Xiaocui Jiang , Xiaoming Yu , Zhongyi Zhu , Yinjuan Lyu , Xingyu Jiang , Zihao Liu , Jigang Cao , Min Xiao
{"title":"参苓白珠散通过调节Sirt3/Nrf2抑制睾丸铁下垂改善高尿酸血症小鼠生精功能障碍。","authors":"Xiaocui Jiang , Xiaoming Yu , Zhongyi Zhu , Yinjuan Lyu , Xingyu Jiang , Zihao Liu , Jigang Cao , Min Xiao","doi":"10.1016/j.jep.2024.119310","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The effect of hyperuricemia (HUA) on testicular spermatogenesis cannot be ignored. The classical Chinese medicine compound Shenling Baizhu San (SLBZS) can reduce uric acid and improve testicular spermatogenesis, while researchers have not well explored the related pathology and pharmacodynamic mechanism have.</div></div><div><h3>Aims of study</h3><div>To investigate whether the dysfunction of testicular spermatogenesis caused by HUA and the therapeutic effect of SLBZS are related to testicular cell ferroptosis.</div></div><div><h3>Materials and methods</h3><div>C57BL/6 mice and C57BL/6 background Sirt3<sup>−/−</sup> mice were induced by oxazinate potassium (OXO), and HUA spermatogenic dysfunction mice model were constructed and treated with SLBZS. Sperm quality detection and testicular histopathology served for evaluating the protective mechanism of SLBZS against testicular spermatogenesis in HUA mice. Biochemical detection, transmission electron microscopy, immunohistochemistry and immunofluorescence were used to evaluate ferroptosis level of testicular cells. Western blot analysis assisted in verifying the expression of the corresponding pathway proteins.</div></div><div><h3>Results</h3><div>The testes of mice with HUA spermatogenic dysfunction were subjected to OXO-induced oxidative stress and ferroptosis, and the Sirt3/Nrf2 pathway-related protein expressions were changed. SLBZS improved the testes of mice with HUA spermatogenic dysfunction in terms of their spermatogenic function, oxidative stress and ferroptosis, and promoted Sirt3/Nrf2 antioxidant pathway-related proteins to be expressed. The analysis of Sirt3<sup>−/−</sup> mice was modeled and dosed, and it was found that SLBZS could not improve the spermatogenic function, oxidative stress and ferroptosis of Sirt3-deficient model mice’ testes.</div></div><div><h3>Conclusions</h3><div>OXO-induced spermatogenic dysfunction in HUA is associated with ferroptosis of testicular cells. SLBZS can be used for treating spermatogenic dysfunction in HUA possibly by activating Sirt3/Nrf2 signaling pathway, which inhibits ferroptosis due to oxidative stress.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119310"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Shenling Baizhu San improves spermatogenic dysfunction in hyperuricemia mice by regulating Sirt3/Nrf2 to inhibit testicular ferroptosis\",\"authors\":\"Xiaocui Jiang , Xiaoming Yu , Zhongyi Zhu , Yinjuan Lyu , Xingyu Jiang , Zihao Liu , Jigang Cao , Min Xiao\",\"doi\":\"10.1016/j.jep.2024.119310\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><div>The effect of hyperuricemia (HUA) on testicular spermatogenesis cannot be ignored. The classical Chinese medicine compound Shenling Baizhu San (SLBZS) can reduce uric acid and improve testicular spermatogenesis, while researchers have not well explored the related pathology and pharmacodynamic mechanism have.</div></div><div><h3>Aims of study</h3><div>To investigate whether the dysfunction of testicular spermatogenesis caused by HUA and the therapeutic effect of SLBZS are related to testicular cell ferroptosis.</div></div><div><h3>Materials and methods</h3><div>C57BL/6 mice and C57BL/6 background Sirt3<sup>−/−</sup> mice were induced by oxazinate potassium (OXO), and HUA spermatogenic dysfunction mice model were constructed and treated with SLBZS. Sperm quality detection and testicular histopathology served for evaluating the protective mechanism of SLBZS against testicular spermatogenesis in HUA mice. Biochemical detection, transmission electron microscopy, immunohistochemistry and immunofluorescence were used to evaluate ferroptosis level of testicular cells. Western blot analysis assisted in verifying the expression of the corresponding pathway proteins.</div></div><div><h3>Results</h3><div>The testes of mice with HUA spermatogenic dysfunction were subjected to OXO-induced oxidative stress and ferroptosis, and the Sirt3/Nrf2 pathway-related protein expressions were changed. SLBZS improved the testes of mice with HUA spermatogenic dysfunction in terms of their spermatogenic function, oxidative stress and ferroptosis, and promoted Sirt3/Nrf2 antioxidant pathway-related proteins to be expressed. The analysis of Sirt3<sup>−/−</sup> mice was modeled and dosed, and it was found that SLBZS could not improve the spermatogenic function, oxidative stress and ferroptosis of Sirt3-deficient model mice’ testes.</div></div><div><h3>Conclusions</h3><div>OXO-induced spermatogenic dysfunction in HUA is associated with ferroptosis of testicular cells. SLBZS can be used for treating spermatogenic dysfunction in HUA possibly by activating Sirt3/Nrf2 signaling pathway, which inhibits ferroptosis due to oxidative stress.</div></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"340 \",\"pages\":\"Article 119310\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S037887412401609X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S037887412401609X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Shenling Baizhu San improves spermatogenic dysfunction in hyperuricemia mice by regulating Sirt3/Nrf2 to inhibit testicular ferroptosis
Ethnopharmacological relevance
The effect of hyperuricemia (HUA) on testicular spermatogenesis cannot be ignored. The classical Chinese medicine compound Shenling Baizhu San (SLBZS) can reduce uric acid and improve testicular spermatogenesis, while researchers have not well explored the related pathology and pharmacodynamic mechanism have.
Aims of study
To investigate whether the dysfunction of testicular spermatogenesis caused by HUA and the therapeutic effect of SLBZS are related to testicular cell ferroptosis.
Materials and methods
C57BL/6 mice and C57BL/6 background Sirt3−/− mice were induced by oxazinate potassium (OXO), and HUA spermatogenic dysfunction mice model were constructed and treated with SLBZS. Sperm quality detection and testicular histopathology served for evaluating the protective mechanism of SLBZS against testicular spermatogenesis in HUA mice. Biochemical detection, transmission electron microscopy, immunohistochemistry and immunofluorescence were used to evaluate ferroptosis level of testicular cells. Western blot analysis assisted in verifying the expression of the corresponding pathway proteins.
Results
The testes of mice with HUA spermatogenic dysfunction were subjected to OXO-induced oxidative stress and ferroptosis, and the Sirt3/Nrf2 pathway-related protein expressions were changed. SLBZS improved the testes of mice with HUA spermatogenic dysfunction in terms of their spermatogenic function, oxidative stress and ferroptosis, and promoted Sirt3/Nrf2 antioxidant pathway-related proteins to be expressed. The analysis of Sirt3−/− mice was modeled and dosed, and it was found that SLBZS could not improve the spermatogenic function, oxidative stress and ferroptosis of Sirt3-deficient model mice’ testes.
Conclusions
OXO-induced spermatogenic dysfunction in HUA is associated with ferroptosis of testicular cells. SLBZS can be used for treating spermatogenic dysfunction in HUA possibly by activating Sirt3/Nrf2 signaling pathway, which inhibits ferroptosis due to oxidative stress.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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