Pharmacogenomic Regulation of the NF-kB–Nrf2 Axis by Curcumin: A Precision Molecular Approach to Inflammation and Oxidative Stress
DOI:
https://doi.org/10.53366/jimki.v12i2.1050Keywords:
Curcumin, NF-kB, Nrf2Abstract
Introduction: Chronic inflammation and oxidative stress are major mechanisms in degenerative diseases, including cancer, diabetes, and cardiovascular disorders. The NF-kB and Nrf2 pathways play a role in maintaining redox balance and inflammatory response. Curcumin, the main bioactive compound of Curcuma longa L., can simultaneously modulate both pathways through pharmacogenomic mechanisms influenced by individual genetic variations.
Method: This study used the Systematic Literature Review method in accordance with the PRISMA 2020 guidelines. Searches were conducted in PubMed, Scopus, ScienceDirect, and Google Scholar until October 2025 using the keywords “Curcumin,” “NF-kB,” “Nrf2,” “Oxidative Stress,” and “Pharmacogenomics.” Studies assessing the molecular modulation of NF-kB/Nrf2 by curcumin and gene-dependent effects were included.
Results and Discussion: A total of 31 studies met the inclusion criteria, including in vitro, in vivo, in silico, and clinical studies. Curcumin suppressed NF-kB activation and activated Nrf2/HO-1, thereby reducing ROS and proinflammatory cytokines. Variations in the ERCC5 rs751402 gene, as well as the expression of SLC7A11 and ATAD3A/B, influenced the cellular response to curcumin. In silico and network pharmacology analyses revealed multigenic targets related to inflammation and oxidative stress. Nanoformulations enhance bioavailability and clinical immune response.
Conclusion: Curcumin acts as a dual-regulator pharmacogenomic agent that balances the NF-kB and Nrf2 pathways, reducing inflammation and oxidative stress in a gene-dependent manner. These findings support its potential as a natural biomolecule for the development of precision therapies for chronic diseases involving inflammation and oxidative stress.
Keywords: Curcumin, NF-kB, Nrf2, Oxidative Stress, Pharmacogenomics
References
1. Shahcheraghi SH, Salemi F, Peirovi N, Ayatollahi J, Alam W, Khan H, et al. Nrf2 regulation by curcumin: molecular aspects for therapeutic prospects. Molecules. 2022;27:1-20.
2. Pongsavee M. Effects of ERCC5 rs751402 polymorphism on oxidative stress and the impact of curcumin on catalase activity in breast carcinogenesis. Asian Pac J Cancer Prev. 2022;23:2065–70.
3. Wei J, Wang X, Dong Y, Zhong X, Ren X, Song R, et al. Curcumae rhizoma - combined with sparganii rhizoma in the treatment of liver cancer : chemical analysis using UPLC-LTQ-Orbitrap MSn , network analysis , and experimental assessment. Front Pharmacol. 2022;13:1–22.
4. Paul M, Alekhya AV, Krishnamurthy L. How effective is curcumin in prevention of cancer. Int J Pharm Sci Rev Res. 2021;69:1–18.
5. Ashrafizadeh M, Zarrabi A, Hushmandi K, Zarrin V, Moghadam ER, Hashemi F, et al. Toward regulatory effects of curcumin on transforming growth factor-beta across different diseases : a review. Front Pharmacol. 2020;11:1-24.
6. Gao W, Guo L, Yang Y, Wang Y, Xia S, Gong H, et al. Dissecting the crosstalk between Nrf2 and NF-κB response pathways in drug-induced toxicity. Front Cell Dev Biol. 2022;9:1–21.
7. Maboudian M, Amjad E, Asnaashari S, Dastmalchi S, Sokouti B, Javadzadeh Y. Evaluation of the effects of curcumin on chronic obstructive pulmonary disease with a bio‑computational approach. Egypt J Med Hum Genet. 2024;25:1-18. Available from: https://doi.org/10.1186/s43042-024-00486-6
8. Dai C, Li M, Liu Y, Tran DH, Jiang H, Tang S, et al. Involvement of the inhibition of mitochondrial apoptotic , p53, NF-κB pathways and the activation of Nrf2 / HO-1 pathway in the protective effects of curcumin against copper sulfate-induced nephrotoxicity in mice. Ecotoxicol Environ Saf. 2023;249:1-10.
9. Karimi A, Pourreza S, Vajdi M, Mahmoodpoor A, Sanaie S, Karimi M, et al. Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients : A randomized, double-blind, and placebo-controlled trial. Front Nutr. 2022;9:1–12.
10. Sankaran H, Negi S, Mcshane LM, Zhao Y, Krushkal J. Pharmacogenomics of in vitro response of the NCI‑60 cancer cell line panel to Indian natural products. BMC Cancer. 2022;22:1–22. Available from: https://doi.org/10.1186/s12885-022-09580-7
11. Lebda MA, Elmassry IH, Taha NM, Elfeky MS. Nanocurcumin alleviate inflammation and oxidative stress in LPS-induced mastitis model via activation of Nrf2 and suppressing TLR4 mediated NF-κB and HMGB1 signaling pathways. Research Square. 2021:1–20.
12. Li W, Jiang L, Lu X, Liu X, Ling M. Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway. BMC Complement Med Ther. 2021;1:1–10.
13. Dai C, Tian E, Hao Z, Tang S, Wang Z, Sharma G, et al. Aflatoxin B1 toxicity and protective effects of curcumin : molecular mechanisms and clinical implications. Antioxidants. 2022;11:1-23.
14. Lee MK, Kim HD, Lee SH, Lee JH. Curcumin Ameliorates Particulate Matter-Induced Pulmonary Injury through Bimodal Regulation of Macrophage Inflammation via NF- κ B and Nrf2. Int J Mol Sci. 2023;24:1-14.
15. Mondal D, Narwani D, Notta S, Ghaffar D, Mardhekar N, Quadri SSA. Oxidative stress and redox signaling in CRPC progression : therapeutic potential of clinically-tested Nrf2-activators. Cancer Drug Resist. 2021;4:96–124.
16. Thiruvengadam M, Venkidasamy B, Subramanian U, Samynathan R, Shariati MA, Rebezov M, et al. Bioactive compounds in oxidative stress-mediated diseases : targeting the NRF2/ARE signaling pathway and epigenetic regulation. Antioxidants. 2021;10:1–24.
17. Duan C, Wang H, Jiao D, Geng Y, Wu Q, Yan H, et al. Curcumin restrains oxidative stress of after intracerebral hemorrhage in rat by activating the Nrf2/HO-1 pathway. Front Pharmacol. 2022;13:1–15.
18. Sarawi WS, Alhusaini AM, Fadda LM, Alomar HA, Albaker AB, Alghibiwi HK, et al. Nano-curcumin prevents copper reproductive toxicity by attenuating oxidative stress and inflammation and improving Nrf2/HO-1 Signaling and pituitary-gonadal axis in male rats. Toxics. 2022;10:1-16.
19. Yin ZH, Tan WH, Jiang YL. Exploration of the molecular mechanism of curcuma aromatica salisb's anticolorectal cancer activity via the integrative approach of network pharmacology and experimental validation. ACS Omega. 2024;9:21426-39.
20. Jin S, Yang H, Jiao Y, Pang Q, Wang Y, Wang M, et al. Dietary curcumin alleviated acute ileum damage of ducks (anas platyrhynchos) induced by AFB1 through regulating Nrf2-ARE and NF-kB signaling pathways. Foods. 2021;10:1-15.
21. Mahmoudi A, Atkin SL, Nikiforov NG, Sahebkar A. Therapeutic role of curcumin in diabetes : an analysis based on bioinformatic findings. Nutrients. 2022;14:1-18.
22. Oshevire DB, Mustapha A, Alozieuwa BU, Badeggi HH, Ismail A, Hassan ON, et al. In-silico investigation of curcumin drug-likeness, gene-targets and prognostic relevance of the targets in panels of human cancer cohorts. GCS Biol Pharm Sci. 2021;14:37-46.
23. Stasi LCD. Natural coumarin derivatives activating Nrf2 signaling pathway as lead compounds for the design and synthesis of intestinal anti-inflammatory drugs. Pharmaceuticals. 2023;16:1-26.
24. Cui J, Li H, Zhang T, Lin F, Chen M, Zhang G, et al. Research progress on the mechanism of curcumin anti-oxidative stress based on signaling pathway. Front Pharmacol. 2025;16:1–17.
25. Sharifi-Rad J, Rayess YE, Rizk AA, Sadaka C, Zgheib R, Zam W, et al. Turmeric and its major compound curcumin on health : bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol. 2020;11:1–24.
26. Fagiani F, Catanzaro M, Buoso E, Basagni F, Marino DD, Raniolo S, et al. Targeting cytokine release through the differential modulation of Nrf2 and NF-kB pathways by electrophilic/ non-electrophilic compounds. Front Pharmacol. 2020;11:1–14.
27. Liu S, Li Q, Liu F, Cao H, Liu J, Shan J, et al. Uncovering the mechanism of curcuma in the treatment of ulcerative colitis based on network pharmacology, molecular docking technology, and experiment verification. Evid Based Complement Alternat Med. 2021;2021:1-14.
28. Yuandani, Jantan I, Rohani AS, Sumantri IB. Immunomodulatory effects and mechanisms of curcuma species and their bioactive compounds : a review. Front Pharmacol. 2021;12:1–26.
29. Anunciacao TAD, Garcez LS, Pereira EM, Queiroz VADO, Costa PRDF, Oliveira LPMD. Curcumin supplementation in the treatment of patients with cancer : a systematic review. Braz J Pharm Sci. 2021;57:1–14.
30. Ferreira AS, Macedo C, Silva AM, Delerue-matos C, Costa P, Rodrigues F. Natural products for the prevention and treatment of oral mucositis-a review. Int J Mol Sci. 2022;23:1-31.
31. Islam MM, Sultana N, Liu C, Mao A, Katsube T, Wang B. Impact of dietary ingredients on radioprotection and radiosensitization : a comprehensive review. Ann Med. 2024;56:1-23. Available from: https://doi.org/10.1080/07853890.2024.2396558
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Questa Soundri Alisya, Khairunnisa, Abdullah
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.