Narciclasine alleviates zearalenone-induced focal adhesion damage and anoikis in rat Sertoli cells through PI3K signaling pathway
- Phytomedicine. 2026 Jul:156:158218. doi: 10.1016/j.phymed.2026.158218.
- 1. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Zhaoqing High-level Talents Training and Development Center, Zhaoqing, China.
- 2. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Xinyang Agriculture and Forestry University, Henan, 464000, Xinyang, China.
- 3. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China.
- 4. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.
- 5. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. Electronic address: [email protected].
Background: Zearalenone (ZEA), a widespread mycotoxin found in crops, is known to cause reproductive disorders in human and Animals.
Purpose: This study investigated how zearalenone (ZEA) disrupts focal adhesion in Sertoli cells (SCs) and testicular tissue, thereby inducing anoikis. We also examined the protective effect of narciclasine, which we found acts by preserving focal adhesion integrity via the PI3K/Akt signaling pathway.
Study design: In this study, we examined how ZEA affects focal adhesions as well as anoikis in Sertoli cells (SCs) and cells of testicular tissue.
Methods: SCs were treated with varying concentrations of ZEA. Results showed that ZEA reduced focal adhesions, weakened cell adhesion, and induced anoikis in SCs. Notably, Narciclasine (NAR) attenuated the ZEA-induced suppression of the PI3K signaling pathway. Furthermore, NAR restored focal adhesion structure, enhanced cell adhesion, and reduced anoikis via PI3K signaling. In vivo experiments demonstrated that NAR effectively reversed ZEA-induced testicular dysplasia and pathological damage. NAR also mitigated focal adhesion loss and reduced Apoptosis in testicular tissue through the PI3K pathway.
Conclusion: This study provides new insights into the molecular mechanisms of ZEA-induced cytotoxicity in Sertoli cells and testicular injury, and identifies NAR as a potential therapeutic agent against ZEA-mediated testicular damage.