Patchouli alcohol from Pogostemon cablin Benth inhibits H1N1 infection by repressing inflammasome and proptosis by targeting ubiquitin specific peptidase 18

Abstract

Influenza virus infection can cause lung inflammation and viral pneumonia in patients. Patchouli alcohol (PA), a tricyclic sesquiterpene derived from Pogostemonis Herba, has been shown to alleviate inflammation in various diseases. However, the molecular mechanism by which patchouli exerts its anti-inflammatory effects, particularly its role in mitigating influenza virus induced inflammation and pneumonia during H1N1 viral infection, remains largely unclear. Herein, we found that PA considerably reduced body weight loss, lung pathological index and attenuated lung histological damage in H1N1-infected mice. Mechanistically, PA reduced the production and secretion of inflammatory cytokines via inhibition of the NF-κB-signaling pathway and blocking inflammasome-mediated proptosis. Additionally, proteomic analysis identified several potential targets of PA, with ubiquitin-specific peptidase 18 (USP18) emerging as a key candidate. Further investigation revealed that PA binds to USP18, enhancing its stability and increasing its transcriptional and translational expression. Overall, our results emphasize the anti-inflammatory effects of PA during influenza virus infection. PA may alleviate lung inflammation and damage by targeting USP18, offering a potential therapeutic strategy for treating influenza-induced lung complications.

Keywords: Inflammasome; Influenza virus; Patchouli alcohol.