2. Academic Validation
  3. Z-Ligustilide restricts rabies virus replication by inducing ferroptosis through the ACSL4-LPCAT3-POR pathway

Z-Ligustilide restricts rabies virus replication by inducing ferroptosis through the ACSL4-LPCAT3-POR pathway

  • Vet Microbiol. 2024 Sep 23:298:110260. doi: 10.1016/j.vetmic.2024.110260.
Jianqing Zhao 1,  Qianruo Wang 2,  Zhenkun Liu 1,  Meixin Sun 1,  Rui Zhou 1,  Zhen F Fu 1,  Ling Zhao 3,  Ming Zhou 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.
  • 2 State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
  • 3 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China. Electronic address: lingzhao@mail.hzau.edu.cn.
  • 4 National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China. Electronic address: mingzhou@mail.hzau.edu.cn.
PMID: 39316946 DOI: 10.1016/j.vetmic.2024.110260
Abstract

Rabies, induced by rabies virus (RABV), still threaten global health all over the world, and no effective therapy is available for rabies currently. Recently, a series of natural plant components have been found to inhibit virus production. In this study, Z-Ligustilide, a natural component of Ligusticum chuanxiong Hort, was found to inhibit RABV replication. Initially, the concentration of cytotoxicity 50 % (CC50) of Z-Ligustilide in N2a and BSR cells were 429.9 μM and 335.5 μM, respectively, which both significantly restrict RABV production in a concentration-dependent manner. Moreover, Z-Ligustilide was found to mainly inhibit the replication stage of RABV. Specifically, Z-Ligustilide can suppress lipid droplet (LD) formation via directly inhibiting diacylglycerol Acyltransferase 1/2 (DGAT1/2) expression, which can further promote cellular lipid peroxidation, Fe2+ concentration, Reactive Oxygen Species (ROS), and induce Ferroptosis ultimately. Furthermore, Z-Ligustilide was demonstrated to increase Ferroptosis via Acyl-CoA synthetase long-chain family member 4 (ACSL4)- Lysophosphatidylcholine Acyltransferase 3 (LPCAT3)- Cytochrome P450 Oxidoreductase (POR) pathway. Above all, this study explored the Antiviral function of Z-Ligustilide, which provides a novel insight for developing anti-RABV drugs.

Keywords

Diacylglycerol acyltransferase; Ferroptosis; Lipid droplets; Rabies virus; Z-Ligustilide.

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