Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2׳-hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases.
Keywords: 2׳-Hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone; Anti-neuroinflammatory activities; Ap-1; Inflammatory mediators; Signaling pathways.
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