Systems pharmacology and molecular docking strategies prioritize natural molecules as antiinflammatory agents

Nair, Anjana S.; Paliwal, Anupam

doi:10.1016/b978-0-12-819218-4.00016-x

Cited by 4 publications

(4 citation statements)

References 108 publications

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“…Other drug candidates include trimethoprim, which inhibits the activity of the dihydrofolate reductase enzyme, which has long been a target for anti-inflammatory and anti-cancer treatment [ 105 , 106 ]. Another is a cholinergic receptor agonist, pentolinium, which is commonly used as an antihypertensive.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases

Pasamba,

Orda,

Villanueva

et al. 2024

Biology

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Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to long-term physiological consequences. This study was able to identify highly preserved modules and key hub genes that are mainly associated with gynecological diseases, represented by endometriosis (EM), ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), through the weighted gene co-expression network analysis (WGCNA) of microarray datasets sourced from the Gene Expression Omnibus (GEO) database. Five highly preserved modules were observed across the EM (GSE51981), OC (GSE63885), CC (GSE63514), and EC (GSE17025) datasets. The functional annotation and pathway enrichment analysis revealed that the highly preserved modules were heavily involved in several inflammatory pathways that are associated with transcription dysregulation, such as NF-kB signaling, JAK-STAT signaling, MAPK-ERK signaling, and mTOR signaling pathways. Furthermore, the results also include pathways that are relevant in gynecological disease prognosis through viral infections. Mutations in the ESR1 gene that encodes for ERα, which were shown to also affect signaling pathways involved in inflammation, further indicate its importance in gynecological disease prognosis. Potential drugs were screened through the Drug Repurposing Encyclopedia (DRE) based on the up-and downregulated hub genes, wherein a bacterial ribosomal subunit inhibitor and a benzodiazepine receptor agonist were the top candidates. Other drug candidates include a dihydrofolate reductase inhibitor, glucocorticoid receptor agonists, cholinergic receptor agonists, selective serotonin reuptake inhibitors, sterol demethylase inhibitors, a bacterial antifolate, and serotonin receptor antagonist drugs which have known anti-inflammatory effects, demonstrating that the gene network highlights specific inflammatory pathways as a therapeutic avenue in designing drug candidates for gynecological diseases.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases

Pasamba,

Orda,

Villanueva

et al. 2024

Biology

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“…The compounds gingerol and shagaol are abundant in red ginger and have been found to possess biological activity as interleukin receptor inhibitors, as indicated in Table 2. To determine the biological activity of these compounds and compare it with that of ibuprofen, the 3D structure of the target protein, interleukin 10 receptor, was prepared by selecting the protein structure in its active form, which is still bound to the ligand (Murugesan et al, 2020;Nair & Paliwal, 2021). The resulting visualization shows the interaction between amino acid residues and ligands, and the presence of amino acid interactions allows for intermediate contact with the interleukin 10 receptor, thereby exhibiting heat inhibition activity.…”

Section: Interaction Of Target Proteins and Ligan Compoundsmentioning

confidence: 99%

Antipyretic Drug Candidates Through Reverse Docking Techniques Used In Science Learning

Iksan,

Yusuf,

Fitriani B

et al. 2023

jppipa, pendidikan ipa, fisika, biologi, kimia

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Red ginger (Zingiber officinale var. Rubrum) is a commonly used rhizome known for its fragrant and spicy taste. It contains gingerol and shogaol compounds that have antipyretic effects by inhibiting prostaglandin formation and stimulating the production of interleukin-10, an endogenous antipyretic. This study aimed to evaluate the potential of gingerol and shogaol compounds as antipyretic drug candidates through reverse docking techniques targeting interleukin-10 (IL-10). Ten natural compounds from red ginger were predicted for their potential as antipyretic drugs and docked with the IL-10 receptor protein using various computer programs. The molecular docking results showed that (6)-shogaol had four amino acid bond residues that were the same as the ibuprofen control compound, indicating its potential as an antipyretic drug candidate. Furthermore, (6)-shogaol had the same binding affinity as the control compound and was safe for oral consumption based on pharmacokinetic and toxicity tests using Lipinski's Rule, Toxtree, and admet-T. These findings suggest that (6)-shogaol is a promising antipyretic drug candidate compared to other compounds. In conclusion, this study identified the potential of (6)-shogaol as an antipyretic drug candidate through reverse docking techniques targeting interleukin-10. Red ginger could provide a natural alternative for antipyretic drugs, and further research is recommended to explore the role of gingerol and shogaol compounds in targeting other proteins

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“…For instance, C11 has an antiallergic activity and can inhibit melanoma formation (Matsumoto et al, 2015). C7 and C8, as well as some other diarylheptanoid compounds, have a good antioxidant and antiinflammatory activity (Alonso-Amelot, 2016; Jivishov et al, 2020;Nair and Paliwal, 2021;Vanucci-bacqu and Bedosbelval, 2021). Free radicals, inflammation, and thrombosis are interrelated in complex ways to each other.…”

Section: In Vitro Thr Inhibition Assaysmentioning

confidence: 99%

Identifying of Anti-Thrombin Active Components From Curcumae Rhizoma by Affinity-Ultrafiltration Coupled With UPLC-Q-Exactive Orbitrap/MS

et al. 2021

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Recent studies concerning products that originate from natural plants have sought to clarify active ingredients, which both explains the mechanisms of the function and aids in quality control during production. As a traditional functional plant, Curcumae Rhizoma (CR) has been proven to be effective in promoting blood circulation and removing blood stasis. However, the components that play a role in its huge compound library are still unclear. The present study aimed to develop a high-throughput screening method to identify thrombin inhibitors in CR and validate them by in vitro and in vivo experiments. The effect of CR on thrombin in HUVECs cells was determined by ELISA, then an affinity-ultrafiltration-UPLC-Q-Exactive Orbitrap/MS approach was applied. Agatroban and adenosine were used as positive and negative drugs respectively to verify the reliability of the established method. The in vitro activity of the compounds was determined by specific substrate S-2238. The in vivo effect of the active ingredients was determined using zebrafish. Molecular docking was used to understand the internal interactions between compounds and enzymes. ELISA results showed that CR had an inhibitory effect on thrombin. The screening method established in this paper is reliable, by which a total of 15 active compounds were successfully identified. This study is the first to report that C7, 8, and 11 have in vitro thrombin-inhibitory activity and significantly inhibit thrombosis in zebrafish models at a safe dose. Molecular docking studies were employed to analyze the possible active binding sites, with the results suggesting that compound 16 is likely a better thrombin inhibitor compared with the other compounds. Based on the affinity-ultrafiltration-UPLC-Q-Exactive Orbitrap/MS approach, a precisely targeted therapy method using bio-active compounds from CR might be successfully established, which also provides a valuable reference for targeted therapy, mechanism exploration, and the quality control of traditional herbal medicine.

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Systems pharmacology and molecular docking strategies prioritize natural molecules as antiinflammatory agents

Cited by 4 publications

References 108 publications

Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases

Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases

Antipyretic Drug Candidates Through Reverse Docking Techniques Used In Science Learning

Identifying of Anti-Thrombin Active Components From Curcumae Rhizoma by Affinity-Ultrafiltration Coupled With UPLC-Q-Exactive Orbitrap/MS

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