Diterpenoids and C13 Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis

Yue-Qian Li; Bo-Lin Hou; Mei-Jie Wang; Ru-Yue Wang; Xiao-Han Chen; Xu Liu; Dong-Qing Fei; Zhan-Xin Zhang; Er-Wei Li

doi:10.3389/fchem.2022.861278

Diterpenoids and C₁₃ Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis

Front Chem. 2022 Mar 28:10:861278. doi: 10.3389/fchem.2022.861278. eCollection 2022.

Authors

Yue-Qian Li^{1

2

3}, Bo-Lin Hou^{2

4}, Mei-Jie Wang¹, Ru-Yue Wang¹, Xiao-Han Chen¹, Xu Liu¹, Dong-Qing Fei^{1

5}, Zhan-Xin Zhang¹, Er-Wei Li^{2

3}

Affiliations

¹ School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, China.
² State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
³ Institutional Center for Shared Technologies and Facilities, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, China.

Abstract

Croton yanhuii (Family Euphorbiaceae) is an annual aromatic plant endemic to Yunnan Province, China, which yields an aromatic, spicy oil used as a flavoring and fragrance. The aim of the present study was to acquire secondary metabolites from the leaves and twigs of C. yanhuii and to evaluate their cytotoxic activity. Five new diterpenoids, croyanhuins A-E (1-5), and one new C₁₃ nor-isoprenoid, croyanhuin F (6), were isolated from the leaves and twigs of C. yanhuii. Their structures and absolute configurations were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS) and confirmed by electronic circular dichroism (ECD) spectra or single-crystal X-ray diffraction analysis. Among the new terpenoids, compounds 1 and 3 inhibited cell proliferation and viability in a dose- and time-dependent manner, whereas both induced cleavage of either caspase-3 or PARP-1 in the SW480 cell line. Additionally, we observed that Z-YVAD-FMK and Z-VAD-FMK, two caspase inhibitors, inhibited the compound-dependent cell viability loss, suggesting that either of them can induce pyroptosis and caspase-dependent apoptosis. These biological assay results revealed that compounds 1 and 3 induce different kinds of programmed cell death in SW480 cells.

Keywords: C13 nor-isoprenoid; Croton yanhuii; Euphorbiaceae; cell apoptosis; diterpenoid; pyroptosis.