Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by 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 exacer-bated 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 condi-tions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical im-plications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. Key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNFα, IL-6, IL-1β), inhibit enzymes (COX-2, 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, 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 applica-bility in neurodegenerative disease management.