (1:1) using cold extraction method. Spectrophotometry technique was used to quantify the phytochemicals present in test samples. DSKK showed comparatively higher content of total phenolics (247.65 � 0.05 ?gPGE/g) and flavonoid (34.66 � 0.19 �gQE/mg). Radical scavenging, metal ion chelation and reducing potential of test products were studied using nitric oxide scavenging, DPPH, metal ion chelation, reducing power ability, and phosphomolybdate in vitro antioxidant assays at different concentration. Dose-dependent antioxidant activity was observed in all the test samples at 100�500��g or �l/ml concentration. Anticancer efficacy of the test samples were studied in lung (A549), colon (Colo205), and breast cancer (MCF7) cell lines at different concentrations (10�100��g or �l/ml) using MTT assay. Confocal microscopy was used to reveal the apoptotic induction, mitochondrial membrane integrity disruption and reactive oxygen species production ability of test products in cancer cells. The present study revealed that DSKK possesses comparatively better antioxidant potential and SD has potent anticancer activity against breast cancer cells. � 2021, Society for Plant Research.
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    In silico identification of natural anticancer product and their efficacy in breast cancer cells and cancer stem like cells
    (Central University of Punjab, 2020) Kushwaha, Prem Prakash; Kumar, Shashank
    Breast cancer is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to breast cancer recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Literature survey and in silico study identified Bulbine frutescens (Asphodelaceae), Kurarinone (KU) and 3-O-(E)-p- coumaroylbetulinic acid (CB) as lead plant product/phytochemicals. Methanolic and hexane extract of B. frutescens (BME and BHE respectively), KU and CB were studied for their anticancer activity and notch signaling pathway inhibitory potential in breast cancer cells. Moreover, KU and CB were also studied for their effect in mammosphere. Literature-based identification of methanol soluble phytochemicals of B. frutescens and in silico docking study revealed Bulbineloneside D as a potent notch signaling inhibitor (ϒ-secretase). In silico docking potential of KU and CB were equal to standard gamma secretase inhibitor DAPT (-8.74 kcal/mol). KU-gamma secretase complex showed lower RMSD value, marginal fluctuation in Radius of gyration (Rg), more number of inter hydrogen bonding, and stable secondary structure of the protein which indicates KU as candidate gamma secretase inhibitor (GSI). B. frutescens extracts (IC50 4.8– 28.4 μg/ml), Kurarinone (IC50 0.43-3.42 µM) and CB (IC50 0.99-5.88 µM) significantly decreased cell viability in MDA-MB-231 and T47D cells in time dependent manner. B. frutescens, KU and CB induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in test extract/phytochemicals treated breast cancer cells. Western Blot analysis showed reduced expression of cyclin D1 and increased procaspase 3 protein expression in extract/phytochemicals treated breast cancer cells in time dependent manner. Fluorescence spectrophotometry and confocal microscopy showed extract/phytochemicals induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells at IC50 and sub IC50 concentration. Flow cytometric apoptosis analysis of extract/phytochemicals treated MDA-MB-231 cells showed significant increase in early apoptotic population in comparison to non-treated cells at IC50 and sub IC50 (half of the IC50) concentration. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens, Kurarinone and CB in HEK293 transfected cells at IC50 concentration. Moreover, RT-PCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract/phytochemical treated breast cancer cells in time dependent manner. Western Blot analysis showed reduced notch responsive protein (Hes1, Hey1 and E-cadherin) expression in extract/phytochemical treated breast cancer cells. KU and CB treatment decreased the mammosphere formation ability in MCF-7 cells at IC50 concentration by lowering the notch signaling target proteins (Hes1, Hey1, and E-cadherin) and proteins involved in cancer cell self-renewal (c-Myc, SOX-2, CD44). In conclusion, extract/phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. KU and CB have the ability to downregulate the notch signaling pathway in breast cancer and cancer stem like cells.