Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways

Abstract

Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of Psoralea corylifolia L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells’ inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells’ (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses.

Keywords

• inflammation
• NF-κB
• chalcone
• macrophages
• isodorsmanin A
• RAW 264.7