Acta Natura et Scientia
ISSN (Online): 2718-0638

Review article    |    Open Access
Acta Natura et Scientia 2026, Vol. 7(1) 18-33

Differential Immunomodulatory and Antioxidative Mechanisms of Lycopene and Coumarin Derivatives in Nigerian Medicinal Plants: A Comprehensive Meta-Analysis With Therapeutic Implications

Mathew Folaranmi Olaniyan, Odekunle Bola Odegbemi, Moyinoluwa Elizabeth Babatunde , Godfrey Innocent Iyare

pp. 18 - 33   |  DOI: https://doi.org/10.61326/actanatsci.v7i1.390

Publish Date: March 06, 2026  |   Single/Total View: 0/0   |   Single/Total Download: 0/0

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Abstract

Nigeria’s biodiverse flora represents an untapped reservoir of therapeutically active phytochemicals. Lycopene and coumarin compounds, prevalent in traditional Nigerian medicinal plants, demonstrate distinct but potentially synergistic biological activities that warrant systematic investigation. To conduct a comprehensive meta-analytical comparison of immunomodulatory and antioxidative properties of lycopene and coumarin derivatives extracted from Nigerian medicinal plants, elucidating their molecular mechanisms and therapeutic potential. We performed systematic searches across five databases (PubMed, Scopus, AJOL, Web of Science, and Cochrane Library) for studies published between January 2000 and April 2024. Inclusion criteria encompassed peer-reviewed studies evaluating lycopene or coumarin compounds from Nigerian plant species with quantitative immunological or antioxidant outcomes. Meta-analyses employed random-effects models with heterogeneity assessment via I² statistics. Molecular pathway analysis was conducted using bioinformatics approaches. From 148 initially identified records, 38 studies (n=4,247 subjects across human, animal, and in vitro models) met inclusion criteria. Lycopene demonstrated superior antioxidant capacity with significant reductions in malondialdehyde (pooled mean difference [PMD]: -1.45 μmol/L, 95% CI: -2.10 to -0.82, p<0.001) and enhanced superoxide dismutase activity (PMD: +8.2 U/mL, 95% CI: 5.4 to 11.0, p<0.001) (3,4). Coumarin compounds exhibited stronger immunomodulatory effects, significantly reducing tumor necrosis factor-α (PMD: -12.3 pg/mL, 95% CI: -18.2 to -6.4, p<0.001) and elevating interleukin-10 (PMD: +2.4 pg/mL, 95% CI: 1.0 to 3.8, p=0.002) (5,6). Molecular pathway analysis revealed lycopene primarily activates Nrf2-mediated antioxidant responses, while coumarin modulates NF-κB signaling cascades. Lycopene and coumarin compounds from Nigerian medicinal plants demonstrate complementary therapeutic mechanisms. Lycopene excels in oxidative stress mitigation through direct radical scavenging and enzymatic antioxidant enhancement, while coumarin compounds provide superior immunoregulation via cytokine modulation. These findings support the development of standardized phytotherapeutic formulations and highlight the potential for combination therapies in managing inflammatory and oxidative stress-related disorders.

Keywords: Lycopene, Coumarin, Immunomodulation, Nigerian Medicinal Plants, Antioxidant mechanisms

How to Cite this Article?

APA 7th edition
Olaniyan, M.F., Odegbemi, O.B., Babatunde, M.E., & Iyare, G.I. (2026). Differential Immunomodulatory and Antioxidative Mechanisms of Lycopene and Coumarin Derivatives in Nigerian Medicinal Plants: A Comprehensive Meta-Analysis With Therapeutic Implications. Acta Natura et Scientia, 7(1), 18-33. https://doi.org/10.61326/actanatsci.v7i1.390

Harvard
Olaniyan, M., Odegbemi, O., Babatunde, M. and Iyare, G. (2026). Differential Immunomodulatory and Antioxidative Mechanisms of Lycopene and Coumarin Derivatives in Nigerian Medicinal Plants: A Comprehensive Meta-Analysis With Therapeutic Implications. Acta Natura et Scientia, 7(1), pp. 18-33.

Chicago 16th edition
Olaniyan, Mathew Folaranmi, Odekunle Bola Odegbemi, Moyinoluwa Elizabeth Babatunde and Godfrey Innocent Iyare (2026). "Differential Immunomodulatory and Antioxidative Mechanisms of Lycopene and Coumarin Derivatives in Nigerian Medicinal Plants: A Comprehensive Meta-Analysis With Therapeutic Implications". Acta Natura et Scientia 7 (1):18-33. https://doi.org/10.61326/actanatsci.v7i1.390

References
  1. Abarikwu, S. O. (2014). Anti-inflammatory effects of kolaviron modulate the expressions of inflammatory marker genes, inhibit transcription factors ERK1/2, p-JNK, NF-κB, and activate Akt expressions in the 93RS2 Sertoli cell lines. Molecular and Cellular Biochemistry, 401, 197–208. https://doi.org/10.1007/s11010-014-2307-9 [Google Scholar] [Crossref] 
  2. Adefegha, S. A., & Oboh, G. (2012). Acetylcholinesterase (AChE) inhibitory activity, antioxidant properties and phenolic composition of two Aframomum species. Journal of Basic and Clinical Physiology and Pharmacology, 23(4), 153–161. https://doi.org/10.1515/jbcpp-2012-0029 [Google Scholar] [Crossref] 
  3. Akinmoladun, A. C., Obuotor, E. M., & Farombi, E. O. (2010). Evaluation of antioxidant and free radical scavenging capacities of some Nigerian indigenous medicinal plants. Journal of Medicinal Food, 13(2), 444-451. https://doi.org/10.1089/jmf.2008.0292 [Google Scholar] [Crossref] 
  4. Amadi, S. W., Zhang, Y., & Wu, G. (2016). Research progress in phytochemistry and biology of Aframomum species. Pharmaceutical Biology, 54(11), 2761–2770. https://doi.org/10.3109/13880209.2016.1173068 [Google Scholar] [Crossref] 
  5. Anyanwu, M. U., & Okoye, R. C. (2017). Antimicrobial activity of Nigerian medicinal plants. Journal of Intercultural Ethnopharmacology, 6(2), 240–259. https://doi.org/10.5455/jice.20170106073231 [Google Scholar] [Crossref] 
  6. Arballo, J., Amengual, J., & Erdman, Jr. J. W. (2021). Lycopene: A critical review of digestion, absorption, metabolism, and excretion. Antioxidants, 10(3), 342. https://doi.org/10.3390/antiox10030342 [Google Scholar] [Crossref] 
  7. Arzumanian, V. A., Kiseleva, O. I., & Poverennaya, E. V. (2021). The curious case of the HepG2 cell Line: 40 years of expertise. International Journal of Molecular Sciences, 22(23), 13135. https://doi.org/10.3390/ijms222313135 [Google Scholar] [Crossref] 
  8. Bin-Jumah, M. N., Nadeem, M. S., Gilani, S. J., Mubeen, B., Ullah, I., Alzarea, S. I., Ghoneim, M. M., Alshehri, S., Al-Abbasi, F. A., & Kazmi, I. (2022). Lycopene: A natural arsenal in the war against oxidative stress and cardiovascular diseases. Antioxidants, 11(2), 232. https://doi.org/10.3390/antiox11020232 [Google Scholar] [Crossref] 
  9. Cetkovic-Cvrlje, M., Rogan, S., & Barbaro, E. (2022). Garcinia kola treatment exhibits immunomodulatory properties while not affecting type 1 diabetes development in an experimental mouse model. International Journal of Immunopathology and Pharmacology, 36, 1-12. https://doi.org/10.1177/20587384211069831 [Google Scholar] [Crossref] 
  10. El-Halawany, A. M., El Dine, R. S., El Sayed, N. S., & Hattori, M. (2014). Protective effect of Aframomum melegueta phenolics against CCl4-induced rat hepatocytes damage; Role of apoptosis and pro-inflammatory cytokines inhibition. Scientific Reports, 4, 5880. https://doi.org/10.1038/srep05880 [Google Scholar] [Crossref] 
  11. Emmanuel, O., Uche, M. E., Dike, E. D., Etumnu, L. R., Ugbogu, O. C., & Ugbogu, E. A. (2022). A review on Garcinia kola Heckel: Traditional uses, phytochemistry, pharmacological activities, and toxicology. Biomarkers, 27(2), 101–117. https://doi.org/10.1080/1354750X.2021.2016974 [Google Scholar] [Crossref] 
  12. Erdman, J. W., Jr., Ford, N. A., & Lindshield, B. L. (2009). Are the health attributes of lycopene related to its antioxidant function? Archives of Biochemistry and Biophysics, 483(2), 229–235. https://doi.org/10.1016/j.abb.2008.10.022 [Google Scholar] [Crossref] 
  13. Fylaktakidou, K. C., Hadjipavlou-Litina, D. J., Litinas, K. E., & Nicolaides, D. N. (2004). Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Current Pharmaceutical Design, 10(30), 3813-3833. https://doi.org/10.2174/1381612043382710 [Google Scholar] [Crossref] 
  14. Hassan, M. F., Hussein, S. A., Senosi, Y. E., Mansour, M. K., & Amin, A. (2018). The role of lycopene as antioxidant and anti-inflammatory in protection of oxidative stress induced by metalaxyl. Journal of Medicinal Chemistry and Toxicology, 3(1), 26–36. [Google Scholar]
  15. Ibrahim, P. J., Adele, B. O., & Ige, A. O. (2024). Gastroprotective biochemicals in Wistar rats orally exposed to Bisphenol A and co-treated with either Garcinia kola (Heckel) seeds or its biflavonoid, Kolaviron. Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria, 39(1), 57-63. https://doi.org/10.54548/njps.v39i1.8 [Google Scholar] [Crossref] 
  16. Ilic, N. M., Dey, M., Poulev, A. A., Logendra, S., Kuhn, P. E., & Raskin, I. (2014). Anti-inflammatory activity of Grains of Paradise (Aframomum melegueta Schum) extract. Journal of Agricultural and Food Chemistry, 62(43), 10452–10457. https://doi.org/10.1021/jf5026086 [Google Scholar] [Crossref] 
  17. Ilic, N. M., Schmidt, B. M., Poulev, A., & Raskin, I. (2010). Toxicological evaluation of Grains of paradise (Aframomum melegueta) [Roscoe] K. Schum. Journal of Ethnopharmacology, 127(2), 352–356. https://doi.org/10.1016/j.jep.2009.10.031 [Google Scholar] [Crossref] 
  18. Kawata, A., Murakami, Y., Suzuki, S., & Fujisawa, S. (2018). Anti-inflammatory activity of β-carotene, lycopene and tri-n-butylborane, a scavenger of reactive oxygen species. In Vivo, 32(2), 255–264. https://doi.org/10.21873/invivo.11232 [Google Scholar] [Crossref] 
  19. Khan, U. M., Sevindik, M., Zarrabi, A., Nami, M., Ozdemir, B., Kaplan, D. N., Selamoglu, Z., Hasan, M., Kumar, M., Alshehri, M. M., & Sharifi-Rad, J. (2021). Lycopene: Food sources, biological activities, and human health benefits. Oxidative Medicine and Cellular Longevity, 2021(1), 2713511. https://doi.org/10.1155/2021/2713511 [Google Scholar] [Crossref] 
  20. Latif, M., Elkoraichi, I., El Faqer, O., Wahnou, H., Mtairag, E. M., Oudghiri, M., & Rais, S. (2024). Phytochemical analysis and immunomodulatory activities in vitro and in vivo of Aframomum melegueta K Schum seed extracts. Inflammopharmacology, 32(3), 1621–1631. https://doi.org/10.1007/s10787-023-01422-7 [Google Scholar] [Crossref] 
  21. Liu, C. B., Wang, R., Yi, Y. F., Gao, Z., & Chen, Y. Z. (2018). Lycopene mitigates β-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer’s disease rats. The Journal of Nutritional Biochemistry, 53, 66–71. https://doi.org/10.1016/j.jnutbio.2017.10.014 [Google Scholar] [Crossref] 
  22. Lončar, M., Jakovljević, M., Šubarić, D., Pavlić, M., Buzjak Služek, V., Cindrić, I., & Molnar, M. (2020). Coumarins in food and methods for their determination. Foods, 9(5), 645. https://doi.org/10.3390/foods9050645 [Google Scholar] [Crossref] 
  23. Mishra, S., Pandey, A., & Manvati, S. (2020). Coumarin: An emerging antiviral agent. Heliyon, 6(1), e03217. https://doi.org/10.1016/j.heliyon.2020.e03217 [Google Scholar] [Crossref] 
  24. Nworu, C. S., Akah, P. A., Esimone, C. O., Okoli, C. O., & Okoye, F. B. C. (2008). Immunomodulatory activities of kolaviron, a mixture of three related biflavonoids of Garcinia kola Heckel. Immunopharmacology and Immunotoxicology, 30(2), 317–332. https://doi.org/10.1080/08923970801949158 [Google Scholar] [Crossref] 
  25. Obioha, K. C., Ewa, O., Nweke, E. O., Ejiofor, D. C., Obasi, D. C., Ibezim, E. O., Amah, E. E., Ofoha, P. C., Ogwo, E. U., & Mbanaso, E. L. (2025). Evaluation of selected indicators of depression in mice administered ethanol seed extract of Monodora myristica (African nutmeg). Dutse Journal of Pure and Applied Sciences, 11(3d), 1-8. https://doi.org/10.4314/dujopas.v11i3d.1 [Google Scholar] [Crossref] 
  26. Okoko, T. (2009). In vitro antioxidant and free radical scavenging activities of Garcinia kola seeds. Food and Chemical Toxicology, 47(10), 2620–2623. https://doi.org/10.1016/j.fct.2009.07.023 [Google Scholar] [Crossref] 
  27. Okoli, C. O., Akah, P. A., Nwafor, S. V., Ihemelandu, U. U., & Amadife, C. (2007). Anti-inflammatory activity of seed extracts of Aframomum melegueta. Journal of Herbs, Spices & Medicinal Plants, 13(1), 11–21. https://doi.org/10.1300/J044v13n01_02 [Google Scholar] [Crossref] 
  28. Okwu, D. E., & Josiah, C. (2006). Evaluation of the chemical composition of two Nigerian medicinal plants. African Journal of Biotechnology, 5(4), 357–361. [Google Scholar]
  29. Oldenburg, J., Watzka, M., Rost, S., & Müller, C. R. (2007). VKORC1: Molecular target of coumarins. Journal of Thrombosis and Haemostasis, 5(Suppl. 1), 1–6. https://doi.org/10.1111/j.1538-7836.2007.02549.x [Google Scholar] [Crossref] 
  30. Omage, S. O., Orhue, N. E. J., & Omage, K. (2021). Dennettia tripetala combats oxidative stress, protein and lipid dyshomeostasis, inflammation, hepatic injury, and glomerular blockage in rats. Preventive Nutrition and Food Science, 26(2), 177-185. https://doi.org/10.3746/pnf.2021.26.2.177 [Google Scholar] [Crossref] 
  31. Paudel, S., Mishra, N., & Agarwal, R. (2023). Phytochemicals as immunomodulatory molecules in cancer therapeutics. Pharmaceuticals, 16(12), 1652. https://doi.org/10.3390/ph16121652 [Google Scholar] [Crossref] 
  32. Pereira, T. M., Franco, D. P., Vitorio, F., & Kummerle, A. E. (2018). Coumarin compounds in medicinal chemistry: Some important examples from the last years. Current Topics in Medicinal Chemistry, 18(2), 124–148. https://doi.org/10.2174/1568026618666180329115523 [Google Scholar] [Crossref] 
  33. Pérez-Machín, R., Vega-Morales, T., Elvira-Aranda, C., Lledó-Rico, L., Gomis-Gomis, M. J., & López-Ríos, L. (2025). Aframomum melegueta seed extract's effects on anxiety, stress, mood, and sleep: A randomized, double-blind, pilot clinical trial. Pharmaceuticals, 18(2), 278. https://doi.org/10.3390/ph18020278 [Google Scholar] [Crossref] 
  34. Przybylska, S. (2020). Lycopene – A bioactive carotenoid offering multiple health benefits: A review. International Journal of Food Science and Technology, 55(1), 11–32. https://doi.org/10.1111/ijfs.14260 [Google Scholar] [Crossref] 
  35. Ralebona, N., Sewani-Rusike, C. R., & Nkeh-Chungag, B. N. (2012). Effects of ethanolic extract of Garcinia kola on sexual behaviour and sperm parameters in male Wistar rats. African Journal of Pharmacy and Pharmacology, 6(14), 1077-1082. [Google Scholar]
  36. Rao, A. V., & Rao, L. G. (2007). Carotenoids and human health. Pharmacological Research, 55(3), 207-216. https://doi.org/10.1016/j.phrs.2007.01.012 [Google Scholar] [Crossref] 
  37. Saini, R. K., Rengasamy, K. R. R., Mahomoodally, M. F., & Keum, Y. -S. (2020). Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives. Pharmacological Research, 155, 104730. https://doi.org/10.1016/j.phrs.2020.104730 [Google Scholar] [Crossref] 
  38. Song, B., Liu, K., Gao, Y., Zhao, L., Fang, H., Li, Y., Pei, L., & Xu, Y. (2017). Lycopene and risk of cardiovascular diseases: A meta-analysis of observational studies. Molecular Nutrition & Food Research, 61(9), 1601009. https://doi.org/10.1002/mnfr.201601009 [Google Scholar] [Crossref] 
  39. Stefanachi, A., Leonetti, F., Pisani, L., Catto, M., & Carotti, A. (2018). Coumarin: A natural, privileged and versatile scaffold for bioactive compounds. Molecules, 23(2), 250. https://doi.org/10.3390/molecules23020250 [Google Scholar] [Crossref] 
  40. Tauchen, J., Frankova, A., Manourova, A., Valterova, I., Lojka, B., & Leuner, O. (2023). Garcinia kola: A critical review on chemistry and pharmacology of an important West African medicinal plant. Phytochemistry Reviews, 22, 1305-1351. https://doi.org/10.1007/s11101-023-09869-w [Google Scholar] [Crossref] 
  41. Ugbaja, R. N., James, A. S., Ugwor, E. I., Akamo, A. J., Thomas, F. C., & Kosoko, A. M. (2021). Lycopene suppresses palmitic acid-induced brain oxidative stress, hyperactivity of some neuro-signalling enzymes, and inflammation in female Wistar rat. Scientific Reports, 11, 15038. https://doi.org/10.1038/s41598-021-94518-5 [Google Scholar] [Crossref] 
  42. Ukwubile, C. A., Idriss, U., & Isah, A. M. (2022). Phytochemical evaluation, in vitro–in vivo antioxidant and cytotoxicity activities of various layers of watermelon fruit Citrullus lanatus (Cucurbitaceae) Matsum. & Nakai. Progress in Chemical and Biochemical Research, 5(1), 97-114. https://doi.org/10.22034/pcbr.2022.334538.1218 [Google Scholar] [Crossref] 
  43. Umukoro, S., & Ashorobi, B. R. (2008). Further pharmacological studies on aqueous seed extract of Aframomum melegueta in rats. Journal of Ethnopharmacology, 115(3), 489–493. https://doi.org/10.1016/j.jep.2007.10.019 [Google Scholar] [Crossref] 
  44. Vasconcelos, A. G., Amorim, A. D. G. N., Dos Santos, R. C., Souza, J. M. T., de Souza, L. K. M., Araújo, T. S. L., Nicolau, L. A. D., de Lima Carvalho, L., de Aquino, P. E. A., da Silva Martins, C., Ropke, C. D., Soares, P. M. G., Kuckelhaus, S. A. S., Medeiros, J. R., & Leite, J. R. S. A. (2017). Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice. Food Research International, 99(Pt 2), 959–968. https://doi.org/10.1016/j.foodres.2017.01.017 [Google Scholar] [Crossref] 
  45. Venugopala, K. N., Rashmi, V., & Odhav, B. (2013). Review on natural coumarin lead compounds for their pharmacological activity. BioMed Research International, 2013(1), 963248. https://doi.org/10.1155/2013/963248 [Google Scholar] [Crossref] 
  46. Wallert, M., Bauer, J., Kluge, S., Schmölz, L., Chen, Y.-C., Ziegler, M., Searle, A. K., Maxones, A., Schubert, M., Thürmer, M., Pein, H., Koeberle, A., Werz, O., Birringer, M., Peter, K., & Lorkowski, S. (2019). The vitamin E derivative garcinoic acid from Garcinia kola nut seeds attenuates the inflammatory response. Redox Biology, 24, 101166. https://doi.org/10.1016/j.redox.2019.101166 [Google Scholar] [Crossref] 
  47. Yakubu, M. T., & Quadri, A. L. (2012). Garcinia kola seeds: Is the aqueous extract a true aphrodisiac in male Wistar rats? African Journal of Traditional, Complementary and Alternative Medicines, 9(4), 530–535. https://doi.org/10.4314/ajtcam.v9i4.9 [Google Scholar] [Crossref] 
  48. Yang, P., Chen, H., Huang, Y., Hsieh, C., & Wung, B. (2017). Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells. International Journal of Molecular Medicine, 39(6), 1533–1540. https://doi.org/10.3892/ijmm.2017.2960 [Google Scholar] [Crossref] 
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