Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.

Danube Neuroscience Research Laboratory HUN REN SZTE Neuroscience Research Group Hungarian Research Network University of Szeged Tisza Lajos Krt 113 H 6725 Szeged Hungary

Department of Biochemistry and Pharmacology School of Medicine Faculdade de Medicina de Marília Marília 17519 030 São Paulo Brazil

Department of Biochemistry and Pharmacology School of Medicine Universidade de Marília Marília 17525 902 São Paulo Brazil

Department of Chemistry Faculty of Science University of Hradec Kralove 50003 Hradec Kralove Czech Republic

Department of Gerontology School of Gerontology Universidade Federal de São Carlos São Carlos 13565 905 São Paulo Brazil

Faculty of Health and Social Studies Institute of Radiology Toxicology and Civil Protection University of South Bohemia Ceske Budejovice 37005 Ceske Budejovice Czech Republic

Postgraduate Program in Structural and Functional Interactions in Rehabilitation School of Medicine Universidade de Marília Marília 17525 902 São Paulo Brazil

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