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CC BY-NC-ND 4.0 · Planta Med 2022; 88(11): 881-890
DOI: 10.1055/a-1542-0151
Biological and Pharmacological Activity
Original Papers

Competitive CatSper Activators of Progesterone from Rhynchosia volubilis

Jin Xiang‡
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Hang Kang‡
2   Institute of Life Science and School of Life Science, Nanchang University, Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, China
,
Hong-Gang Li‡
3   Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Yu-Long Shi
5   CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
6   School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
,
Ya-Li Zhang
4   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
,
Chang-Lei Ruan
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Lin-Hui Liu
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Han-Qi Gao
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Tao Luo
2   Institute of Life Science and School of Life Science, Nanchang University, Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, China
,
Gao-Sheng Hu
4   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
,
Wei-Liang Zhu
5   CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
6   School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
,
Jing-Ming Jia
4   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
,
Jia-Chun Chen
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Jin-Bo Fang
1   School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
› Author AffiliationsSupported by: the Fundamental Research Funds for the Central Universities HUST2016YXMS145
Supported by: the Special funds for central government to guide local scientific and Technological Development 20202ZDB01013
Supported by: the National Natural Science Foundation of China No.31000150
Supported by: the Open Funds of State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics of China T152602
Supported by: the National Key Research and Development Plan of China 2016YFC1000905
› Further Information
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Abstract

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A – E (1 – 5), a new natural product, 5′-O-methylphaseolinisoflavan (6) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7 – 18). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

Key words

Leguminosae - Rhynchosia volubilis - CatSper - prenylated isoflavonoids - rhynchones A – E

Supporting Information

    HR-ESI-MS, NMR spectra, and ECD of compounds 1 – 5, and effect of extracts and compounds 1 – 18 on human sperm [Ca2+]i are available as Supporting Information.

  • Supporting Information


Publication History

Received: 22 February 2021

Accepted after revision: 21 June 2021

Article published online:
06 August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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