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 IC ₅₀ 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.