Competitive CatSper Activators of Progesterone from Rhynchosia volubilis

Jin Xiang; Hang Kang; Hong-Gang Li; Yu-Long Shi; Ya-Li Zhang; Chang-Lei Ruan; Lin-Hui Liu; Han-Qi Gao; Tao Luo; Gao-Sheng Hu; Wei-Liang Zhu; Jing-Ming Jia; Jia-Chun Chen; Jin-Bo Fang

doi:10.1055/a-1542-0151

Planta Medica, Inhaltsverzeichnis

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‡

¹School 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‡

²Institute 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‡

³Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

,

Yu-Long Shi

⁵CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

⁶School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

,

Ya-Li Zhang

⁴School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China

,

Chang-Lei Ruan

¹School 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

¹School 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

¹School 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

²Institute 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

⁴School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China

,

Wei-Liang Zhu

⁵CAS Key Laboratory of Receptor Research & Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

⁶School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

,

Jing-Ming Jia

⁴School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China

,

Jia-Chun Chen

¹School 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

¹School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

› Institutsangaben

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

Volltext

Referenzen

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Zusatzmaterial

Supporting Information