Anti-inflammatory polyoxygenated cyclohexene derivatives from Uvaria macclurei

Abstract

Two undescribed polyoxygenated seco-cyclohexene derivatives named macclureins A and B, and three undescribed polyoxygenated cyclohexene derivatives macclureins C–E, together with 15 known analogues were isolated from the twigs and leaves of Uvaria macclurei. Their structures were established by extensive spectroscopic and circular dichroism analyses. Macclurein C is a chlorinated polyoxygenated cyclohexene. All isolates were evaluated for their anti-inflammatory activities on NO generation in the LPS-stimulated RAW 264.7 cells. (−)-Zeylenone showed the most potent effect against NO production with the IC50 value of 20.18 μM. Meanwhile, (−)-zeylenone also decreased the mRNA expression of pro-inflammatory factors IFN-γ, iNOS, IL-6 and TNF-α via downregulating NF-κB signaling pathway. Further in vivo experiments using a mouse model of sepsis showed that (−)-zeylenone significantly alleviated sepsis severity by measuring weight, murine sepsis score, survival rate and the serum levels of pro-inflammatory factors TNF-α and IL-6.