Abstract
The crisis of male infertility is an issue of human reproductive health worldwide. The Wuzi Yanzong pill (WZYZP) is a traditional Chinese medicine prescription that shows efficacy in kidney reinforcement and essence benefit to ameliorate male reproductive dysfunctions. However, the pharmacological mechanisms of the WZYZP on male infertility have not been investigated and clarified clearly. This study was designed to investigate the effects of the WZYZP on spermatogenesis disorder and explore its underlying pharmacological mechanisms. First, based on a network pharmacology study, 39 bioactive compounds and 40 targets of the WZYZP associated with spermatogenesis disorder were obtained, forming a tight compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified TP53, TNF, AKT1, Bcl-XL, Bcl-2, and IκBA as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Subsequently, the chemical characterization of WZYZP was analyzed using liquid chromatography to quadrupole/time-of-flight mass spectrometry, and 40 compounds in positive ion mode and 41 compounds in negative ion mode in the WZYZP were identified. Furthermore, based on the prediction of a network pharmacology study, a rat model of spermatogenesis disorder was established to evaluate the curative role and underlying mechanisms of the WZYZP. The results showed that WZYZP treatment improved rat sperm quality and attenuated serum hormone levels, reversed histopathological damage of the testis, reduced cell apoptosis in testis tissues, and ameliorated the expression of the predicted hub targets (TP53, TNF-α, AKT1, NFκB, and IκBA) and the apoptosis related proteins (Bcl-XL, Bcl-2, Bax, Caspase 3, and Caspase 9). These results indicated that the WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.
Highlights
Male infertility is in crisis as a human reproductive health-related issue, accounting for approximately 40% of the infertility cases worldwide (Jonge and Barratt, 2019)
Based on the TCM systems pharmacology database and analysis platform (TCMSP) database and the criterion of ADME parameters (OB, drug likeness (DL), Caco-2), a total of 72 bioactive compounds were retrieved from Wuzi Yanzong pill (WZYZP)
The spermatogenesis is a complex process, with three phases: first, the primitive germ cells or spermatogonia undergo a series of mitotic divisions into spermatocytes; second, the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids; and third, the spermatids are differentiated into functional sperms (Chocu et al, 2012)
Summary
Male infertility is in crisis as a human reproductive health-related issue, accounting for approximately 40% of the infertility cases worldwide (Jonge and Barratt, 2019). Evidence from global reports have described declining sperm counts and a persisting upward trend in male reproductive system abnormalities (Kilchevsky and Honig, 2012; Barratt et al, 2017). Factors such as genetics, endocrinopathies, lifestyle, and adverse environmental exposure seem to be responsible for the risks of male infertility (Brugh et al, 2003; Skakkebaek et al, 2016). Surgical and medical management are still the main strategies for male infertility treatment (Schiff et al, 2007). Compared to surgical therapy, which is mainly focused on overcoming anatomical defects and pathophysiology abnormalities, medical therapy is available to cure hormonal abnormalities, improve sperm quality, and remedy sexual dysfunction (Brannigan, 2019)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
