Sesquiterpene lactones from Artemisia verlotorum and their anti-inflammatory activities

Mengyu Wang; Yue Yang; Changqiang Ke; Sheng Yao; Zheling Feng; Chunping Tang; Yang Ye

doi:10.1016/j.fitote.2023.105560

Sesquiterpene lactones from Artemisia verlotorum and their anti-inflammatory activities

Fitoterapia. 2023 Sep:169:105560. doi: 10.1016/j.fitote.2023.105560. Epub 2023 Jun 9.

Authors

Mengyu Wang¹, Yue Yang², Changqiang Ke², Sheng Yao³, Zheling Feng², Chunping Tang², Yang Ye⁴

Affiliations

¹ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
⁴ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: yye@simm.ac.cn.

PMID: 37302761
DOI: 10.1016/j.fitote.2023.105560

Abstract

Seven new sesquiterpenoids (1-7) and 19 known analogues were isolated from the whole plant of Artemisia verlotorum. Their structures were determined by extensive analysis of 1D and 2D NMR and HRESIMS data, electronic circular dichroism (ECD) spectra, density functional theory (DFT) NMR calculations, and time dependent density functional theory (TDDFT) ECD calculations. The absolute configurations of 1, 3, 5 and 7 were confirmed by single crystal X-ray diffraction experiments. Compounds 1 and 2 possess a rarely reported 5/8-bicyclic skeleton, while both compounds 3 and 4 were uncommon iphionane-type sesquiterpenoids. Eudesmane sesquiterpenoids (5-17) reported in this study are all 7,8-cis-lactones, of which, compound 7 represents the first eudesmane sesquiterpene with an oxygen bridge connecting C-5 and C-11. All the compounds were tested in vitro for their anti-inflammatory activities in LPS-stimulated RAW 264.7 murine macrophages. Compound 18 showed a potent inhibitory effect on NO production, with IC₅₀ values of 3.08 ± 0.61 μM.

Keywords: Anti-inflammation; Artemisia verlotorum; DFT NMR calculation; TDDFT ECD calculation; Verlotolides A–G; X-ray diffraction.

MeSH terms

Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology
Artemisia* / chemistry
Lactones / chemistry
Lactones / pharmacology
Mice
Molecular Structure
Phytochemicals / pharmacology
Sesquiterpenes* / chemistry
Sesquiterpenes* / pharmacology

Substances

Anti-Inflammatory Agents
Sesquiterpenes
Phytochemicals
Lactones