Herbacetin attenuates lipopolysaccharide-induced inflammatory lung injury in mice by inhibiting Fth1hi neutrophil aggregation and accelerating its clearance

The aim of this study was to systematically investigate the protective effect of Herbacetin (Her) against lipopolysaccharide (LPS)-induced inflammatory lung injury and its related mechanisms. Firstly, a mouse model of inflammatory lung injury was successfully constructed by intratracheal drip injection of LPS, and its protective effect on mice with inflammatory lung injury was evaluated by observing the overall lung tissue morphology changes, lung histopathological injury, lung wet-to-dry weight ratio, lung organ coefficients, total proteins, and inflammatory factor contents. The results showed that administration of Her treatment improved LPS-induced lung histopathological injury, reduced lung tissue edema, decreased the content of pro-inflammatory factors TNF-α, IL-6 and IL-1β, and reduced the number of inflammatory cells. Meanwhile, our results also showed that two neutrophil populations (Fth1hi Neu and Prok2hi Neu) in two different locations existed in the lung tissues of mice with LPS-induced inflammatory lung injury, and that LPS stimulation promoted the aggregation of Fth1hi Neu and the release of pro-inflammatory factors in the lung tissues, which was accompanied by a decrease in the content of the anti-inflammatory factor IL-10. Administration of Her treatment increased the content of the anti-inflammatory factor IL-10 in lung tissues, promote apoptosis and clearance of Fth1hi Neu, reduce the aggregation of Fth1hi Neu in lung tissues, and ameliorate the inflammatory injury of lung tissues. In conclusion, Her had a significant protective effect on LPS-induced inflammatory lung injury in mice, and its mechanism of action was related to elevating IL-10 levels and reducing Fth1hi Neu accumulation.