Lemongrass Bioactive Compounds in Modulating NF-κB and MAPK Inflammatory Signaling Pathways: Molecular Mechanisms, Experimental Evidence, and Therapeutic Perspectives
Main Article Content
Keywords
Cymbopogon citratus; Lemongrass; Bioactive compounds; Inflammation; NF-κB; MAPK; Citral; Phytochemicals; Oxidative stress; Anti-inflammatory activity.
Abstract
Inflammation is a tightly regulated biological defense mechanism that protects the body against microbial invasion, physical injury, and other harmful stimuli while promoting tissue repair and restoration of homeostasis. Although this response is essential for maintaining physiological balance, prolonged or dysregulated inflammation contributes to the onset and progression of numerous chronic disorders. Among the key molecular regulators of inflammatory responses, the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways play central roles by controlling the expression of genes encoding pro-inflammatory mediators. Consequently, these pathways have become important therapeutic targets for the development of safer and more effective anti-inflammatory interventions.
Cymbopogon citratus (lemongrass) is a widely used medicinal and aromatic plant recognized for its rich phytochemical composition and diverse pharmacological properties. This review comprehensively examines the phytochemistry of C. citratus and discusses the molecular mechanisms through which its bioactive constituents regulate inflammatory signaling pathways. Particular attention is given to major phytochemicals, including citral, chlorogenic acid, flavonoids, and geraniol, which have demonstrated significant anti-inflammatory activity through modulation of NF-κB and MAPK signaling.
Evidence obtained from phytochemical investigations, cell-based experiments, and animal studies indicates that lemongrass-derived bioactive compounds suppress inflammatory responses by reducing the production of pro-inflammatory mediators, limiting oxidative stress, and regulating multiple intracellular signaling pathways. The available findings further suggest that these compounds exert complementary and multitarget actions, thereby enhancing their overall therapeutic potential against inflammation-associated diseases.
Despite encouraging experimental evidence, several challenges remain before the clinical application of lemongrass-derived therapeutics can be fully realized. These include the need for standardized phytochemical preparations, improved understanding of pharmacokinetic behavior, optimization of dosage, and well-designed clinical trials to validate efficacy and safety in humans. Addressing these limitations will strengthen the scientific basis for the development of lemongrass-based anti-inflammatory agents and support their future therapeutic application.
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2. Arthur, J. S. C., & Ley, S. C. (2013). Mitogen-activated protein kinases in innate immunity. Nature Reviews Immunology, 13(9), 679–692. https://doi.org/10.1038/nri3495
3. Avoseh, O., Oyedeji, O., Rungqu, P., Nkeh-Chungag, B., & Oyedeji, A. (2015). Cymbopogon species; ethnopharmacology, phytochemistry and the pharmacological importance. Molecules, 20(5), 7438–7453. https://doi.org/10.3390/molecules20057438
4. Bachiega, T. F., & Sforcin, J. M. (2011). Lemongrass and citral effect on cytokine production by murine macrophages. Journal of Ethnopharmacology, 137(1), 909–913. https://doi.org/10.1016/j.jep.2011.07.021
5. Bao, X. L., Yuan, H. H., Wang, C. Z., Fan, W., & Lan, M. B. (2015). Polysaccharides from Cymbopogon citratus with antitumor and immunomodulatory activity. Pharmaceutical Biology, 53(1), 117–124. https://doi.org/10.3109/13880209.2014.911921
6. Boukhatem, M. N., Ferhat, M. A., Kameli, A., Saidi, F., & Kebir, H. T. (2014). Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drug. Libyan Journal of Medicine, 9, 25431. https://doi.org/10.3402/ljm.v9.25431
7. Campos, C. A., Lima, B. S., Trindade, G. G. G., Souza, E. P. B. S., Mota, D. S. A., Heimfarth, L., Quintans, J. S. S., Quintans-Júnior, L. J., Sussuchi, E. M., Sarmento, V. H. V., Carvalho, F. M. S., Marreto, R. N., Costa, R. M., Nunes, R. S., Araújo, A. A. S., Shanmugam, S., & Thangaraj, P. (2019). Anti-hyperalgesic and anti-inflammatory effects of citral with β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion complexes in animal models. Life Sciences, 229, 139–148. https://doi.org/10.1016/j.lfs.2019.05.026
8. Chen, J., & Chen, Z. J. (2013). Regulation of NF-κB by ubiquitination. Current Opinion in Immunology, 25(1), 4–12. https://doi.org/10.1016/j.coi.2012.12.005
9. Cho, J. Y., Baik, K. U., Jung, J. H., & Park, M. H. (2003). In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. European Journal of Pharmacology, 398, 399–407.
10. Costa, G., Ferreira, J. P. B., Vitorino, C., Pina, M. E., Sousa, J. J. S., Figueiredo, I. V., & Batista, M. T. (2016). Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents. Journal of Ethnopharmacology, 178, 222–228. https://doi.org/10.1016/j.jep.2015.12.016
11. Figueirinha, A., Paranhos, A., Pérez-Alonso, J. J., Santos-Buelga, C., & Batista, M. T. (2008). Cymbopogon citratus leaves: Characterization of flavonoids by HPLC–PDA–ESI/MS/MS and an approach to their potential as a source of bioactive polyphenols. Food Chemistry, 110(3), 718–728. https://doi.org/10.1016/j.foodchem.2008.02.045
12. Francisco, V., Figueirinha, A., Neves, B. M., García-Rodríguez, C., Lopes, M. C., Cruz, M. T., & Batista, M. T. (2011). Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages. Journal of Ethnopharmacology, 133(2), 818–827. https://doi.org/10.1016/j.jep.2010.11.018
13. Francisco, V., Figueirinha, A., Costa, G., Lopes, M. C., García-Rodríguez, C., Cruz, M. T., & Batista, M. T. (2011). Anti-inflammatory properties of polyphenols from Cymbopogon citratus by inhibition of NF-κB pathway. Planta Medica, 77, 1158. https://doi.org/10.1055/s-0031-1282839
14. Francisco, V., Costa, G., Figueirinha, A., Marques, C., Pereira, P., Neves, B. M., Lopes, M. C., García-Rodríguez, C., Cruz, M. T., & Batista, M. T. (2013). Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: Contribution of chlorogenic acid. Journal of Ethnopharmacology, 148(1), 126–134. https://doi.org/10.1016/j.jep.2013.03.077
15. Ganeshan, K., & Chawla, A. (2014). Metabolic regulation of immune responses. Annual Review of Immunology, 32, 609–634. https://doi.org/10.1146/annurev-immunol-032713-120236
16. García-Lafuente, A., Guillamón, E., Villares, A., Rostagno, M. A., & Martínez, J. A. (2009). Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflammation Research, 58(9), 537–552. https://doi.org/10.1007/s00011-009-0037-3
17. Guimarães, L. G. L., Cardoso, M. G., Sousa, P. E., Andrade, J., & Vieira, S. S. (2011). Antioxidant and anti-inflammatory activities of essential oils from Cymbopogon species. Industrial Crops and Products, 33(2), 419–424.
18. Han, X., & Parker, T. L. (2017). Anti-inflammatory activity of essential oils from Cymbopogon species. Journal of Functional Foods, 35, 635–641. https://doi.org/10.1016/j.jff.2017.06.014
19. Heinrich, M., Barnes, J., Gibbons, S., & Williamson, E. M. (2012). Fundamentals of Pharmacognosy and Phytotherapy (2nd ed.). Elsevier.
20. Hussain, A. I., Anwar, F., Sherazi, S. T. H., & Przybylski, R. (2008). Chemical composition, antioxidant and antimicrobial activities of basil (Ocimum basilicum) essential oils depends on seasonal variations. Food Chemistry, 108(3), 986–995.
21. Kim, E. K., & Choi, E. J. (2010). Pathological roles of MAPK signaling pathways in human diseases. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1802(4), 396–405. https://doi.org/10.1016/j.bbadis.2009.12.009
22. Kim, H. P., Son, K. H., Chang, H. W., & Kang, S. S. (2004). Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of Pharmacological Sciences, 96(3), 229–245. https://doi.org/10.1254/jphs.CRJ04003X
23. Lawrence, T. (2009). The nuclear factor NF-κB pathway in inflammation. Cold Spring Harbor Perspectives in Biology, 1(6), a001651. https://doi.org/10.1101/cshperspect.a001651
24. Lee, I. T., & Yang, C. M. (2013). Role of NADPH oxidase/ROS in pro-inflammatory mediators and MAPK signaling. Redox Biology, 1(1), 1–11. https://doi.org/10.1016/j.redox.2013.01.010
25. Li, Q., & Verma, I. M. (2002). NF-κB regulation in the immune system. Nature Reviews Immunology, 2(10), 725–734. https://doi.org/10.1038/nri910
26. Libby, P. (2007). Inflammatory mechanisms: The molecular basis of inflammation and disease. Nutrition Reviews, 65(12 Pt 2), S140–S146. https://doi.org/10.1111/j.1753-4887.2007.tb00352.x
27. Liao, J. C., Deng, J. S., Chiu, C. S., Hou, W. C., Huang, S. S., Shie, P. H., Huang, G. J. (2015). Anti-inflammatory activities of Cinnamomum cassia constituents through suppression of NF-κB and MAPK signaling pathways. Journal of Agricultural and Food Chemistry, 63(15), 429–437.
28. Liu, T., Zhang, L., Joo, D., & Sun, S. C. (2017). NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy, 2, 17023. https://doi.org/10.1038/sigtrans.2017.23
29. López-Lázaro, M. (2009). Distribution and biological activities of the flavonoid luteolin. Mini-Reviews in Medicinal Chemistry, 9(1), 31–59. https://doi.org/10.2174/138955709787001712
30. Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454(7203), 428–435. https://doi.org/10.1038/nature07201
31. Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65(9), 732–741. https://doi.org/10.1016/j.biopsych.2008.11.029
32. Naik, M. I., Fomda, B. A., Jaykumar, E., & Bhat, J. A. (2010). Antibacterial activity of lemongrass (Cymbopogon citratus) oil against some selected pathogenic bacteria. Asian Pacific Journal of Tropical Medicine, 3(7), 535–538. https://doi.org/10.1016/S1995-7645(10)60129-0
33. Nathan, C. (2002). Points of control in inflammation. Nature, 420(6917), 846–852. https://doi.org/10.1038/nature01320
34. Nathan, C., & Ding, A. (2010). Nonresolving inflammation. Cell, 140(6), 871–882. https://doi.org/10.1016/j.cell.2010.02.029
35. Negrelle, R. R. B., & Gomes, E. C. (2007). Cymbopogon citratus (DC.) Stapf: Chemical composition and biological activities. Revista Brasileira de Plantas Medicinais, 9(1), 80–92. (Worldwide Journals)
36. Pan, M.-H., Lai, C.-S., & Ho, C.-T. (2010). Anti-inflammatory activity of natural dietary flavonoids. Food & Function, 1(1), 15–31. https://doi.org/10.1039/C0FO00103A
37. Pan, M.-H., Lai, C.-S., Wang, Y.-J., & Ho, C.-T. (2014). Acquired resilience to oxidative stress and inflammation: The role of phytochemicals. Journal of Agricultural and Food Chemistry, 62(30), 7406–7416. https://doi.org/10.1021/jf501362x
38. Park, E. J., & Pezzuto, J. M. (2002). Botanicals in cancer chemoprevention. Cancer and Metastasis Reviews, 21(3–4), 231–255. https://doi.org/10.1023/A:1021254725842
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Published
Mar 22, 2022
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How to Cite
Siddhartha Mehrotra, & Dr. Gauri Saxena. (2022). Lemongrass Bioactive Compounds in Modulating NF-κB and MAPK Inflammatory Signaling Pathways: Molecular Mechanisms, Experimental Evidence, and Therapeutic Perspectives. Journal of Population Therapeutics and Clinical Pharmacology, 29(01), 1001-1047. https://doi.org/10.69980/b8sdy555
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Author Biographies
Siddhartha Mehrotra
Research Scholar, Department of Botany, University of Lucknow, 0009-0009-1514-4495
Dr. Gauri Saxena
Professor, Department of Botany, University of Lucknow, 0000-0003-2235-2755
How to Cite
Siddhartha Mehrotra, & Dr. Gauri Saxena. (2022). Lemongrass Bioactive Compounds in Modulating NF-κB and MAPK Inflammatory Signaling Pathways: Molecular Mechanisms, Experimental Evidence, and Therapeutic Perspectives. Journal of Population Therapeutics and Clinical Pharmacology, 29(01), 1001-1047. https://doi.org/10.69980/b8sdy555
