期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 41, 期 8, 页码 1219-1227出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b18-00037
关键词
O-methylbulbocapnine; dicentrine; lipopolysaccharide; inflammation
资金
- Faculty of Medicine Research Fund [074/2559]
- Faculty of Medicine, Chiang Mai University, Thailand
- Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand
The natural aporphine alkaloids including crebanine (CN), O-methylbulbocapnine (OMP), and dicentrine (DC), and protoberberine alkaloids, tetrahydropalmatine (THP) and N-methyl tetrahydropalmatine (NTHP), have been found in Stephania venosa. Previous reports demonstrated CN and THP exhibited anti-inflammatory properties. In this study, we investigated anti-inflammatory effect of CN analogs including OMP, DC, THP, and NTHP in RAW264.7 macrophages. The pre-treatment of macrophages with CN, OMP and DC suppressed lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators including interleukin-6 (IL-6), tumor necrosis factor alpha, prostaglandin E2 and nitric oxide, in which the rank-order of inhibitory potency was DC>CN >= OMP. Whereas, high dose THP (30-40 mu g/mL) reduced LPS-induced IL-6 production in RAW264.7 cells but NTHP did not effect. Moreover, CN, OMP and DC inhibited the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. OMP and DC inhibited LPS-induced nuclear factor kappa B (NF-kappa B) activation by suppressing the phosphorylation of NF-kappa B at Ser536, but not the nucleus translocation and inhibitor of kappaB (I kappa B)-alpha degradation. In addition, OMP and DC also reduced the phosphorylation and nucleus translocation of activator protein-1 (AP-1). Furthermore, OMP and DC suppressed the LPS-activated myeloid differentiation factor 88 (MyD88), Akt and mitogen-activated protein kinases (MAPKs) signaling pathway, which were the upstream signaling regulators of AP-1 and NF-kappa B. Collectively, OMP and DC have an anti-inflammatory effect on RAW264.7 macrophages by the suppression of pro-inflammatory cytokines and mediators. The inhibitory property of OMP and DC is mediated by blockage the activation of MyD88, MAPKs, Akt, NF-kappa B and AP-1 signaling molecules.
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