AUTHOR=Chen Hanze , Xu Xinxin , Tang Qiwen , Ni Linhui , Cao Shuxia , Hao Yonggang , Wang Li , Hu Xingyue 

TITLE=(+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1023450

DOI=10.3389/fphar.2022.1023450

ISSN=1663-9812

ABSTRACT=<p><bold>Background and purpose:</bold> Neutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis.</p><p><bold>Methods:</bold> Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis <italic>in vitro</italic>. Neutrophils treated with (+)-borneol at three different time points (−30 min, 0, and 30 min) associated with PMA stimulation were used to examine the effect of (+)-borneol on the formation of NETs. The ROS generation of neutrophils was also measured to explore the potential mechanism of the inhibitory effect of (+)-borneol on NETosis.</p><p><bold>Results:</bold> (+)-Borneol pretreatment inhibited NETosis induced by PMA. Immunofluorescence staining visualized and confirmed the inhibitory effect. (+)-Borneol inhibited the burst of ROS in neutrophils caused by PMA. Suppressing NADPH oxidase or protein kinase C (PKC) eliminated the effect of (+)-borneol on NETosis. Moreover, inhibiting Toll-like receptor 2 (TLR2) led to increased NETosis which can be inhibited by (+)-borneol.</p><p><bold>Conclusion:</bold> (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation <italic>in vitro</italic>. (+)-Borneol therapy may be effective in some NET-dependent conditions.</p>