Planta Med
DOI: 10.1055/a-1956-7542
Original Papers

Metabolite Profiling of Talatisamine in Heart Tissue After Oral Administration and Analysis of Cardiac Bioactivities

1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
3   Yibin Institute of Southwest Jiaotong University, Yibin, Sichuan, P. R. China
,
Yang Lv
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Jian-Zhu Wang
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Mei-Zhen Ye
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Rui-Jie Lu
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Lin Chen
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Jiang Xie
2   The Affiliated Hospital of Southwest Jiaotong University, The Third Peopleʼs Hospital of Chengdu, Chengdu, Sichuan, P. R. China
,
Feng Gao
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
,
Xian-Li Zhou
1   School of Life Science and Engineering Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
2   The Affiliated Hospital of Southwest Jiaotong University, The Third Peopleʼs Hospital of Chengdu, Chengdu, Sichuan, P. R. China
› Institutsangaben
Gefördert durch: the Fundamental Research Funds for Central Universities 2682022ZTPY078
Gefördert durch: National Natural Science Foundation of China 82073734

Abstract

The lateral roots of the Aconitum carmichaelii (“Fuzi”) have been used for centuries as a cardiotonic in China. The diterpenoid alkaloid talatisamine (TA) is a major bioactive component of Fuzi, but the identity and bioactivities of the TA metabolites have not been examined in detail. In this study, metabolite profiling of TA was performed in rat heart by UPLC-MS following oral administration. Metabolites were identified by comparing protonated molecules, fragmentation patterns, and chromatographic behaviors with those of standard compounds. Metabolites of TA were then prepared and tested for cardiotonic activity on isolated frog hearts. The metabolite cammaconine, a C19 diterpenoid alkaloid with a hydroxyl group at C-18, exhibited substantial cardiotonic activity during frog heart perfusion. To further investigate the structure–cardiac effect relationships, a series of C19-diterpenoid alkaloids with 18-OH were prepared. Eight tested compounds (512) demonstrated measurable cardioactivity, of which compound 5 with an N-methyl group and compound 7 with a methoxy at C-16 showed stronger effects on ventricular contraction than the other compounds. Thus, 18-OH is a critical structural feature determining cardiotonic activity, and efficacy is improved by the presence of N-methyl or methoxy at C-16. Preliminary mechanistic studies suggested that the cardiotonic effect of compound 5 is mediated by enhanced cellular calcium influx. Metabolites of TA with these structural features may be useful therapeutics to prevent heart failure.

Supporting Information



Publikationsverlauf

Eingereicht: 28. Juni 2022

Angenommen nach Revision: 06. Oktober 2022

Accepted Manuscript online:
06. Oktober 2022

Artikel online veröffentlicht:
18. Januar 2023

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