Benzannulated 5,5-spiroketal sesquiterpenes from the roots of Angelica Pubescens

Abstract

Two new tetrahydrobenzannulated 5,5-spiroketal sesquiterpenes (1 and 2) and three novel benzannulated 5,5-spiroketal sesquiterpenes (3–5) namely angepubesins A-E, together with a new heliannane-type benzannulated sesquiterpene namely angepubesin F (6) and two known monoterpenes (7 and 8), were isolated from the roots of Angelica Pubescens. Their structures were identified by various spectroscopic analyses (NMR, MS, UV, IR), in combination with 13C NMR calculation as well as MAE, CMAE, DP4 + and MAEΔΔδ values analyses. The absolute configurations of 1–6 were determined by modified Mosher′s method, ECD calculation and single-crystal X-ray diffraction (Cu Kα). Furthermore, the inhibitory activities of these isolated compounds against nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells were evaluated. The results showed that compounds 2–4, 6 and 7, especially 6, displayed markedly inhibitory effects on NO production in a concentration-dependent manner. Mechanical study revealed that compound 6 could significantly inhibit the expression of nitric oxide synthase (iNOS) protein at a concentration of 10 μM. In addition, compound 6 suppressed the activation of JAK-STAT and NF-κB pathways.