2. Academic Validation
  3. Harmine derivative H-2-168 induces the death of Echinococcus granulosus by regulating mitochondrial fusion and fission

Harmine derivative H-2-168 induces the death of Echinococcus granulosus by regulating mitochondrial fusion and fission

  • Pharm Biol. 2025 Dec;63(1):188-200. doi: 10.1080/13880209.2025.2485898.
Yuehong Gong 1 2 3,  Meiling Zhao 4,  Meichi Pan 4,  Yicong Zhao 4,  Junpeng Liu 5,  Hao Wen 2,  Jianhua Wang 1 2 3
Affiliations

Affiliations

  • 1 Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • 2 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Clinical Drug Research, Urumqi, China.
  • 4 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China.
  • 5 Department of Medicine, School of Pharmacy, Xinjiang Medical University, Urumqi, China.
PMID: 40188381 DOI: 10.1080/13880209.2025.2485898
Abstract

Context: H-2-168 has pharmacological effects similar to those of harmine, with less toxicity. The health of cells and organisms depends on a delicate balance between mitochondrial fusion and fission.

Objective: This study investigated the roles of H-2-168 and mitochondrial fusion and fission in Echinococcus granulosus.

Materials and methods: Notably, E. granulosus were isolated from fresh sheep livers, and then treated with H-2-168 (25 μg/mL), mitochondrial division inhibitor 1 (Mdivi-1, 25 μg/mL) or the combination of H-2-168:Mdivi-1 (25 μg/mL:12.5 μg/mL). After 24 h of culture, the indices related to E. granulosus were measured. Additionally, Drp1 was knocked down to explore its effects on E. granulosus growth.

Results: The EC50 values of H-2-168, Mdivi-1 and H-2-168:Mdivi-1 against E. granulosus were 44.171, 117.882 and 32.924 μg/mL, respectively. Compared with H-2-168 or Mdivi-1, the combination of H-2-168 and Mdivi-1 showed better inhibitory effects on E. granulosus viability, as well as increased levels of ROS and LDH, decreased ATP levels, inhibited mitochondrial activity and reduced mitochondrial membrane potential (p < 0.05), with the upregulation of Caspase-3, Cyt-c, Drp1, Fis1 and downregulation of Bcl-2, Mfn2 and OPA1. Additionally, Drp1 knockdown was successfully performed in E. granulosus, which significantly inhibited E. granulosus viability (p < 0.05) and further downregulated Mfn2 expression induced by H-2-168.

Discussion and conclusion: Drp1 is closely associated with mitochondrial fusion and fission, and H-2-168 may promote E. granulosus death through disrupting the balance between mitochondrial fusion and fission.

Keywords

Cystic echinococcosis; Drp1; E. granulosus; mitochondria; viability.

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