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Volume 21, Issue 3
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Plants represent a rich reservoir of bioactive compounds with established therapeutic value in diverse diseases. Notably, the Toll-like receptor-4 (TLR-4) signaling pathway plays a pivotal role in inflammation. Upon engagement with pro-inflammatory ligands like lipopolysaccharide, TLR-4 triggers downstream cascades involving nuclear factor ĸappa B and mitogen-activated protein kinases. This signaling cascade ultimately dictates the onset and progression of inflammatory diseases. Therefore, targeting TLR-4 signaling offers a promising therapeutic approach for managing inflammatory disorders.

Methods

This study investigated the potential of rhizome phytocompounds, a traditional medicinal plant, as novel as modulators of TLR-4 signaling, highlighting their mechanisms of action and potential clinical applications. In the present study, 18 phytocompounds isolated from the rhizome of , were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach.

Results

The compounds exhibited binding affinities ranging from -4.087 to -8.93 with the TLR-4 protein due to the formation of multiple intermolecular interactions. Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, methyl ester (compound 7) exhibited exceptional binding energy (-8.93 kcal/mol), indicating strong affinity for the TLR-4 protein. Additionally, compound 7 displayed favorable ADMET properties, suggesting promising drug development potential. Molecular dynamics simulations confirmed the stability of the compound 7-TLR4 complex, further supporting its ability to modulate TLR-4 signaling.

Conclusion

These findings highlight the therapeutic potential of phytocompounds, particularly compound 7, as potent anti-inflammatory modulators. Further research is warranted to validate their anti-inflammatory and neuroprotective effects in pre-clinical models, paving the way for their development as novel therapeutic agents for inflammatory diseases.

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2025-06-20

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Anti-inflammatory Potential of Costus speciosus rhizome Bioactive Phytochemicals: A Combined GC-MS and Computational Approach Targeting TLR-4 Signaling
Curr. Computeraided Drug Des. 21, 285 (2025); https://doi.org/10.2174/0115734099309926241007055607
/content/journals/cad/10.2174/0115734099309926241007055607
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  • Article Type:     Research Article
Keyword(s): ADMET; Alzheimer's disease; Costus speciosus; GC-MS analysis; inflammation; molecular docking; molecular dynamics simulations; toll-like receptor 4

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