{"title":"Mechanism of salidroside promoting testosterone secretion induced by H<sub>2</sub>O<sub>2</sub> in TM3 Leydig cells based on metabolomics and network pharmacology.","authors":"Zixu Wang, Yunlong Xu, Huazhong Xiong","doi":"10.3389/fchem.2025.1544876","DOIUrl":null,"url":null,"abstract":"<p><p>Oxidative stress-induced damage is a significant contributor to the impairment of Leydig cells in the testes, potentially diminishing the secretion of testosterone and other androgens, thereby resulting in testosterone deficiency. Salidroside, the principal bioactive constituent derived from Rhodiola, exhibits potent antioxidant properties. This study aims to investigate the underlying mechanisms by which salidroside enhances testosterone secretion. The study investigated the oxidative damage in TM3 cells induced by H<sub>2</sub>O<sub>2</sub> and demonstrated that salidroside significantly decreased the levels of ROS and MDA, while increasing the levels of testosterone, SOD, GSH. These changes effectively ameliorated oxidative stress, mitigated oxidative damage, protected TM3 cells, and enhanced testosterone secretion. Additionally, UPLC-QE-Orbitrap-MS was employed to analyze the metabolomics of TM3 cells, identifying 28 distinct metabolites and associated metabolic pathways. Key metabolic pathways identified include Arginine biosynthesis, Alanine, aspartate and glutamate metabolism, Citrate cycle (TCA cycle), Phenylalanine metabolism, Pyruvate metabolism. Utilizing network pharmacology, the core targets of salidroside in enhancing testosterone secretion were further investigated, revealing the involvement of AMACR, CYP3A4, ECHS1, HSD17B10, MPO, and TYR. This discovery was confirmed by dry-wet analysis. To sum up, salidroside can reduce the level of oxidative stress and promote testosterone secretion through multiple metabolic pathways and multiple targets. In a word, salidroside may provide a new strategy for preventing and treating testosterone deficiency.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"13 ","pages":"1544876"},"PeriodicalIF":4.2000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904911/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.3389/fchem.2025.1544876","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Oxidative stress-induced damage is a significant contributor to the impairment of Leydig cells in the testes, potentially diminishing the secretion of testosterone and other androgens, thereby resulting in testosterone deficiency. Salidroside, the principal bioactive constituent derived from Rhodiola, exhibits potent antioxidant properties. This study aims to investigate the underlying mechanisms by which salidroside enhances testosterone secretion. The study investigated the oxidative damage in TM3 cells induced by H2O2 and demonstrated that salidroside significantly decreased the levels of ROS and MDA, while increasing the levels of testosterone, SOD, GSH. These changes effectively ameliorated oxidative stress, mitigated oxidative damage, protected TM3 cells, and enhanced testosterone secretion. Additionally, UPLC-QE-Orbitrap-MS was employed to analyze the metabolomics of TM3 cells, identifying 28 distinct metabolites and associated metabolic pathways. Key metabolic pathways identified include Arginine biosynthesis, Alanine, aspartate and glutamate metabolism, Citrate cycle (TCA cycle), Phenylalanine metabolism, Pyruvate metabolism. Utilizing network pharmacology, the core targets of salidroside in enhancing testosterone secretion were further investigated, revealing the involvement of AMACR, CYP3A4, ECHS1, HSD17B10, MPO, and TYR. This discovery was confirmed by dry-wet analysis. To sum up, salidroside can reduce the level of oxidative stress and promote testosterone secretion through multiple metabolic pathways and multiple targets. In a word, salidroside may provide a new strategy for preventing and treating testosterone deficiency.
期刊介绍：
Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide.
Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”.
All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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