Mining of antioxidant sesquiterpene lactones from the aerial parts of Saussurea involucrata with feature-based molecular network strategy

Bodou Zhang; Lianting Liang; Jingwen Zhao; Sheng Li; Yong Sun; Lijun Fu; Xiumin Zhang; Wenyi Kang; Yu Zhang

doi:10.1016/j.bioorg.2024.108067

Mining of antioxidant sesquiterpene lactones from the aerial parts of Saussurea involucrata with feature-based molecular network strategy

Bioorg Chem. 2024 Dec 16:154:108067. doi: 10.1016/j.bioorg.2024.108067. Online ahead of print.

Authors

Bodou Zhang¹, Lianting Liang², Jingwen Zhao³, Sheng Li³, Yong Sun⁴, Lijun Fu⁴, Xiumin Zhang⁴, Wenyi Kang⁵, Yu Zhang⁶

Affiliations

¹ Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China.
³ Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
⁴ Beijing Academy of Food Sciences, Beijing 10068, China.
⁵ National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China. Electronic address: kangweny@hotmail.com.
⁶ Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: zhangyu@mail.kib.ac.cn.

PMID: 39705936
DOI: 10.1016/j.bioorg.2024.108067

Abstract

Sesquiterpene lactones (SLs) are a class of natural products with diverse structural scaffoldings and biological activities, making them intriguing objects in the fields of pharmaceutical industry, drug development, and pharmacology. Herein, fifteen SLs, including eleven undescribed SLs compounds sauruintones A-K (1-8 and 13-15), were isolated and identified from the aerial parts of Saussurea involucrata. Their structures were characterized by using mass spectrometry, spectroscopic methods, computational calculations, and single crystal X-ray diffraction. The Feature-Based Molecular Network (FBMN) strategy was utilized for the annotation of SLs with their MS/MS fragmentation patterns. Most of the SLs exerted their protective effects against oxidative stress by enhancing the levels of antioxidant enzyme (CAT) and reducing the malondialdehyde (MDA) levels. Among them, compound 12 exhibited potent reactive oxygen species (ROS) inhibitory activities and enhanced the activities of CAT, superoxide dismutase (SOD), and glutathione peroxidase (GSH), and decreased the content of MDA at concentrations of 10-25 μM. Further RT-qPCR assays and western blot analysis revealed it reduced the level of ROS by activating the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway.

Keywords: Antioxidant activity; Feature-Based Molecular Network (FBMN); Nrf-2 signaling pathway; Saussurea involucrata; Sesquiterpene lactones.