Benzophenone and Benzoylphloroglucinol Derivatives from with Anti-Inflammatory Mechanism of Otogirinin A.

Three new compounds, 4-geranyloxy-2-hydroxy-6-isoprenyloxybenzophenone (), hypericumone A () and hypericumone B (), were obtained from the aerial parts of , along with six known compounds (-). The structures of these compounds were determined through spectroscopic and MS analyses. Hypericumone A (), sampsonione J () and otogirinin A () exhibited potent inhibition (IC values ≤ 40.32 μM) against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. Otogirinin A () possessed the highest inhibitory effect on production with IC value of 32.87 ± 1.60 μM. The well-known proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also inhibited by otogirinin A (). Western blot results demonstrated that otogirinin A () downregulated the high expression of inducible nitric oxide synthase (iNOS). Further investigations on the mechanism showed that otogirinin A () blocked the phosphorylation of MAPK/JNK and IκBα, whereas it showed no effect on the phosphorylation of MAPKs/ERK and p38. In addition, otogirinin A () stimulated anti-inflammatory M2 phenotype by elevating the expression of arginase 1 and Krüppel-like factor 4 (KLF4). The above results suggested that otogirinin A () could be considered as potential compound for further development of NO production-targeted anti-inflammatory agent.