Medicinal Plants and Bioactive Phytochemicals Targeting Neuroinflammation: Molecular Mechanisms, Preclinical Evidence and Translational Challenges
DOI:
https://doi.org/10.67601/njbls.v3i2a.54Keywords:
Neuroinflammation, Phytochemicals, Neurodegeneration, Microglia, Neuroprotection, Oxidative stressAbstract
Neuroinflammation is the inflammatory response within the central nervous system which is linked to many neurological disoders. These disorders include Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ischemic stroke, among others. Short-term reaction to inflammation within the central nervous system has a contribution to the balance of neural homeostasis and protection of tissues but once the neuroinflammation is persistent, it may lead to the production of inflammatory mediators in excess, oxidative stress, and gradual neuronal damage. Increasing evidence suggests that persistent triggering of microglia and astrocytes, and also the disruption of signaling cascades like nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and NLRP3 inflammasome pathways, plays major role in the progression of neurodegenerative diseases. A lot of attention has been given to medicinal plants as a therapeutic agent that has prospects due to their wide range of phytochemicals and multi-target pharmacological effects. Many plant-based compounds such as curcumin, epigallocatechin-3-gallate, ginsenosides, withanolides, and bacosides have shown properties of anti-neuroinflammation and neuroprotection by inhibiting inflammatory signaling pathways, reducing microglial activation, reduction of oxidative stress, and increasing support for neuron survival. This review gives an in-depth review of medicinal plants with anti-neuroinflammatory properties, focusing on their bioactive compounds, mode of action, and clinical applications in neurological disorders. The current challenges, limitations and future research viewpoint relating to the clinical application of medicinal plant compounds are discussed. The findings show that medicinal plants are potential treatment options for neuroinflammatory disorders.
References
Aguiar, S., & Borowski, T. (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Research, 16(4), 313–326. https://doi.org/10.1089/rej.2013.1431
Ahlemeyer, B., & Krieglstein, J. (2003). Neuroprotective effects of Ginkgo biloba extract. Cellular and Molecular Life Sciences, 60(9), 1779–1792. https://doi.org/10.1007/s00018-003-3080-1
Amalraj, A., Pius, A., Gopi, S., & Gopi, S. (2017). Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives—A review. Journal of Traditional and Complementary Medicine, 7(2), 205–233. https://doi.org/10.1016/j.jtcme.2016.05.005
Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: Problems and promises. Molecular Pharmaceutics, 4(6), 807–818. https://doi.org/10.1021/mp700113r
Angelova, P. R., & Abramov, A. Y. (2018). Role of mitochondrial reactive oxygen species in the brain: From physiology to neurodegeneration. FEBS Letters, 592(5), 692–702. https://doi.org/10.1002/1873-3468.12964
Barnham, K. J., Masters, C. L., & Bush, A. I. (2004). Neurodegenerative diseases and oxidative stress. Nature Reviews Drug Discovery, 3(3), 205–214. https://doi.org/10.1038/nrd1330
Barbalho, S. M., Boaro, B. L., Oliveira, J. S. C., Patočka, J., Barbalho Lamas, C., Tanaka, M., & Laurindo, L. F. (2025). Molecular mechanisms underlying neuroinflammation intervention with medicinal plants: A critical and narrative review of the current literature. Pharmaceuticals, 18(1), 133. https://doi.org/10.3390/ph18010133
Bloem, B. R., Okun, M. S., & Klein, C. (2021). Parkinson's disease. The Lancet, 397(10291), 2284–2303. https://doi.org/10.1016/S0140-6736(21)00218-X
Campbell, B. C. V., De Silva, D. A., Macleod, M. R., Coutts, S. B., Schwamm, L. H., Davis, S. M., & Donnan, G. A. (2019). Ischaemic stroke. Nature Reviews Disease Primers, 5(1), 70. https://doi.org/10.1038/s41572-019-0118-8
Cherry, J. D., Olschowka, J. A., & O'Banion, M. K. (2014). Neuroinflammation and M2 microglia: The good, the bad, and the inflamed. Journal of Neuroinflammation, 11, 98. https://doi.org/10.1186/1742-2094-11-98
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018). 13 reasons why the brain is susceptible to oxidative stress. Redox Biology, 15, 490–503. https://doi.org/10.1016/j.redox.2018.01.008
Colonna, M., & Butovsky, O. (2017). Microglia function in the central nervous system during health and neurodegeneration. Annual Review of Immunology, 35, 441–468. https://doi.org/10.1146/annurev-immunol-051116-052358
Dai, J., & Mumper, R. J. (2010). Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules, 15(10), 7313–7352. https://doi.org/10.3390/molecules15107313
Dar, N. J., Hamid, A., & Ahmad, M. (2015). Pharmacologic overview of Withania somnifera, the Indian ginseng. Cellular and Molecular Life Sciences, 72(23), 4445–4460. https://doi.org/10.1007/s00018-015-2012-1
Ekor, M. (2014). The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4, Article 177. https://doi.org/10.3389/fphar.2013.00177
Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495–516. https://doi.org/10.1080/01926230701320337
Filippi, M., Bar-Or, A., Piehl, F., Preziosa, P., Solari, A., Vukusic, S., & Rocca, M. A. (2018). Multiple sclerosis. Nature Reviews Disease Primers, 4(1), 43. https://doi.org/10.1038/s41572-018-0041-4
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6), 918–934. https://doi.org/10.1016/j.cell.2010.02.016
Gray, N. E., Harris, C. J., Quinn, J. F., & Soumyanath, A. (2018). Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function. Scientific Reports, 8, 8881.
Habtemariam, S. (2006). The therapeutic potential of Rosmarinus officinalis diterpenes for Alzheimer's disease. Evidence-Based Complementary and Alternative Medicine, 2016, Article 2680409. https://doi.org/10.1155/2016/2680409
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., et al. (2013). NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature, 493(7434), 674–678. https://doi.org/10.1038/nature11729
Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., et al. (2015). Neuroinflammation in Alzheimer's disease. The Lancet Neurology, 14(4), 388–405. https://doi.org/10.1016/S1474-4422(15)70016-5
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015). Immune attack: The role of inflammation in Alzheimer disease. Nature Reviews Neuroscience, 16(6), 358–372. https://doi.org/10.1038/nrn3880
Hewlings, S. J., & Kalman, D. S. (2017). Curcumin: A review of its effects on human health. Foods, 6(10), 92. https://doi.org/10.3390/foods6100092
Iadecola, C., Buckwalter, M. S., & Anrather, J. (2020). Immune responses to stroke: Mechanisms, modulation, and therapeutic potential. The Journal of Clinical Investigation, 130(6), 2777–2788. https://doi.org/10.1172/JCI135530
Kaur, N., Chugh, H., Sakharkar, M. K., Dhawan, U., Chidambaram, S. B., & Chandra, R. (2020). Neuroinflammation mechanisms and phytotherapeutic intervention: A systematic review. ACS Chemical Neuroscience, 11(22), 3707–3731. https://doi.org/10.1021/acschemneuro.0c00427
Khan, H., Ullah, H., Aschner, M., Cheang, W. S., Akkol, E. K., & Nabavi, S. M. (2021). Neuroprotective effects of phytochemicals and their therapeutic potential against neurodegenerative diseases. Food and Chemical Toxicology, 148, 111979.
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
Kim, J. H., Yi, Y. S., Kim, M. Y., & Cho, J. Y. (2018). Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. Journal of Ginseng Research, 41(4), 435–443. https://doi.org/10.1016/j.jgr.2016.08.004
Kongkeaw, C., Dilokthornsakul, P., Thanarangsarit, P., Limpeanchob, N., & Scholfield, C. N. (2014). Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. Journal of Ethnopharmacology, 151(1), 528–535. https://doi.org/10.1016/j.jep.2013.11.008
Kuboyama, T., Tohda, C., & Komatsu, K. (2006). Neuritic regeneration and synaptic reconstruction induced by withanolide A. British Journal of Pharmacology, 144(7), 961–971. https://doi.org/10.1038/sj.bjp.0706122
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
Leng, F., & Edison, P. (2021). Neuroinflammation and microglial activation in Alzheimer's disease: Where do we go from here? Nature Reviews Neurology, 17(3), 157–172. https://doi.org/10.1038/s41582-020-00435-y
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541(7638), 481–487. https://doi.org/10.1038/nature21029
Liu, B., Hong, J. S., & Wilson, B. (2018). Neuroinflammation: Mechanisms and therapeutic targets in neurodegenerative diseases. Acta Pharmacologica Sinica, 39(5), 699–710.
Liu, H., Lu, J., & Kwon, O. (2020). Panax ginseng and its active constituents for neuroprotection: A review. Journal of Ginseng Research, 44(4), 549–559. https://doi.org/10.1016/j.jgr.2019.09.004
Loane, D. J., & Kumar, A. (2016). Microglia in the TBI brain: The good, the bad, and the dysregulated. Experimental Neurology, 275(Pt. 3), 316–327. https://doi.org/10.1016/j.expneurol.2015.08.018
Mak, I. W., Evaniew, N., & Ghert, M. (2014). Lost in translation: Animal models and clinical trials in cancer treatment. American Journal of Translational Research, 6(2), 114–118.
Mandel, S., Amit, T., Reznichenko, L., Weinreb, O., & Youdim, M. B. H. (2008). Green tea catechins as brain-permeable, non-toxic iron chelators. Journal of Neural Transmission Supplementum, 73, 249–257. https://doi.org/10.1007/978-3-211-33328-0_26
Mandel, S., Weinreb, O., Amit, T., & Youdim, M. B. H. (2011). Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: Implications for neurodegenerative diseases. Journal of Neurochemistry, 88(6), 1555–1569. https://doi.org/10.1046/j.1471-4159.2003.02291.x
Mashhadi, N. S., Ghiasvand, R., Askari, G., Hariri, M., Darvishi, L., & Mofid, M. R. (2013). Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: Review of current evidence. International Journal of Preventive Medicine, 4(Suppl. 1), S36–S42.
Mattson, M. P. (2007). Calorie restriction and disease prevention: A mechanism involving neuroprotective and anti-aging pathways. Ageing Research Reviews, 6(2), 97–110.
Miller, A. H., & Raison, C. L. (2016). The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nature Reviews Immunology, 16(1), 22–34. https://doi.org/10.1038/nri.2015.5
Owemidu, I. O., Ajayi, A.M., & Onasanwo, S.A. (2022). Anti-neuroinflammatory properties of Waltheria americana L.leaf in experimental animals. Phytomedicine Plus, 2(1), 100217. https://doi.org/10.1016/j.phyplu.2022.100217
Pardridge, W. M. (2012). Drug transport across the blood–brain barrier. Journal of Cerebral Blood Flow & Metabolism, 32(11), 1959–1972. https://doi.org/10.1038/jcbfm.2012.126
Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A. E., & Lang, A. E. (2017). Parkinson disease. Nature Reviews Disease Primers, 3, 17013. https://doi.org/10.1038/nrdp.2017.13
Posadzki, P., Watson, L., & Ernst, E. (2013). Herb–drug interactions: An overview of systematic reviews. British Journal of Clinical Pharmacology, 75(3), 603–618. https://doi.org/10.1111/j.1365-2125.2012.04350.x
Postorino, M. C., Kurnik, M., Harkin, K., & McAuliffe, J. J. (2018). Inflammation in autism spectrum disorders: A systematic review. Neural Plasticity, 2018, Article 1923124.
Ransohoff, R. M. (2016). How neuroinflammation contributes to neurodegeneration. Science, 353(6301), 777–783. https://doi.org/10.1126/science.aag2590
Ratan, Z. A., Haidere, M. F., Hong, Y. H., Park, S. H., Lee, J.-O., Lee, J., & Cho, J. Y. (2021). Pharmacological potential of ginseng and its major component ginsenosides. Journal of Ginseng Research, 45(2), 199–210. https://doi.org/10.1016/j.jgr.2020.02.004
Reich, D. S., Lucchinetti, C. F., & Calabresi, P. A. (2018). Multiple sclerosis. New England Journal of Medicine, 378(2), 169–180. https://doi.org/10.1056/NEJMra1401483
Semwal, R. B., Semwal, D. K., Combrinck, S., & Viljoen, A. M. (2015). Gingerols and shogaols: Important nutraceutical principles from ginger. Phytochemistry, 117, 554–568. https://doi.org/10.1016/j.phytochem.2015.07.012
Shen, Y., Zhang, H., Liu, X., Wang, J., Li, Q., & Chen, L. (2024). Medicinal plants and phytochemicals in the management of neuroinflammation and neurodegenerative diseases: Molecular mechanisms and therapeutic prospects. Pharmacological Research, 203, 107197. https://doi.org/10.1016/j.phrs.2024.107197
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017). The far-reaching scope of neuroinflammation after traumatic brain injury. Nature Reviews Neurology, 13(3), 171–191. https://doi.org/10.1038/nrneurol.2017.13
Swanson, K. V., Deng, M., & Ting, J. P. Y. (2019). The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nature Reviews Immunology, 19(8), 477–489. https://doi.org/10.1038/s41577-019-0165-0
Voet, S., Prinz, M., & van Loo, G. (2019). Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends in Molecular Medicine, 25(2), 112–123. https://doi.org/10.1016/j.molmed.2018.11.005
Wang, J., Li, Y., Zhang, X., Liu, H., & Chen, Z. (2021). Oxidative stress and neuroinflammation in neurodegenerative diseases: Molecular mechanisms and therapeutic strategies. Frontiers in Aging Neuroscience, 13, 740587. https://doi.org/10.3389/fnagi.2021.740587
Wang, X., Zhao, Y., Liu, Y., Zhang, H., & Li, J. (2023). Mitochondrial dysfunction and neuronal apoptosis in neurodegenerative diseases: Emerging therapeutic targets. Cell Death & Disease, 14, 487.
Weinreb, O., Mandel, S., Amit, T., & Youdim, M. B. H. (2004). Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. Journal of Nutritional Biochemistry, 15(9), 506–516. https://doi.org/10.1016/j.jnutbio.2004.05.002
Yao, L., Kan, E. M., Lu, J., Hao, A., Dheen, S. T., & Kaur, C. (2020). Toll-like receptor 4 mediates microglial activation and neuroinflammation in neurological disorders. Brain, Behavior, and Immunity, 88, 635–647. https://doi.org/10.1016/j.bbi.2020.04.067
Zhao, L., Sun, Y., Wang, H., Chen, X., Zhang, Y., & Liu, C. (2025). Plant-derived bioactive compounds targeting neuroinflammation: Recent advances and future perspectives. Journal of Neuroinflammation, 22(1), 41
