2. Academic Validation
  3. Qianyang Yuyin granules alleviate hypertension-induced vascular remodeling by inhibiting the phenotypic switch of vascular smooth muscle cells

Qianyang Yuyin granules alleviate hypertension-induced vascular remodeling by inhibiting the phenotypic switch of vascular smooth muscle cells

  • J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118896. doi: 10.1016/j.jep.2024.118896.
Yadong Fan 1,  Dinala Jialiken 2,  Ziwen Zheng 3,  Weiting Zhang 4,  Siqi Zhang 5,  Yawei Zheng 6,  Zeqi Sun 7,  Haitao Zhang 8,  Xiwu Yan 9,  Ming Liu 10,  Zhuyuan Fang 11
Affiliations

Affiliations

  • 1 Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China. Electronic address: fanyd002@163.com.
  • 2 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: 2249053127@qq.com.
  • 3 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: 812261955@qq.com.
  • 4 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: zzzhangweiting@163.com.
  • 5 Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address: 717817802@qq.com.
  • 6 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: villis77@outlook.com.
  • 7 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: szqdoct@163.com.
  • 8 Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: zht_nucm@163.com.
  • 9 Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China. Electronic address: yxwssg@126.com.
  • 10 Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address: liuming@njucm.edu.cn.
  • 11 Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Jiangsu Chinese Medicine Clinical Medicine Innovation Center for Hypertension, Nanjing, 210029, China; Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address: fangzhuyuan@njucm.edu.cn.
PMID: 39393558 DOI: 10.1016/j.jep.2024.118896
Abstract

Ethnopharmacological relevance: Qianyang Yuyin granules (QYYY) have been used clinically to treat hypertension for over two decades. Previous clinical trials have shown that QYYY can improve vascular elastic function in hypertensive patients. However, the underlying pharmacological mechanism is unclear.

Aim of the study: To elucidate the effects and mechanisms of QYYY on vascular remodeling using a multidisciplinary approach that includes network pharmacology, proteomics, and both in vitro and in vivo experiments.

Materials and methods: The main components of QYYY were identified using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Network pharmacology and molecular docking were employed to predict QYYY's primary active ingredients, potential therapeutic targets and intervention pathways in hypertensive vascular remodeling. We induced hypertension in male C57BL/6 mice by infusing angiotensin II (Ang II) via osmotic minipumps, and performed pre-treatment with QYYY or Sacubitril/valsartan (Entresto). Blood pressure was monitored in vivo, followed by the extraction of aortas to examine pathological structural changes and alterations in protein expression patterns. The expression and location of proteins involved in the HIF-1α/TWIST1/P-p65 signaling pathway were investigated, as well as markers of vascular smooth muscle cells (VSMCs) phenotypic switch. In vitro, we studied the effects of QYYY water extract on Ang II-stimulated human aortic VSMCs. We investigated whether QYYY could affect the HIF-1α/TWIST1/P-p65 signaling pathway, thereby ameliorating Apoptosis, Autophagy, and phenotype switch in VSMCs.

Results: We identified 62 main compounds in QYYY, combined with network pharmacology, speculated 827 potentially active substances, and explored 1021 therapeutic targets. The KEGG pathway analysis revealed that the mechanisms of action associated with QYYY therapy potentially encompass various biological processes, including metabolic pathways, TNF signaling pathways, Apoptosis, Ras signaling pathways, HIF-1 signaling pathways, autophagy-animal pathways. In hypertensive mice, QYYY restored abnormally elevated blood pressure, vascular remodeling, and inflammation with a dose-response relationship while altering abnormal protein patterns. In vitro, QYYY could inhibit abnormal proliferation, migration, intracellular CA2+ accumulation and cytoskeletal changes of VSMCs. It improved mitochondrial function, reduced ROS levels, stabilized membrane potential, prevented cell death, and reduced overproduction of TGF-β1, TNF-a, and IL-1β.

Conclusion: QYYY may be able to inhibit the overactivation of the HIF-1α/TWIST1/P-p65 signaling pathway, improve the phenotypic switch, and balance Apoptosis and Autophagy in VSMCs, thereby effectively improving vascular remodeling caused by hypertension.

Keywords

Hypertension; Phenotypic switch; Qianyang Yuyin granules; Vascular remodeling; Vascular smooth muscle cells.

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