Neuroinflammatory Link between Arthritis and Central Nervous System Dysfunction, and the Therapeutic Potential of Plant-derived Bioactives: ASystematic Review

Introduction: Arthritis is not merely a localized joint disorder, but a systemic inflammatory disease, with the joint-brain axis, which is characterized by peripheral chronic inflammation, compromising the blood-brain barrier that further leads to comorbidities in the central nervous system. This work examines the role of systemic inflammatory spillover and intestinal dysbiosis in the development of neuroinflammation and evaluates the therapeutic potential of plant-derived bioactives, such as Curcumin, Quercetin, and boswellic acids, in regulating this inflammatory continuum. Methods: A literature search was performed in PubMed, Scopus, and Web of Science, with the MeSH terms and keywords, including: arthritis, neuroinflammation, and plant-derived bioactives, focusing on those that were published within the past 10-15 years with quantitative data, such as the HPLC/LC-MS characterization and the IC50 values. Inclusion involved mechanistic research on the joint-brain axis, BBB dysfunction, glial stimulation, CNS comorbidity, and two-sided action bioactives. Further, the information was organized into key areas, including peripheral signaling and molecular pharmacology. Results: Pro-inflammatory cytokines (TNF-α, IL-6) and gut endotoxins facilitate microglial activation, cognitive impairment, and BBB permeability through the tight junction down-regulation and MMPs. Multi-target anti-inflammatory efficacy of phytochemicals is only achievable with poor bioavailability; lipophilicity, BBB entry, and dual peripheral-central delivery are promoted by phytosomes and nanocarriers. Discussion: Plant bioactives such as curcumin (NF-kB/MAPK inhibitor, IC50 5-20 mM) and quercetin (NLRP3/TNF-α suppressor, IC50 1.5-10 mM) provide dual joint and neuroprotection. Advanced delivery systems further enhance their bioavailability, offering potential therapeutic benefits against neuro-arthritic comorbidities, including pain sensitization. However, challenges such as poor standardization and the need for longitudinal human studies continue to limit their clinical translation. Conclusion: The bioactives of plants with phytosomes/nanocarriers act as a mediator between peripheral and CNS pathophysiology in arthritis by restoring a systemic-neurological balance; large-scale clinical research is necessary in the future to demonstrate the disease-modifying capabilities.