Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.
10.1016/j.apsb.2023.01.004
- Author:
Lijuan MA
1
;
Boyi LI
2
;
Jinchen MA
2
;
Chunyuan WU
3
;
Nan LI
1
;
Kailin ZHOU
4
;
Yun YAN
2
;
Mingshuang LI
1
;
Xiaoyan HU
1
;
Hao YAN
1
;
Qi WANG
2
;
Yanfei ZHENG
2
;
Zhisheng WU
1
Author Information
1. Beijing University of Chinese Medicine, School of Chinese Materia Medica, Beijing 100029, China.
2. Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, Beijing 100029, China.
3. Shanghai New Asiatic Pharmaceuticals Hanjiang Co., Ltd., Yangzhou 225127, China.
4. Beijing University of Chinese Medicine, School of Humanities, Beijing 100029, China.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Autophagy;
Biosensor;
Male infertility;
Oligoasthenospermia;
Schisandrin A.
- From:
Acta Pharmaceutica Sinica B
2023;13(6):2765-2777
- CountryChina
- Language:English
-
Abstract:
Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.
