2. Academic Validation
  3. Dihydromyricetin treats pulmonary hypertension by modulating CKLF1/CCR5 axis-induced pulmonary vascular cell pyroptosis

Dihydromyricetin treats pulmonary hypertension by modulating CKLF1/CCR5 axis-induced pulmonary vascular cell pyroptosis

  • Biomed Pharmacother. 2024 Nov:180:117614. doi: 10.1016/j.biopha.2024.117614.
Qian Yan 1,  Ping Li 2,  Shasha Liu 3,  Yang Sun 1,  Chen Chen 4,  Junpeng Long 1,  Yuting Lin 1,  Jinping Liang 1,  Hanlong Wang 1,  Ling Zhang 1,  Hongbin Wang 1,  Huiqin Wang 1,  Songwei Yang 1,  Meiyu Lin 1,  Xuan Liu 1,  Jiao Yao 1,  Zhifeng Tian 1,  Naihong Chen 5,  Yantao Yang 6,  Qidi Ai 7
Affiliations

Affiliations

  • 1 Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
  • 2 Technology Innovation Center, Hunan University of Chinese Medicine, Changsha 410208, China.
  • 3 Department of Pharmacy, Changsha Hospital for Matemal&Child Health Care Affiliated to Hunan Normal University, Changsha 410007, China.
  • 4 Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China.
  • 5 Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: chennh@imm.ac.cn.
  • 6 Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: xdyyt1@163.com.
  • 7 Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: 278339420@qq.com.
PMID: 39461017 DOI: 10.1016/j.biopha.2024.117614
Abstract

Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by elevated pulmonary artery pressure and vascular remodeling, resulting in poor prognosis and increased mortality rates. Chemokine-like factor 1 (CKLF1) plays a significant role in inducing inflammation and cell proliferation, both of which are critical processes in the pathogenesis of various diseases. Dihydromyricetin (DMY) has garnered attention for its potent anti-inflammatory properties. This study evaluated the protective effects of DMY against PH, demonstrating that DMY treatment can mitigate Pyroptosis in pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) in vivo via the CKLF1/CCR5 axis. Results indicated significant improvements in hemodynamics, inflammatory responses, fibrosis, vascular remodeling, and right ventricular hypertrophy in PH rats following DMY treatment. Furthermore, the interaction between CKLF1 and CCR5 was investigated in CKLF1-/- rats after PH induction. DMY was found to downregulate CKLF1 expression and the inflammatory response in the lungs, with its therapeutic efficacy diminished following CKLF1 knockdown. This study underscores the therapeutic potential of DMY in the management of PH and lays a foundation for future research and clinical applications.

Keywords

CKLF1/CCR5 axis; Dihydromyricetin; Pulmonary hypertension; Pyroptosis.

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