Cyanidin-3-galactoside from Aronia melanocarpa ameliorates PM10-induced pulmonary inflammation by promoting PINK1/Parkin signaling pathway-mediated alveolar macrophage mitophagy

Abstract

Aronia melanocarpa is rich in anthocyanin, among which cyanidin-3-galactoside (C3G) is the most abundant. Here, we established an experimental model of mice and alveolar macrophage cell line MH-S exposed to PM10, and C3G was administered to explore the underlying mechanism of C3G exerting protective effects on PM10-induced lung inflammation. The results showed C3G alleviated PM10-induced lung inflammation by reducing matrix metalloproteinases production at both gene and protein levels as well as pro-inflammatory cytokine levels. Autophagy was activated in PM10-injured alveolar macrophages (AMs), and C3G promoted autophagy indicated by LC3, BECN1, Atg5, Bcl-2, and P62 expression, and C3G further resisted PM10-induced AMs apoptosis. Besides, C3G could promote Pink1/Parkin-mediated mitochondrial autophagy of AMs to alleviate the overexpression of mitochondrial reactive oxygen species (ROS) so that maintain mitochondrial membrane potential and ATP productions to restrict the distribution of Cyt-c and further reduce the increasing of caspase 3/7 activity. Therefore, C3G enhanced the clearance of PM10-damaged mitochondria by promoting AMs mitophagy, thereby reducing the activation of mitochondria-dependent apoptosis pathway and the production of excess ROS, which reduced AMs apoptosis and secretion of pro-inflammatory factors to ameliorate PM10-induced pulmonary inflammation, suggesting that C3G may be as a functional food ingredient with the potential to improve lung health.