Abstract
Inflammation is a complex biological response driven by excessive activation of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), which play pivotal roles in chronic inflammatory diseases. Given the safety and wide clinical use of atorvastatin, this study aimed to explore its potential repurposing as an anti-inflammatory agent through the inhibition of these cytokines. Molecular docking was performed to predict the binding affinity and interaction profile of atorvastatin with TNF-α, IL-1β, and IL-6, followed by 200 ns molecular dynamics (MD) simulations, principal component analysis (PCA), and energy calculations to evaluate the stability and energetics of the complexes. Furthermore, the anti-inflammatory effects of atorvastatin (5–20 µM) were evaluated in LPS-stimulated RAW 264.7 macrophages using MTT cytotoxicity, cytokine assays (TNF-α, IL-6, IL-1β), and nitric oxide quantification. Docking study revealed strong binding affinity toward TNF-α (− 7.9 kcal/mol) through hydrogen bonding, supported by stable MD trajectories. The MM-GBSA binding energy (− 72.90 ± 4.38 kcal/mol) confirmed a favorable and stable interaction predominantly driven by hydrophobic and van der Waals forces. In -vitro study revealed, that atorvastatin showed no cytotoxicity and produced a strong dose-dependent inhibition of TNF-α, IL-6, IL-1β, and nitric oxide levels, with maximal anti-inflammatory activity observed at 20 µM. These findings suggest that atorvastatin may directly inhibit TNF-α and related cytokines, thereby modulating NF-κB–mediated inflammatory signaling. This study provides molecular-level insight supporting the repurposing of atorvastatin as a promising multi-target anti-inflammatory therapeutic.
Data availability
The data will be available on request from corresponding author.
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Acknowledgements
We thank King Faisal University, Al-Ahsa, Saudi Arabia, for support and this research was funded by the General Directorate of Scientific Research & Innovation, Dar Al Uloom University, through the Scientific Publishing.
Funding
This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Grant No: KFU260626].
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Krishna Swaroop: Conceptualization, Data curation, Methodology, Validation, Writing—original draft. Renukaradhya M., Sadik Shaik, and Ravi Chander Thatipelli: Data curation, Investigation, Methodology. Saeed Shokri: Formal analysis, Methodology. Hamid Rezaee Jam: Methodology, Investigation. K.V. Swathi Krishna, Sibghatullah Muhammad Ali Sangi, and Monirul Islam: Methodology, Resources, and Data curation. Girish Meravanige, Nagaraja Sreeharsha, and Muhammad Shahzad Chohan: Formal analysis, Data curation, Writing—review & editing. Shankar Thapa: Conceptualization, Supervision, Software, Writing—review & editing. Akinpelumi Akin-Adewumi: Resources, Methodology. Ayomide Victor Atoki: Writing—review & editing.
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Swaroop, K., M., R., Shaik, S. et al. Evaluation of the anti-inflammatory potential of atorvastatin targeting TNF-α, IL-6, and IL-1β using integrated in vitro and in silico approaches. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39082-6
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DOI: https://doi.org/10.1038/s41598-026-39082-6
