Forsythiaside A attenuates mastitis via PINK1/Parkin-mediated mitophagy

•FTA exerts a protective function on mastitis via modulating mitophagy medicated by PINK1/Parkin signaling pathway.•FTA has the ability to enhance mitophagy, diminish cellular and mitochondrial reactive oxygen species (ROS) generation, and mitigate mitochondrial impairment, alleviate mastitis.•This discovery offers novel insights into identifying therapeutic targets for mastitis in dairy cows. Additionally, FTA could potentially serve as a tailored regulator of mitophagy, so introducing a fresh perspective on the prevention and treatment of bovine mastitis. Bovine mastitis is the most common animal production disease in the global dairy industry, which affects the health of dairy cows. When bovine mastitis occurs, the mitochondrial metabolism of breast tissue increases, and the relationship between inflammation and mitophagy has become a hot topic for many scholars. The abuse of antibiotics leads to the increase of resistance to bovine mastitis. FTA is one of the main effective components of Forsythia suspensa, which has anti-inflammatory, anti-infection, anti-oxidation and anti-virus pharmacological effects, and has broad application prospects in the prevention and treatment of bovine mastitis. However, the relationship between the anti-inflammatory effects of FTA and mitophagy is still unclear. This study mainly explores the anti-inflammatory effect of FTA in bovine mastitis and the relationship between mitophagy. MAC-T cells and wild-type mice were used to simulate the in vitro and in vivo response of mastitis. After the pretreatment with FTA, CsA inhibitors and siPINK1 were used to interfere with mitophagy, and the mitochondrial function impairment and the expression of inflammatory factors were detected. It was found that pre-treatment with FTA significantly reduced LPS induced inflammatory response and mitochondrial damage, while promoting the expression of mitophagy related factors. However, after inhibiting mitophagy, the anti-inflammatory effect of FTA was inhibited. This study is the first to suggest the relationship between the anti-inflammatory effect of FTA and mitophagy. PINK1/Parkin-mediated mitophagy is one of the ways that FTA protects MAC-T cells from LPS-induced inflammatory damage.