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resources","award":["201900105"],"award-info":[{"award-number":["201900105"]}]},{"name":"Key project at the central government level: The ability establishment of sustainable use for valuable Chinese medicine resources","award":["2021SF-368"],"award-info":[{"award-number":["2021SF-368"]}]},{"name":"Key project at the central government level: The ability establishment of sustainable use for valuable Chinese medicine resources","award":["2060302"],"award-info":[{"award-number":["2060302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Isorhamnetin (ISO) is an active flavonoid compound mainly isolated from the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L. Previous studies have revealed the antifibrotic action of ISO in the liver and lungs, although its potential protective effects against renal fibrosis and the underlying mechanisms are still poorly understood. Given that many actions of ISO could be similarly attained by hydrogen sulfide (H2S), we speculated that ISO may work through the induction of endogenous H2S. To test the hypothesis, we established the unilateral ureteral obstruction (UUO) renal fibrosis rat model and transforming growth factor-\u03b21(TGF-\u03b21)-induced fibrosis in cultured renal tubular cells. ISO treatment inhibited epithelial\u2013mesenchymal transition (EMT) formation, decreased extracellular matrix (ECM) deposition, and relieved renal fibrosis. Further analysis revealed that ISO stimulated the expression of the H2S-synthesizing enzyme cystathionine lyase (CSE) and cystathionine beta-synthase (CBS), and promoted H2S production in vivo and in vitro. The elevated H2S attenuated oxidative stress and elevated the thiol level. It induced Keap1 sulfhydration, disrupted Keap1-Nrf2 interaction, and promoted the entry of Nrf2 into the nucleus. Finally, we found that circulating H2S mainly derived from the liver, and not the kidney. Collectively, our study revealed that ISO alleviated renal fibrosis by inducing endogenous H2S and regulating Keap1-Nrf2 interaction through sulfhydration of Keap1. Endogenous H2S could be an important mediator underlying the pharmacological actions of ISO. Due to the multifunctional properties of H2S, the H2S-inducing nature of ISO could be exploited to treat various diseases.<\/jats:p>","DOI":"10.3390\/biom14101233","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T03:12:28Z","timestamp":1727665948000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Isorhamnetin Alleviates Renal Fibrosis by Inducing Endogenous Hydrogen Sulfide and Regulating Thiol-Based Redox State in Obstructed Kidneys"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhen","family":"Zhang","sequence":"first","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanni","family":"Liang","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingao","family":"Yu","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of the Thyroid and Breast Surgery, Xianyang Central Hospital, Xianyang 712000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongxing","family":"Song","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhishu","family":"Tang","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"},{"name":"Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-0215","authenticated-orcid":false,"given":"Jian","family":"Yao","sequence":"additional","affiliation":[{"name":"Division of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tem.2023.09.001","article-title":"Mechanisms of kidney fibrosis and routes towards therapy","volume":"35","author":"Yamashita","year":"2024","journal-title":"Trends Endocrinol. 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