Octacosanol Attenuates Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis

Abstract

Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.

δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

“…Consistent with the nuclear translocation data, luciferase reporter assays found that δ-tocotrienol significantly inhibited NF-κB and AP-1 activities in a dose-dependent manner, as shown in Figure 7 A,B. MAPKs are found to be close with AP-1 and NF-κB activations [ 29 , 32 ]. Our results suggest that δ-tocotrienol may affect inflammatory cytokine expressions via MAPK/NF-κB and MAPK/AP-1 pathways.…”

“…Total RNA from murine macrophages RAW 264.7 cells was extracted by the Trizol reagent kit (Transgen, Beijing, China) and was then reverse transcribed by using high-Capacity cDNA Reverse Transcription Kits (Applied Biosystems, Foster City, CA, USA). Consistent with Liu et al [ 28 ] and Guo et al [ 32 ], the relative mRNA expression levels of pro-inflammatory factors and iNOS were analyzed by real-time quantitative PCR (RT-qPCR). Cells were treated with δ-tocotrienol (5 μM, 10 μM, 20 μM) for 2 h followed by adding LPS (1 µg/mL) for 6 h. According to the manufacturer’s protocol, 1 μg total RNA extracted from RAW264.7 cells was used in reverse transcription reaction with the One Step RT-PCR kit (Gibco-BRL).…”

“…RAW264.7 cells were cultured in RPMI 1640 medium that was supplemented with 10% FBS (Gibco-BRL, Carlsbad, CA, USA) at 37 °C in a humidified incubator with 5% CO 2 atmosphere. The experiment details were described in our recent publication [ 32 ]. δ-Tocotrienol that was extracted from rice bran was dissolved in ethanol.…”

“…PCR amplifications were carried out for 32 cycles and each cycle consisted of a denaturing step for 3 min at 94 °C, a further denaturing at 94 °C for 30 s, an annealing step for 30 s at 60 °C and a polymerization step for 1 min at 72 °C. The PCR primer was according to Guo’s publication [ 32 ].…”

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

“…TrkB-PLC/IP3 pathway is mainly consisted of protein-tyrosine kinase receptor B (TrkB), phospholipase C (PLC) and inositol triphosphate (IP3). After the specific binding of brain-derived neurotrophic factor (BDNF) to TrkB, TrkB is phosphorylated to p-TrkB, which activates the signal transduction of PLC/IP3 in the downstream, thereby playing roles in the increase of intracellular Ca 2+ concentration, the enhancement of nerve-muscle excitation conduction, the promotion of cell mobility in the intestinal smooth muscle, and the promotion of intestinal motility [14][15][16][17][18][19]. At present, there is no research showing the regulatory mechanism of TrkB-PLC/IP3 pathway on colitis.…”