Discovery of natural compounds and their derivatives against neuroinflammation: Pharmacological mechanisms and structure-activity relationship

Neuroinflammation refers to the inflammatory response within the central nervous system mediated by immune and glial cells, constitutes a pivotal mechanism in the pathological progression of neurodegenerative diseases. Alzheimer's disease (AD) serves as a paradigmatic example of neuroinflammation role in driving cytokine-mediated neuronal damage and perpetuating of disease progression. AD, which is characterized by memory decline and progressive cognitive impairment as its core clinical manifestations, currently has no effective treatment. Recent advances have underscored natural products as promising candidates for the development of safer and more effective anti-AD agents, particularly through the targeting of neuroinflammatory pathways that have emerged as central pathological mechanisms in the progression of AD. This review aims to elucidate the pathogenesis of neuroinflammation in AD and provides a comprehensive overview of anti-AD drugs currently in clinical research as well as those already available on the market. Additionally, this paper highlights natural compounds and their derivatives discovered over the past decade that exhibit anti-AD neuroinflammatory properties, analyzing the structure-activity relationships of selected compounds and their permeability across the blood-brain barrier. The goal is to offer valuable insights and references for drug developers.

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