scholarly journals Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 639 ◽  
Author(s):  
Md. Abdul Hannan ◽  
Raju Dash ◽  
Abdullah Al Mamun Sohag ◽  
Il Soo Moon
Keyword(s):  
Protein Kinase ◽  
In Silico ◽  
In Silico Analysis ◽  
Integrated System ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Present System ◽  
Toll Like Receptor ◽  
System Pharmacology ◽  
Silico Analysis

Fucosterol is an algae-derived unique phytosterol having several medicinal properties, including antioxidant, anti-inflammatory, anticholinesterase, neuroprotective, and so on. Accumulated evidence suggests a therapeutic promise of fucosterol in neurodegeneration; however, the in-depth pharmacological mechanism of its neuroprotection is poorly understood. Here, we employed system pharmacology and in silico analysis to elucidate the underlying mechanism of neuropharmacological action of fucosterol against neurodegenerative disorders (NDD). Network pharmacology revealed that fucosterol targets signaling molecules, receptors, enzymes, transporters, transcription factors, cytoskeletal, and various other proteins of cellular pathways, including tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), neurotrophin, and toll-like receptor (TLR) signaling, which are intimately associated with neuronal survival, immune response, and inflammation. Moreover, the molecular simulation study further verified that fucosterol exhibited a significant binding affinity to some of the vital targets, including liver X-receptor-beta (LXR-), glucocorticoid receptor (GR), tropomyosin receptor kinase B (TrkB), toll-like receptor 2/4 (TLR2/4), and β -secretase (BACE1), which are the crucial regulators of molecular and cellular processes associated with NDD. Together, the present system pharmacology and in silico findings demonstrate that fucosterol might play a significant role in modulating NDD-pathobiology, supporting its therapeutic application for the prevention and treatment of NDD.

Integrated System Pharmacology and In Silico Analysis Elucidating Neuropharmacological Actions of Withania somnifera in the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 19 (7) ◽  
pp. 541-556
Author(s):  
Md. Abdul Hannan ◽  
Raju Dash ◽  
Md. Nazmul Haque ◽  
Sung Min Choi ◽  
Il Soo Moon
Keyword(s):  
Alzheimer’S Disease ◽  
In Silico ◽  
Withania Somnifera ◽  
In Silico Analysis ◽  
Toll Like Receptor ◽  
Protein Targets ◽  
Withanolide A ◽  
Gsk 3Β ◽  
Silico Analysis ◽  
Bace 1

Background: Withania somnifera (WS), also referred to as Medhya Rasayana (nootropic or rejuvenating), has traditionally been prescribed for various neurological ailments, including dementia. Despite substantial evidence, pharmacological roles of WS, neither as nootropic nor as an antidementia agent, are well-understood at the cellular and molecular levels. Objectives: We aimed at elucidating the pharmacological action mechanisms of WS root constituents against Alzheimer’s Disease (AD) pathology. Methods: Various bioinformatics tools and resources, including DAVID, Cytoscape, NetworkAnalyst and KEGG pathway database were employed to analyze the interaction of WS root bioactive molecules with the protein targets of AD-associated cellular processes. We also used a molecular simulation approach to validate the interaction of compounds with selected protein targets. Results: Network analysis revealed that β-sitosterol, withaferin A, stigmasterol, withanolide A, and withanolide D are the major constituents of WS root that primarily target the cellular pathways such as PI3K/Akt signaling, neurotrophin signaling and toll-like receptor signaling and proteins such as Tropomyosin receptor Kinase B (TrkB), Glycogen Synthase Kinase-3β (GSK-3β), Toll-Like Receptor 2/4 (TLR2/4), and β-secretase (BACE-1). Also, the in silico analysis further validated the interaction patterns and binding affinity of the major WS compounds, particularly stigmasterol, withanolide A, withanolide D and β-sitosterol with TrkB, GSK-3β, TLR2/4, and BACE-1. Conclusion: The present findings demonstrate that stigmasterol, withanolide A, withanolide D and β-sitosterol are the major metabolites that are responsible for the neuropharmacological action of WS root against AD-associated pathobiology, and TrkB, GSK-3β, TLR2/4, and BACE-1 could be the potential druggable targets.

scholarly journals Highlighting the Role of Cdk6 Associated MicroRNAs in Cancer Treatment Using In Silico Approaches

2020 ◽  
pp. 1-14
Author(s):  
Sidra Batool ◽  
Muhammad Sibte Hasan Mahmood ◽  
Tiyyaba Furqan ◽  
Sidra Batool
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
In Silico ◽  
Drug Target ◽  
In Silico Analysis ◽  
Kinase Domain ◽  
Protein Kinase Domain ◽  
Over Expression ◽  
Silico Analysis

MicroRNAs (miRNAs) are small non-coding RNA’s that controls the regulation of a gene. Due to the over expression or under expression of miRNAs it leads to cause tumor or any other type of cancers such as, melanoma, lymphoma, cardiovascular issue, breast cancer etc. So, miRNAs can be used as a drug target for cancer therapy. This study aimed to check binding cavities of microRNA's involved in regulation of CDK6 protein. There are 23 different families of miRNAs that are involved in regulation of CDK6. Each family has one or more miRNAs. All these miRNAs are involved in the up regulation or downregulation of a gene, which lead to different type of cancers. All miRNAs of each family docked with mRNA CDK6 protein. After performing in silico analysis of binding interactions of mRNA with miRNAs the results were further refined by their comparison with information regarding their energies, interaction of the mRNA and miRNAs. The results show that all miRNAs lie in Protein Kinase domain, but the residues that lie is different within the families and across the families.

scholarly journals The associations between Toll-like receptor 4 gene polymorphisms and hepatitis C virus infection: a systematic review and meta-analysis

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Narttaya Chaiwiang ◽  
Teera Poyomtip
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Silico ◽  
Meta Analysis ◽  
In Silico Analysis ◽  
Hcv Infection ◽  
Toll Like Receptor ◽  
Silico Analysis

Abstract Background and objective: The hepatitis C virus (HCV) is able to cause a life-threatening disease relating to lethal hepatocellular carcinoma. Previous, Toll-like receptor polymorphisms were proposed as promising biomarker for HCV-related hepatocellular carcinoma and disease progression. This study aimed to summarize the association of TLR4 polymorphisms and HCV infection through meta-analysis. Methods: We applied a systematic review and meta-analysis performed by using PubMed, EMBASE and Web of Science searches. The Modified Newcastle-Ottawa scale was used for quality assessment. The odd-ratio (OR) and 95% confidence interval (CI) were calculated to assess the association. In silico analysis was applied for proposing the function as microRNA (miRNA) of non-coding polymorphism. Finally, the miRNA target was predicted and annotated to suggest the possible relationship between polymorphism and HCV infection. Results: Our meta-analysis incorporated seven studies involving rs4986791, rs4986790 and rs2149356. No association exists between rs4986791 and HCV infection. However, the heterozygous model (AG vs GG) of rs4986790 significantly associates with HCV infection (OR = 0.33, 95% CI = 0.21–0.49, P<0.0001). Moreover, the rs2149356 TG genotype also associates with HCV infection in the over-dominant model (TG vs TT+TG: OR = 0.54, 95% CI = 0.40–0.75). In silico analysis of rs2149356G allele showed that this mutation is siRNA, which targets the set of genes, especially in the autophagy pathway. Conclusion: We demonstrated that rs4986790 and rs2149356 are associated with HCV infection.

scholarly journals Momordica charantia L. Extract Protects Hippocampal Neuronal Cells against PAHs-Induced Neurotoxicity: Possible Active Constituents Include Stigmasterol and Vitamin E

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2368
Author(s):  
Nattaporn Pattarachotanant ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Vitamin E ◽  
In Silico ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
In Silico Analysis ◽  
Momordica Charantia ◽  
Mitogen Activated Protein Kinase ◽  
Active Components ◽  
Neuroprotective Effects ◽  
Silico Analysis

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species’ (ROS’) production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.

scholarly journals Toll-like receptor 9 interaction with CpG ODN – An in silico analysis approach

2013 ◽  
Vol 10 (1) ◽  
Author(s):  
Wei Zhou ◽  
Yan Li ◽  
Xichun Pan ◽  
Yuan Gao ◽  
Beiping Li ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Analysis Approach ◽  
Cpg Odn ◽  
Toll Like Receptor ◽  
Silico Analysis
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