Anti-inflammatory polyoxygenated cyclohexene derivatives from Uvaria macclurei

Yexin Cheng; Hailong Li; Dan Wu; Yayue Hu; Jinhe Li; Ying Yang; Jiahang Li; Honggang Zhou; Hongfeng Zhang; Chunfeng Xie; Cheng Yang

doi:10.1016/j.phytochem.2023.113797

Anti-inflammatory polyoxygenated cyclohexene derivatives from Uvaria macclurei

Phytochemistry. 2023 Oct:214:113797. doi: 10.1016/j.phytochem.2023.113797. Epub 2023 Jul 24.

Authors

Yexin Cheng¹, Hailong Li¹, Dan Wu¹, Yayue Hu², Jinhe Li², Ying Yang², Jiahang Li², Honggang Zhou¹, Hongfeng Zhang³, Chunfeng Xie⁴, Cheng Yang⁵

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China.
² State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China; High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin 300070, People's Republic of China.
³ Department of Rheumatology and Immunology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116001, People's Republic of China. Electronic address: zhanghongfeng09@sina.com.
⁴ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China. Electronic address: xiechunfeng@nankai.edu.cn.
⁵ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, People's Republic of China. Electronic address: cheng.yang@nankai.edu.cn.

PMID: 37495182
DOI: 10.1016/j.phytochem.2023.113797

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.

Keywords: Annonaceae; Anti-inflammatory activities; NF-κB signaling pathway; Polyoxygenated cyclohexene derivatives; Sepsis; Uvaria macclurei.