Chukrasia tabularis limonoid plays anti-inflammatory role by regulating NF-κB signaling pathway in lipopolysaccharide-induced macrophages.

ABSTRACT

Background: Chukrasia tabularisis, a well-known tropical tree native to southeastern China, has anti-inflammatory and antioxidant activities, and contains large amounts of limonoids and triterpenoids. Objective: The aim of this study was to investigate the potential anti-inflammatory activity of limonoids from C. tabularis on lipopolysaccharide (LPS)-mediated RAW264.7 cells. Methods and results: Using a bioassay-guided approach, the chemical fraction with high anti-inflammatory activity was found and its chemical constituents were investigated. Phytochemical studies on active extracts resulted in the separation of three novel phragmalin limonoids (1-3), together with two known limonoids (4-5) and 11 tirucallane triterpenes (6-16). The activity of these isolated compounds in the production of nitric oxide (NO) on LPS-reated macrophages was evaluated. Limonoid 2 indicated significant anti-inflammatory activities with IC50 value of 4.58 µM. Limonoid 2 notably inhibited the production of NO, interleukin- 6 and tumor necrosis factor-α on macrophage. Signal transduction and activation of STAT and NF-κB activators were effectively blocked by limonoid 2. Conclusions: These results indicate that limonoid 2 has an anti-inflammatory effect by the inhibiting JAK2/STAT3, iNOS/eNOS, and NF-κB signaling pathways and regulating inflammatory mediators.