Molecular Pharmacokinetics and Structural Docking of Phenolic Acids for Targeting NF-κB Pathway Components in Inflammation and Fibrosis: A Computational Approach Toward Therapeutic Discovery

Notice

This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2025 | Volume : 03 | Issue : 01 | Page : –
    By

    Anamika Jayprasad,

  1. Student, Department of Bioscisnces, MES MK Mackar Pillay College For Advanced Studies, Aluva, Kerala, India

Abstract

Inflammation and Fibrosis are critical pathological processes associated with various chronic diseases, often mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. This study investigates the therapeutic potential of phenolic acids as modulators of the NF-κB pathway, aiming to identify novel ligands that can effectively interact with key components of this signaling cascade. A comprehensive computational approach was employed, utilizing molecular docking, pharmacological screening, and post-docking analysis to evaluate the binding interactions of selected phenolic acids with NF-κB and NEMO proteins. Ligands were sourced from PhytoHub and PubChem, and pharmacokinetic properties were assessed using the Swiss ADME tool, focusing on Lipinski’s rule, gastrointestinal absorption, bioavailability, and potential assay interference (PAINS) and toxicity concerns (BRENK). The docking studies revealed that compounds such as Vanilloylglycine (-6.1 kcal/mol), 2,4,6-Trihydroxybenzoic acid (-5.9 kcal/mol), and Syringic acid (-5.9 kcal/mol) exhibited strong binding affinities with NF-κB, while Hippuric Acid (-6.2 kcal/mol), Vanilloylglycine (-6.2 kcal/mol), and 4-Hydroxybenzoic acid (-6.1 kcal/mol) showed promising interactions with NEMO. The post-docking analysis showed strong interactions, such as hydrogen bonds, hydrophobic interactions, and electrostatic forces, indicating a strong and stable binding process. The pharmacological evaluations of these compounds demonstrated favorable properties, such as appropriate molecular weight, solubility, and lipophilicity, positioning them as promising candidates for further development. These findings suggest that phenolic acids could serve as effective modulators of the NF-κB pathway, potentially mitigating inflammation and fibrosis. However, experiments are needed to verify these computer-based predictions. The study’s limitations include the need for in vitro and in vivo testing, as well as optimization of the compounds for improved pharmacokinetic profiles. This research underscores the potential of phenolic acids as therapeutic agents in chronic disease management, with promising future perspectives for drug development.

Keywords: Fibrosis, Inflammation, NF-κB, NEMO, Swiss ADME, Molecular Docking

[This article belongs to International Journal of Cell Biology and Cellular Functions ]

How to cite this article:
Anamika Jayprasad. Molecular Pharmacokinetics and Structural Docking of Phenolic Acids for Targeting NF-κB Pathway Components in Inflammation and Fibrosis: A Computational Approach Toward Therapeutic Discovery. International Journal of Cell Biology and Cellular Functions. 2025; 03(01):-.
How to cite this URL:
Anamika Jayprasad. Molecular Pharmacokinetics and Structural Docking of Phenolic Acids for Targeting NF-κB Pathway Components in Inflammation and Fibrosis: A Computational Approach Toward Therapeutic Discovery. International Journal of Cell Biology and Cellular Functions. 2025; 03(01):-. Available from: https://journals.stmjournals.com/ijcbcf/article=2025/view=203251



References

1. Chikowe M, Bafor E, Maredza A, et al. GC–MS analysis, molecular docking, and pharmacokinetic studies of Multidentia crassa extracts’ compounds for analgesic and anti-inflammatory activities in dentistry. Sci Rep. 2024;14(1):1876.

2. Ekowati Y, Nugroho H, Mardianingsih A, et al. Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach. ACS Omega. 2023;8(49):46851-46868.

3. Gan C, Zhang Y, Li Y, et al. Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ. J Inflamm. 2023;20(1):8.

4. Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):1-9.

5. Johns Hopkins Medicine. Cystic fibrosis. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/cystic-fibrosis

6. Yu X, Guo M, Wang S, et al. Pharmacological effects of polyphenol phytochemicals on the intestinal inflammation via targeting TLR4/NF-κB signaling pathway. Int J Mol Sci. 2022;23(13):6939.

7. Cystic Fibrosis Trust. What is cystic fibrosis? Available from: https://www.cysticfibrosis.org.uk/what-is-cystic-fibrosis

8. Guan Y, Zheng J, Wang C, et al. Network pharmacology and molecular docking suggest the mechanism for biological activity of rosmarinic acid. Evid Based Complement Alternat Med. 2021;2021:5190808.

9. Khan S, Kumar V, Sahu K, et al. Anti-inflammatory and anti-rheumatic potential of selective plant compounds by targeting TLR-4/AP-1 signaling: A comprehensive molecular docking and simulation approaches. Molecules. 2022;27(13):4319.

10. Rahman S, Hoque M, Hossain M, et al. An in-silico identification of potential flavonoids against kidney fibrosis targeting TGFβR-1. Life. 2022;12(11):1764.

11. Moynagh PN. The NF-κB pathway. J Cell Sci. 2005;118(20):4589-4592.

12. Ramadoss A, Saraswat D, Rani A, et al. Potency of anti-fibrotic herbs on fibrogenesis: A theoretical evaluation. Phytomedicine Plus. 2023;3(4):100496.

13. Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2006;173(5):475-482.

14. National Heart, Lung, and Blood Institute. Cystic fibrosis. Available from: https://www.nhlbi.nih.gov/health/cystic-fibrosis

15. Kumar R, Mehta K, Singh S, et al. Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnol Rep. 2019;24:e00370.

16. Gross GG. Phenolic acids. In: Conn EE, editor. Secondary Plant Products. The Biochemistry of Plants—A Comprehensive Treatise. 1981;301-316.

17. Stern RC. The diagnosis of cystic fibrosis. N Engl J Med. 1997;336(7):487-491.

18. Ong T, Tan Y, Li F, et al. Cystic fibrosis: A review. JAMA. 2023;329(21):1859-1871.

19. De Boeck K, Amaral MD, Louros K, et al. Progress in therapies for cystic fibrosis. Lancet Respir Med. 2016;4(8):662-674.

20. Yamamoto M, Gaynor RB. Role of the NF-kB pathway in the pathogenesis of human disease states. Curr Mol Med. 2001;1(3):287-296.

21. Lafay S, Nardello-Rataj V, Vercauteren J. Bioavailability of phenolic acids. Phytochem Rev. 2008;7:301-311.

22. Robbins RJ, Wooten J, Hunter H, et al. Phenolic acids in foods: an overview of analytical methodology. J Agric Food Chem. 2003;51(10):2866-2887.

23. Senftleben U, Cao Y, Xiao G, et al. The Ikk/nf-κb pathway. Crit Care Med. 2002;30(1):S18-S26.

24. Lawrence T. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651.

25. Bell SC, Elborn JS, Drevinek P, et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med. 2020;8(1):65-124.

Regular Issue Subscription Original Research
Volume 03
Issue 01
Received 27/02/2025
Accepted 08/03/2025
Published 10/03/2025
Publication Time 11 Days
Total Visits: 27


My IP

PlumX Metrics