Isosteviol reduces the acute inflammatory response after burns by upregulating MMP9 in macrophages leading to M2 polarization.

Isosteviol is a widely known sweetener isolated from the herb Stevia rebaudiana. It is well documented that isosteviol, a derivative of stevioside, has a variety of biological activities, including anti-inflammatory, anti-hypertensive, and cardioprotective effects and alleviation of ischaemia-reperfusion injury. However, the protective mechanism of isosteviol in burn injuryis still unclear. This work aimed to screen and identify the role of macrophage-related genes after burn injury through bioinformatic analysis and biological experiments and to detect the effect of isosteviol on burn inflammation. The results showed that two days after burn injury was considered the acute inflammatory response node, which was when the expression levels of CCL3, CCL4, MMP9, and CD86 in macrophages were significantly changed. Monitoring and regulating these sensitive indicators may help to evaluate the severity of burns and reduce the inflammatory impact of burns on the body. After treatment with isosteviol, during the acute inflammatory phase, the expression of MMP9 was increased, the polarization of macrophages towards the alternatively activated (M2) phenotype was increased, and IL-6 and TNF-α levels were significantly decreased. Our study provides evidence thatisosteviol can reduce inflammation after burn injury by promoting an increase in the M2-classically activated (M1) macrophage ratio and increasing the expression of MMP9 in burn wound tissue during acute inflammation.