Alkaloids of Delphinium grandiflorum and their implication to H2O2-induced cardiomyocytes injury

Yali Wang; Dejuan Sun; Yanmei Chen; Jinyu Xu; Yang Xu; Xinyi Yue; Jingming Jia; Hua Li; Lixia Chen

doi:10.1016/j.bmc.2021.116113

Alkaloids of Delphinium grandiflorum and their implication to H₂O₂-induced cardiomyocytes injury

Bioorg Med Chem. 2021 May 1:37:116113. doi: 10.1016/j.bmc.2021.116113. Epub 2021 Mar 17.

Authors

Yali Wang¹, Dejuan Sun¹, Yanmei Chen¹, Jinyu Xu¹, Yang Xu¹, Xinyi Yue¹, Jingming Jia², Hua Li³, Lixia Chen⁴

Affiliations

¹ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
² Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jiajingming@163.com.
³ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: li_hua@hust.edu.cn.
⁴ Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: syzyclx@163.com.

PMID: 33744825
DOI: 10.1016/j.bmc.2021.116113

Abstract

Three new diterpenoid alkaloids (1-3), and eight known alkaloids (4-11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7NC17 hemiaminal moiety and a lactone fragment through the linkage of C-17OC19 unit. And we named this newly-discovered class of rearranged C₁₉-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C-7OC17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1-11 on H₂O₂-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC₅₀ values of 1.881 ± 0.680 μM and 1.904 ± 0.750 μM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H₂O₂-induced H9C2 cells.

Keywords: Antioxidant activity; C(19)-diterpenoid alkaloid; Delphinium grandiflorum; Grandiflodines (B-12); Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Apoptosis / drug effects
Cardiotonic Agents / chemistry
Cardiotonic Agents / isolation & purification
Cardiotonic Agents / pharmacology*
Delphinium / chemistry*
Diterpenes / chemistry
Diterpenes / isolation & purification
Diterpenes / pharmacology*
Hydrogen Peroxide / pharmacology
Myocytes, Cardiac / drug effects*
Plant Components, Aerial / chemistry
Reactive Oxygen Species / metabolism

Substances

Alkaloids
Cardiotonic Agents
Diterpenes
Reactive Oxygen Species
Hydrogen Peroxide