2. Academic Validation
  3. Carnosol attenuates Ang II-induced renal injury by p62-KEAP1-NRF2 signaling pathway

Carnosol attenuates Ang II-induced renal injury by p62-KEAP1-NRF2 signaling pathway

  • Toxicol Appl Pharmacol. 2025 Aug 21:504:117528. doi: 10.1016/j.taap.2025.117528.
Shijie Fan 1,  Ying Zhao 1,  Qingqing Zhao 1,  Diyun Xu 2,  Xi Chen 3,  Jibo Han 4,  Ziming Fang 2,  Guang Liang 5,  Yunjie Zhao 6
Affiliations

Affiliations

  • 1 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Department of Pharmacology, School of Medicine, Taizhou University, Taizhou, Jiaojiang, 318000, Zhejiang, China.
  • 4 Department of Cardiology, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
  • 5 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, China. Electronic address: wzmcliangguang@163.com.
  • 6 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: aabye1100@aliyun.com.
PMID: 40848917 DOI: 10.1016/j.taap.2025.117528
Abstract

Hypertension engenders numerous complications, including hypertensive renal disease (HRD). Recent studies have underscored the significance of redox homeostasis in hypertension-associated kidney disorders. Carnosol (Car) has been identified as a potent antioxidant in Other Diseases. Nevertheless, its role in HRD remains uncertain. This research evaluated the therapeutic impact of Car on HRD and explored its pharmacological mechanism. Car (40 mg/kg) effectively ameliorated kidney injury and oxidative stress (OS) induced by angiotensin II (Ang II) both in vitro and in vivo. Mechanistically, Car facilitates the phosphorylation of p62 through its interaction with mTOR, leading to the degradation of KEAP1, the release of NRF2, and the subsequent upregulation of antioxidant genes. Blocking mTORC1 eliminated Car-induced p62 activation and its antioxidant functions. In summary, our research has demonstrated that Car activates the p62-KEAP1-NRF2 pathway to alleviate the kidney injury and OS caused by Ang II. Consequently, Car may emerge as a promising candidate for the prevention and treatment of Ang II-induced kidney injury.

Keywords

Carnosol; Hypertensive renal disease; Oxidative stress; p62-KEAP1-NRF2.

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