The Protective Effect of Pilose Antler Peptide on CUMS-Induced Depression Through AMPK/Sirt1/NF-κB/NLRP3-Mediated Pyroptosis

• DOI: 10.3389/fphar.2022.815413
• Publication Date: 2022-03-28T22:38:29Z
• Authors: Yue Hu; Min Zhao; Tong Zhao; Mingming Qi; Guangda Yao; Yu Dong
• Keywords: Pyroptosis

Background: Pilose antler peptide (PAP), prepared from the pilose of Cervus nippon Temminck, is widely used in traditional Chinese medicine (TCM) against various inflammatory disorders. TCM prescriptions containing are often prescribed clinically to treat depression. However, pharmacological mechanisms how PAP, inflammation, prevents and treats depression remain poorly understood. Methods: PAP was identified by de novo sequencing database searching. Then, behavioral tests were conducted investigate effect on CUMS-exposed mice. In parallel, Nissl staining Golgi-Cox for exploring neural cells dendritic spine density. Additionally, expression key proteins AMPK/Sirt1/NF-κB/NLRP3 pathway analyzed Western blot. Finally, CUMS procedure 6 weeks. At 5th week, fluoxetine (Flu) intragastrically treated 2 The silencing information regulator-related enzyme 1 (Sirt1) inhibitor EX-527 AMP-activated protein kinase (AMPK) dorsomorphin employed effects Sirt1 AMPK PAP-mediated Results: attenuated behavior alteration caused stimulation, decreased number neurons, restored treatment effectively upregulated expressions p-AMPK suppressed Ac-NF-κB, NLRP3, Ac-Caspase-1, GSDMD-N, Cleaved-IL-1β, Cleaved-IL-18. Moreover, selectively inhibited able compromise therapeutic Conclusion: present work indicated that has a protective CUMS-induced addition, played critical roles PAP-relieved might be potential option treating