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

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

doi:10.3389/fphar.2022.1023450

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

Front Pharmacol. 2022 Nov 7:13:1023450. doi: 10.3389/fphar.2022.1023450. eCollection 2022.

Authors

Hanze Chen¹, Xinxin Xu¹, Qiwen Tang¹, Linhui Ni¹, Shuxia Cao¹, Yonggang Hao², Li Wang¹, Xingyue Hu¹

Affiliations

¹ Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.

Abstract

Background and purpose: 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. Methods: Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis in vitro. 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. Results: (+)-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. Conclusion: (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation in vitro. (+)-Borneol therapy may be effective in some NET-dependent conditions.

Keywords: antioxidant; borneol; inflammation; neutrophil extracellular traps; reactive oxygen species.