Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis
Context Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge), is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investig...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2025.2498166 |
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| author | Xueling Yang Qinglin Luo Zhifen Wu Chunxuan Wang Yuanjing Yang Luquan Zheng Ke Li Lei Zhao Yang Jurong |
| author_facet | Xueling Yang Qinglin Luo Zhifen Wu Chunxuan Wang Yuanjing Yang Luquan Zheng Ke Li Lei Zhao Yang Jurong |
| author_sort | Xueling Yang |
| collection | DOAJ |
| description | Context Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge), is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.Objective This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.Materials and methods Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.Results Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. In vitro studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.Discussion and conclusions Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction. |
| format | Article |
| id | doaj-art-97aeed937a3c4464a4e1aaa655418319 |
| institution | DOAJ |
| issn | 1388-0209 1744-5116 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj-art-97aeed937a3c4464a4e1aaa6554183192025-08-20T02:57:17ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162025-12-0163136437310.1080/13880209.2025.2498166Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosisXueling Yang0Qinglin Luo1Zhifen Wu2Chunxuan Wang3Yuanjing Yang4Luquan Zheng5Ke Li6Lei Zhao7Yang Jurong8Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaCore Research Laboratory, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaContext Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge), is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.Objective This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.Materials and methods Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.Results Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. In vitro studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.Discussion and conclusions Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.https://www.tandfonline.com/doi/10.1080/13880209.2025.2498166Chinese herbal medicineunilateral ureteral obstructioncell deathchronic kidney diseaseGasdermin Dpyroptosis |
| spellingShingle | Xueling Yang Qinglin Luo Zhifen Wu Chunxuan Wang Yuanjing Yang Luquan Zheng Ke Li Lei Zhao Yang Jurong Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis Pharmaceutical Biology Chinese herbal medicine unilateral ureteral obstruction cell death chronic kidney disease Gasdermin D pyroptosis |
| title | Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis |
| title_full | Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis |
| title_fullStr | Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis |
| title_full_unstemmed | Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis |
| title_short | Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis |
| title_sort | tanshinone iia reduces tubulointerstitial fibrosis by suppressing gsdmd mediated pyroptosis |
| topic | Chinese herbal medicine unilateral ureteral obstruction cell death chronic kidney disease Gasdermin D pyroptosis |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2025.2498166 |
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