Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors  

作　　者：Lijuan Ma Boyi Li Jinchen Ma Chunyuan Wu Nan Li Kailin Zhou Yun Yan Mingshuang Li Xiaoyan Hu Hao Yan Qi Wang Yanfei Zheng Zhisheng Wu 

机构地区：[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 [5]Engineering Research Center of Ministry of Education for Traditional Chinese Medicine Pharmaceutical and New Drug Development,Beijing 100029,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第6期2765-2777,共13页药学学报（英文版）

基　　金：co-supported by National Outstanding Youth Science Fund Project of National Natural Science Foundation of China(No.82022073);National Natural Science Foundation of China(No.82174389);Natural Science Foundation of Beijing Municipality(No.7202115,China);Postdoctoral Research Foundation of China(No.2021M690474)。

摘　　要：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(K_(D))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 K_(D) 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.

关 键 词：OLIGOASTHENOSPERMIA Male infertility AUTOPHAGY APOPTOSIS BIOSENSOR Schisandrin A. 

分 类 号：R285[医药卫生—中药学]