Chemical constituents of Ajuga forrestii and their anti-ferroptosis activity

Huiwen Shi; Xiufen Jiang; Liudan Cao; Xing Peng; Qingyun Tan; Xifeng Teng; Qiong Gu; Lin He

doi:10.1016/j.fitote.2023.105461

Chemical constituents of Ajuga forrestii and their anti-ferroptosis activity

Fitoterapia. 2023 Apr:166:105461. doi: 10.1016/j.fitote.2023.105461. Epub 2023 Feb 18.

Authors

Huiwen Shi¹, Xiufen Jiang¹, Liudan Cao¹, Xing Peng², Qingyun Tan², Xifeng Teng³, Qiong Gu⁴, Lin He⁵

Affiliations

¹ Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
² Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
³ Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Key Laboratory of Lingnan Medicinal Materials Production and Development, National Administration of Traditional Chinese Medicine, Guangzhou 510006, PR China.
⁴ Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: guqiong@mail.sysu.edu.cn.
⁵ Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Provincial Engineering and Technology Research Center of Cosmetics, Guangdong Pharmaceutical University, Zhongshan 528458, PR China. Electronic address: helin@gdpu.edu.cn.

PMID: 36804655
DOI: 10.1016/j.fitote.2023.105461

Abstract

Six new neoclerodane diterpenoids (1-6), along with ten known compounds (7-16), were isolated from Ajuga forrestii. Their structures were elucidated by HRESIMS, 1D and 2D NMR, ECD calculation, and single-crystal X-ray diffraction analysis. The structure of a known neoclerodane diterpene ajudecunoid C (6) was revised based on the reported NMR empirical rules. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis in HT22 mouse hippocampal neuronal cells. Among them, compounds 8, 9, and 12 significantly inhibited RSL3-induced ferroptosis with EC₅₀ values of 0.45 μM, 0.076 μM, and 0.14 μM.

Keywords: Ajuga. Forrestii; Anti-ferroptosis activity; Neoclerodane diterpene.

MeSH terms

Ajuga* / chemistry
Animals
Cell Line, Tumor
Crystallography, X-Ray
Magnetic Resonance Spectroscopy
Mice
Molecular Structure