Molecular docking analysis of compounds from Justica adhatoda L with glycogen synthase kinase-3 β

Jayaraman, Selvaraj; Vishnupriya, V.; Sreekandan, Radhika Nalinakumari; Mohan, Surapaneni Krishna; Suga, Sumetha Suga Deiva; Kamaraj, Devakumar; Mohandoss, Sonaimuthu; Rajagopal, Ponnulakshmi

doi:10.6026/97320630016893

Cited by 2 publications

(3 citation statements)

References 16 publications

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“…Among these targets, 20 targets of diosgenin and stigmasterol were identified. Another two targets of diosgenin and stigmasterol, namely, GSK-3β and ESR1, were also included for further analysis according to previous studies ( Jayaraman et al, 2020 ; Wang et al, 2021a ). Besides, 1179 NAFLD-related targets were collected from the GeneCards database, and then verified in the DisGeNET database.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the TCMSP database and encyclopedia of traditional Chinese medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/ ) database were used to obtain the targets of the screened components. The results were then combined with the corresponding literature search results ( Jayaraman et al, 2020 ; Wang et al, 2021a ). Finally, the component targets were integrated into standard gene symbol using the Uniport platform ( https://www.uniprot.org/ ) ( jing et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

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Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein–protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3β might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo

et al. 2022

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“…The compound was also found to have good ADMET properties which provides it with further validation as an anti-viral agent in treating SARS-CoV-2 infection [ 40 , 41 , 42 ]. In a study conducted by Jayaraman et al, they concluded that ethambutol, pyrazinamide, vasicoline and stigmasterol have anti-diabetic effects when docked against Glycogen synthase kinase-3; these compounds were derived from J. adhatoda [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders

et al. 2023

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The field of drug discovery has recognized the significance of computer-aided drug design. Recent advancements in structure identification and characterization, bio-computational science and molecular biology have significantly contributed to the development of novel treatments for various diseases. Alzheimer’s disease is prevalent in over 50 million affected people, with the pathological condition of amyloidal plaque formation by the beta-amyloidal peptide that results in lesions of the patient’s brain, thus making the target prediction and treatment a hurdle. In this study, we evaluated the potential of 54 bioactive compounds from Justicia adhatoda L. and Sida cordifolia L. identified through LC-MS/MS against the β-site amyloid precursor cleaving enzyme (beta-secretase) that results in the formation of amyloidal plaques. To study the drug-likeness of the phytocompounds, Lipinski’s rule of five for ADME profiling and toxicity prediction was performed. Molecular docking was performed using auto-dock tool of PyRx software; molecular dynamic simulations were performed using the Schrodinger suite. Molecular docking against BACE-1 protein revealed that hecogenin, identified from S. cordifolia has a broad spectrum of pharmacological applications and a binding affinity score of −11.3 kcal/Mol. The Hecogenin–BACE-1 protein complex was found to be stable after 30 ns of MD simulation, resulting in its substantial stability. Further studies focusing on the in vivo neuroprotective activity of hecogenin against the disease will pave the way for efficient drug discovery from natural sources in a precise manner.

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Molecular docking analysis of compounds from Justica adhatoda L with glycogen synthase kinase-3 β

Cited by 2 publications

References 16 publications

Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo

Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo

Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders

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