2. Academic Validation
  3. Carnosol mitigates Ang II-stimulated vascular injury and oxidative stress by directly binding to FAK and inhibiting its activation

Carnosol mitigates Ang II-stimulated vascular injury and oxidative stress by directly binding to FAK and inhibiting its activation

  • Inflammopharmacology. 2025 Jun;33(6):3349-3362. doi: 10.1007/s10787-025-01721-1.
Yucheng Jiang # 1 2,  Zhaozheng Zheng # 1 2,  JunYi Wang 2,  Yingjie Liao 2,  Zhihan Jia 1 2,  Wante Lin 1 2,  Diyun Xu 1 2,  Jiong Wang 2,  Gaojun Wu 3,  Guang Liang 4 5 6,  Bozhi Ye 7 8 9
Affiliations

Affiliations

  • 1 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. gaojunwuwyyy@163.com.
  • 4 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. wzmcliangguang@163.com.
  • 5 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. wzmcliangguang@163.com.
  • 6 School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, China. wzmcliangguang@163.com.
  • 7 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. fredye2012@163.com.
  • 8 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. fredye2012@163.com.
  • 9 School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, China. fredye2012@163.com.
  • # Contributed equally.
PMID: 40146440 DOI: 10.1007/s10787-025-01721-1
Abstract

Vascular injury is a serious complication associated with hypertension, for which effective treatments are currently lacking. Oxidative stress serves as the primary pathophysiological mechanism underlying hypertension-induced vascular injury. Carnosol, an extract derived from rosemary, has garnered increasing interest because of its well-established antioxidant properties. However, its potential therapeutic effect on vascular injury remains unclear. This study investigated the therapeutic potential of carnosol in angiotensin II-stimulated vascular injury and elucidated its underlying mechanisms of action. C57BL/6J mice were subjected to vascular injury through the subcutaneous implantation of a micropump filled with Ang II, followed by the intragastric administration of carnosol for four weeks. Carnosol ameliorated Ang II-stimulated vascular dysfunction and remodeling in a dose-dependent manner. Mechanistically, carnosol exerted an inhibitory effect on oxidative stress in the vascular tissue and HUVECs by regulating the PI3K/Akt pathway. Furthermore, we revealed that FAK, which received the highest target score in the molecular docking analysis, could directly bind to carnosol in both cellular models and human aortic tissues. Additionally, carnosol inhibited the phosphorylation of FAK, thereby reducing oxidative stress levels in HUVECs. Notably, when PND-1186 was administered to inhibit the phosphorylation of FAK, carnosol was no longer able to modulate the PI3K/Akt signaling pathway. In conclusion, we showed that carnosol can inhibit the PI3K/Akt signaling pathway by binding to the FAK protein and reducing its phosphorylation, thereby improving Ang II-stimulated vascular injury.

Keywords

Angiotensin II; Carnosol; FAK; Oxidative stress; Vascular injury.

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