2. Academic Validation
  3. A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes

A class of geranylquinol-derived polycyclic meroterpenoids from Arnebia euchroma against heart failure by reducing excessive autophagy and apoptosis in cardiomyocytes

  • Bioorg Chem. 2024 Oct:151:107691. doi: 10.1016/j.bioorg.2024.107691.
Ling-Hao Zhao 1,  Xin-Yi Guo 2,  Hai-Wei Yan 1,  Jian-Shuang Jiang 1,  Xu Zhang 1,  Ya-Nan Yang 1,  Xiang Yuan 3,  Hua Sun 4,  Pei-Cheng Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2 State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinses Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: yuanxiang@imm.ac.cn.
  • 4 State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinses Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: sunhua@imm.ac.cn.
  • 5 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: pczhang@imm.ac.cn.
PMID: 39116524 DOI: 10.1016/j.bioorg.2024.107691
Abstract

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive Autophagy, and decreasing myocardial Apoptosis.

Keywords

Arnebia euchroma; Autophagy and apoptosis; Heart failure; Isoprenaline (ISO); Methyl 1,2-shift; Polycyclic meroterpenoids.

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