Studies on the mechanism of anti-inflammatory action of swietenine, a tetranortriterpenoid isolated from Swietenia macrophylla seeds
Kit‐Kay Mak, Shiming Zhang, Madhu Katyayani Balijepalli, Albena T. Dinkova‐Kostova, Ola Epemolu, Mohd Zulkefeli, Mallikarjuna Rao Pichika
Abstract
Swietenia macrophylla seeds possess diverse biological activities in which inflammation is the primary cause, and swietenine is the main tetranortriterpenoid present. The purpose of the study is to investigate the molecular mechanisms involved in the anti-inflammatory activity of swietenine and its cytoprotective effect. The anti-inflammatory activity of swietenine and its molecular mechanisms were evaluated using LPSEc- stimulated RAW 264.7 cells. The cytoprotective effect of swietenine was evaluated via determining NRF2 inducing activity in Hepa-1c1c7 cells. The in vitro metabolic stability of swietenine was assessed using mouse, rat and human liver microsomes. Swietenine showed dose-dependent effect in inhibiting NO production, downregulating pro-inflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-6) and mediators (NF-κB and COX-2); and increasing the levels of NRF2, and HO-1 in LPSEc-stimulated RAW264.7 cells. Swietenine also induced NQO1 activity, a classical marker of NRF2 activation, in Hepa-1c1c7 cells. In addition, swietenine was metabolically stable in mouse, rat, and human liver microsomes. The results suggest that the anti-inflammatory effect of swietenine is mediated by the down-regulation of pro-inflammatory cytokines and mediators and the activation of cytoprotective NRF2/HO-1 pathway.