2. Academic Validation
  3. GSK3β/HIF-1α signaling-dependent anti-parasite effect of Cynanchi atrati Radix

GSK3β/HIF-1α signaling-dependent anti-parasite effect of Cynanchi atrati Radix

  • iScience. 2025 Dec 1;29(1):114292. doi: 10.1016/j.isci.2025.114292.
Fei-Fei Gao 1 2 3,  Guan-Hao Hong 4 5,  Xin-Cheng Wang 4 5,  Jia-Hui Zeng 2,  Yu-Sun Yun 4 5,  In-Wook Choi 5,  Jae-Min Yuk 4 5,  Wei Zhou 6,  Xin-Tian Chen 3 7,  Gang Min Hur 8,  Guang-Ho Cha 4 5
Affiliations

Affiliations

  • 1 Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.
  • 2 Laboratory of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.
  • 3 Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Zhanjiang 524001, Guangdong, China.
  • 4 Brain Korea 21 FOUR Project for Medical Science, Chungnam National University College of Medicine, Daejeon 301-131, Korea.
  • 5 Department of Medical Science and Department of Infection Biology, Chungnam National University, College of Medicine, Daejeon 301-131, Korea.
  • 6 Biotissue Repository, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.
  • 7 Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.
  • 8 Department of Pharmacology, Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
PMID: 41509906 DOI: 10.1016/j.isci.2025.114292
Abstract

Medicinal Plants yield bioactive compounds with potential for Parasite control. We examined Cynanchi atrati Radix (C. atrati) and its component 4'-hydroxyacetophenone (4'HAP) for activity against Toxoplasma gondii (T. gondii) using cultured cells and mouse Infection models. C. atrati extracts limited Parasite growth with minimal host-cell toxicity. Chemical screening pinpointed 4'HAP as the active constituent that suppresses T. gondii proliferation in vitro and in vivo. Mechanistically, C. atrati and 4'HAP activated GSK3β, destabilized HIF-1α, and curtailed Parasite fitness; pharmacologic GSK3β inhibition restored Parasite growth, whereas HIF-1α depletion further reduced survival, highlighting the GSK3β/HIF-1α axis as a host pathway that constrains Infection. These results identify a plant-derived small molecule and its mechanistic target for host-directed antiparasitic therapy and provide a framework for developing treatments for toxoplasmosis.

Keywords

microbial metabolism; microbiology parasite; parasitology.

Figures
Products