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

Molecules

Tzu-Cheng Chang¹  Yun Chen²  Jih-Jung Chen²  Chun-Yi Huang²  Yu-Jing Wu³ 

[1] Department of Forestry and Natural Resources, National Ilan University, Yilan City 26047, Taiwan;Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan;Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan;

关键词: Hypericum sampsonii;    Hypericaceae;    structure elucidation;    benzophenone;    benzoylphloroglucinol derivative;    anti-inflammatory activity;   

DOI  :  10.3390/molecules25194463

来源: DOAJ

【 摘 要 】

Three new compounds, 4-geranyloxy-2-hydroxy-6-isoprenyloxybenzophenone (1), hypericumone A (2) and hypericumone B (3), were obtained from the aerial parts of Hypericum sampsonii, along with six known compounds (4–9). The structures of these compounds were determined through spectroscopic and MS analyses. Hypericumone A (2), sampsonione J (8) and otogirinin A (9) exhibited potent inhibition (IC₅₀ values ≤ 40.32 μM) against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. Otogirinin A (9) possessed the highest inhibitory effect on NO production with IC₅₀ value of 32.87 ± 1.60 μM. The well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α) was also inhibited by otogirinin A (9). Western blot results demonstrated that otogirinin A (9) downregulated the high expression of inducible nitric oxide synthase (iNOS). Further investigations on the mechanism showed that otogirinin A (9) 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 (9) 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 (9) could be considered as potential compound for further development of NO production-targeted anti-inflammatory agent.

【 授权许可】

Unknown