Kobophenol A (KPA) is a biologically active natural compound isolated from the roots of Caragana sinica (Buc'hoz) Rehder (C. sinica). However, the anti-inflammatory effects of KPA have not been reported. This study aims to find out whether KPA isolated from roots of C. sinica can act as a potential substance on inflammation and analyze the molecular mechanism using the lipopolysaccharide (LPS)-stimulated J774 A.1 macrophage cell line. We showed that KPA treatment significantly suppressed the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner without cytotoxicity. In the KPA also inhibited pro-inflammatory cytokine gene expression and production, such as interleukin-1β (IL-1β) and interleukin-6 (IL-6) in LPS-stimulated J774 A.1 cells. As continuing study on the mechanisms involved, we confirmed that these effects of KPA were related to the inhibition of nuclear factor-κB (NF-κB) pathway including the suppression of IκB kinase α/β (IKKα/β) phosphorylation and translocation of NF-κB into the nucleus. Taken together, the present study is the first to demonstrate that KPA isolated from C. sinica suppresses the expression of inflammatory mediators and cytokines by inhibiting NF-κB nuclear translocation in LPS-stimulated J774 A.1 macrophages. KPA may be a potential candidate for the treatment of inflammatory diseases in the future.
Keywords: C. sinica, Caragana sinica; IKKα/β, IκB kinase α/β; IL-1β, interleukin-1β; IL-6, interleukin-6; IκB, inhibitory κB; KPA, Kobophenol A; LPS, lipopolysaccharide; MAPKs, Mitogen-activated protein kinases; NF-κB, nuclear factor-κB; NO, nitric oxide; NSAIDs, nonsteroidal anti-inflammatory drugs; PGE2, Prostaglandin E2; TNF-α, tumor necrosis factor-α; iNOS, inducible nitric oxide synthase; inducible nitric oxide synthase; kobophenol A; nitric oxide; nuclear factor-κB; pro-inflammatory cytokines.