Phloroglucinol Derivatives Exert Anti-inflammatory Effects and Attenuate Cognitive Impairment in LPS-induced Mouse Model.

Abstract

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to haveantioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance their antioxidant and anti-inflammatory activity. Among PG derivatives, 6a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1β, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6a, is a potential treatment for neurodegenerative diseases.