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

Abstract

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.

Keywords: Janus kinase/signal transducer and activator of transcription (JAK/STAT); NLRP3 inflammasome; medicinal plants; microglia; neurodegenerative diseases; neuroinflammation; nuclear factor erythroid 2-related factor 2 (Nrf2); nuclear factor kappa B (NF-κB); oxidative stress; phytochemicals.

Figure 1

Microglia have M1 and M2 phenotypes depending on conditions. In a homeostatic state, they support neuronal health through synaptic pruning and clearing misfolded proteins. Under stress, they shift to the pro-inflammatory M1 phenotype, releasing Reactive Oxygen Species (ROS) and cytokines that can damage neurons. When exposed to Transforming Growth Factor Beta (TGF-β), interleukin (IL)-4, IL-10, or IL-13, they switch to the anti-inflammatory M2 phenotype, aiding in phagocytosis, Extracellular Matrix (ECM) rebuilding, and neuronal survival. Abbreviations: ARG, Arginase; BDNF, Brain-Derived Neurotrophic Factor; CCL, Chemokine (C-C motif) Ligand; CD, Cluster of Differentiation; CSF, Colony-Stimulating Factor; FGF, Fibroblast Growth Factor; GNDF, Glial cell line Derived Neurotrophic Factor; IGF, Insulin-like Growth Factor; IFN-γ, Interferon Gamma; iNOS, Inducible Nitric Oxide Synthase; LPS, Lipopolysaccharide; MHC-II, Major Histocompatibility Complex Class II; STAT, Signal Transducer and Activator of Transcription; TNF-α, Tumor Necrosis Factor-Alpha.

Figure 2

Key actions of medicinal plants in countering neuroinflammation and related disorders. Abbreviations: CREB, Cyclic AMP Response Element-Binding Protein; HO-1, Heme Oxygenase-1; Nrf2, Nuclear Factor Erythroid 2-Related Factor 2.