Three new monoterpenes compounds isolated from Seriphidium terrae-albae exerted anti-inflammatory effects through the JAK/STAT and NF-κB signaling pathways.

Abstract

Three new monoterpenes compounds (5S, 8S)-5-(2E-butenyl)-8-methyl propionate-cyclopentanone (1), 1-Oxy, 10-keto-α-myrcene hydroxide (2), (3R,4R)-3-hydroxy-4-isobutenyl-cyclopentyl ester (3), along with eleven known small molecular compounds such as monoterpenes (1-7, 14), coumarin (10), and other small molecular compounds (8, 9, 11-13) were isolated from Seriphidium terrae-albae. The structures were elucidated by NMR, HRESIMS, ECD calculations, and X-ray crystallography. Anti-inflammatory activity test results showed that 9 compounds were detected to inhibit NO secretion by mouse macrophage Raw 264.7. Among them, the IC₅₀ value of compound 1 (9.56 ± 0.66 μM) was relatively close to the positive control drug Andrographolide (AG) (2.70 ± 0.39 μM). Molecular docking predicted that the target of compound 1 may be the STAT3 proteins. Further mechanism studies have revealed that compound 1 acted on the STAT3 target in the JAK/STAT signaling pathway, indicating the activation of M2 macrophages, exerted anti-inflammatory effects. Additionally, it could also reduce the cytoplasmic NF-κB content achieve the anti-inflammatory effect. Therefore, compound 1 has the potential to become an anti-inflammatory lead compound. This study provides reference value for the research and development of small-molecule natural product anti-inflammatory drugs.