Differential Immunomodulatory and Antioxidative Mechanisms of Lycopene and Coumarin Derivatives in Nigerian Medicinal Plants: A Comprehensive Meta-Analysis With Therapeutic Implications
DOI:
https://doi.org/10.61326/actanatsci.v7i1.390Keywords:
Lycopene, Coumarin, Immunomodulation, Nigerian Medicinal Plants, Antioxidant mechanisms, Nigerian medicinal plantsAbstract
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.
References
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
Okwu, D. E., & Josiah, C. (2006). Evaluation of the chemical composition of two Nigerian medicinal plants. African Journal of Biotechnology, 5(4), 357–361.
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
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
Paudel, S., Mishra, N., & Agarwal, R. (2023). Phytochemicals as immunomodulatory molecules in cancer therapeutics. Pharmaceuticals, 16(12), 1652. https://doi.org/10.3390/ph16121652
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Mathew Folaranmi Olaniyan, Odekunle Bola Odegbemi, Moyinoluwa Elizabeth Babatunde , Godfrey Innocent Iyare

This work is licensed under a Creative Commons Attribution 4.0 International License.
