Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway
Abstract Zhilong Huoxue Tongyu capsule (ZL) is wildly used as a Chinese patent medicine for the treatment of cardiovascular diseases. Clinical studies have found that it can significantly improve hypertension and heart failure. However, its precise molecular mechanisms remain incompletely understood...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-10631-9 |
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| author | Qiuyu Liu Dingshan Zhang Raoqiong Wang Shihan Sun Yuanyuan Li Zhenxun Wan Yumei Qian Xinrui Yang Gang Luo Mingtai Chen Mengnan Liu |
| author_facet | Qiuyu Liu Dingshan Zhang Raoqiong Wang Shihan Sun Yuanyuan Li Zhenxun Wan Yumei Qian Xinrui Yang Gang Luo Mingtai Chen Mengnan Liu |
| author_sort | Qiuyu Liu |
| collection | DOAJ |
| description | Abstract Zhilong Huoxue Tongyu capsule (ZL) is wildly used as a Chinese patent medicine for the treatment of cardiovascular diseases. Clinical studies have found that it can significantly improve hypertension and heart failure. However, its precise molecular mechanisms remain incompletely understood. The aim of this study was to investigate the effect of ZL on myocardial fibrosis (MF) in in vivo and its potential mechanisms. We established a hypertensive MF model by subcutaneous pumping of angiotensin II (Ang II) into mice, and validated in vivo whether ZL can reduce systolic blood pressure (SBP) and inhibit MF, including the use of echocardiography and various pathological staining techniques. Mechanistically, Western blot, qRT-PCR, and various immunostaining techniques were used to verify whether ZL can regulate TGF-β1/Smad3/Erbb4-IR/miR-29b pathway, and in vivo overexpression of Erbb4-IR was used to clarify whether it plays a key role in this pathway. ZL significantly reduced SBP in hypertensive MF mice, improved cardiac function and MF. Deposition of various collagen, expression of inflammatory factors, and activation of TGF-β1/Smad3 pathway is inhibited due to the intervention of ZL. In addition, ZL significantly reduced expression of Erbb4-IR and increased the expression of miR-29b. Mechanistically, after overexpression of Erbb4-IR in vivo, the regulatory effect of ZL on TGF-β1/Smad3/Erbb4-IR/miR-29b was reversed. Our results initially demonstrated ZL could exert cardioprotective effects in hypertensive MF mice. The pharmacological mechanism of ZL may be related to its regulation on TGF-β1/Smad3/Erbb4-IR/miR-29b pathway. |
| format | Article |
| id | doaj-art-a6485a441cd54734bf6d0d5a1b5ce5ea |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a6485a441cd54734bf6d0d5a1b5ce5ea2025-08-20T04:01:49ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-10631-9Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathwayQiuyu Liu0Dingshan Zhang1Raoqiong Wang2Shihan Sun3Yuanyuan Li4Zhenxun Wan5Yumei Qian6Xinrui Yang7Gang Luo8Mingtai Chen9Mengnan Liu10School of Pharmacy, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityA Chinese Medicine Guangdong Laboratory (Hengqin Laboratory)Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Cardiovascular Disease, Shenzhen Traditional Chinese Medicine HospitalAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAbstract Zhilong Huoxue Tongyu capsule (ZL) is wildly used as a Chinese patent medicine for the treatment of cardiovascular diseases. Clinical studies have found that it can significantly improve hypertension and heart failure. However, its precise molecular mechanisms remain incompletely understood. The aim of this study was to investigate the effect of ZL on myocardial fibrosis (MF) in in vivo and its potential mechanisms. We established a hypertensive MF model by subcutaneous pumping of angiotensin II (Ang II) into mice, and validated in vivo whether ZL can reduce systolic blood pressure (SBP) and inhibit MF, including the use of echocardiography and various pathological staining techniques. Mechanistically, Western blot, qRT-PCR, and various immunostaining techniques were used to verify whether ZL can regulate TGF-β1/Smad3/Erbb4-IR/miR-29b pathway, and in vivo overexpression of Erbb4-IR was used to clarify whether it plays a key role in this pathway. ZL significantly reduced SBP in hypertensive MF mice, improved cardiac function and MF. Deposition of various collagen, expression of inflammatory factors, and activation of TGF-β1/Smad3 pathway is inhibited due to the intervention of ZL. In addition, ZL significantly reduced expression of Erbb4-IR and increased the expression of miR-29b. Mechanistically, after overexpression of Erbb4-IR in vivo, the regulatory effect of ZL on TGF-β1/Smad3/Erbb4-IR/miR-29b was reversed. Our results initially demonstrated ZL could exert cardioprotective effects in hypertensive MF mice. The pharmacological mechanism of ZL may be related to its regulation on TGF-β1/Smad3/Erbb4-IR/miR-29b pathway.https://doi.org/10.1038/s41598-025-10631-9Zhilong Huoxue Tongyu capsuleHypertensiveHeart failureMyocardial fibrosisTGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| spellingShingle | Qiuyu Liu Dingshan Zhang Raoqiong Wang Shihan Sun Yuanyuan Li Zhenxun Wan Yumei Qian Xinrui Yang Gang Luo Mingtai Chen Mengnan Liu Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway Scientific Reports Zhilong Huoxue Tongyu capsule Hypertensive Heart failure Myocardial fibrosis TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title | Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title_full | Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title_fullStr | Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title_full_unstemmed | Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title_short | Zhilong Huoxue Tongyu capsule inhibits hypertensive myocardial fibrosis via balancing TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| title_sort | zhilong huoxue tongyu capsule inhibits hypertensive myocardial fibrosis via balancing tgf β1 smad3 erbb4 ir mir 29b pathway |
| topic | Zhilong Huoxue Tongyu capsule Hypertensive Heart failure Myocardial fibrosis TGF-β1/Smad3/Erbb4-IR/miR-29b pathway |
| url | https://doi.org/10.1038/s41598-025-10631-9 |
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