The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice

Abstract

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE 2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Methyl p‑hydroxycinnamate exerts anti‑inflammatory effects in mouse models of lipopolysaccharide‑induced ARDS

“…LPS-induced ROS generation leads to excessive inflammation and oxidative damage ( 35 , 36 ) and the induction of the antioxidant protein HO-1 exerts protective effects against LPS-induced pulmonary inflammation and oxidative stress in mice ( 6 , 19 , 37 , 38 ). Inhibition of expression of cytokines (TNF-α, IL-6 and IL-1β), chemokines (MCP-1) and inflammatory mediators (iNOS) and of activation of p38MAPK/NF-κB is accompanied by HO-1 upregulation.…”

“…To detect HO-1 expression, cells were seeded into 6-well plates (5x10 Inflammatory cell count and ELISA. To evaluate the number of inflammatory cells and levels of inflammatory molecules in bronchoalveolar lavage fluid (BALF), BALF was collected as previously described (19). The mice were anesthetized with Zoletil 50 (30-50 mg/kg i.p.…”

“…; Virbac) and xylazine (5-10 mg/kg i.p. ; Bayer-Korea, ltd.) on day 3, as previously described (19).…”

“…; Virbac) and xylazine (5–10 mg/kg i.p. ; Bayer-Korea, Ltd.) on day 3, as previously described ( 19 ). Tracheal PBS perfusion was performed 24 h after the final intraperitoneal treatment of MH and DEX, and BALF was collected from all groups.…”

“…no. c3228; SigmaAldrich; Merck KGaA) in the presence of protease and phosphatase inhibitor cocktail as previously described ( 19 ) and protein quantification was performed using BCA assay. Then, the protein (50 µg/lane) was separated with 10–12% SDS-PAGE and transferred to PVDF membranes.…”