Puerarin attenuates lipopolysaccharide-induced myocardial injury via the 14-3-3γ/PKCε pathway activating adaptive autophagy

•Puerarin (Pue) pretreatment protected the myocardium against LPS injury.•Pue pretreatment activated adaptive autophagy by upregulating 14–3-3γ and impelling PKCε to mitochondria.•Protective mechanism of Pue may be associated with inhibited oxidative stress and inflammatory cytokine activities. Studies have confirmed that the heart is the main target organ of lipopolysaccharide (LPS) attacks, and 14–3-3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is the major bioactive ingredient isolated from the root of Pueraria lobata. It possesses many pharmacological properties, which has been widely used in the treatment and adjuvant therapy of cardio- and cerebrovascular diseases and cancer, etc. The study intended to explore the effects and mechanism of Pue pretreatment to protect myocardium against LPS injury. Adult mice and primary cultured neonatal rat cardiomyocytes were pretreated with Pue, and the injury model was made with LPS. Results showed that Pue pretreatment alleviated LPS-induced injury, as demonstrated by increased cell viability, decreased LDH activity and apoptosis, inhibited excess oxidative stress and the inflammatory cytokine release, and maintained mitochondrial function. Furthermore, Pue pretreatment upregulated 14–3-3γ expression, interacted with PKCε, which was phosphorylated and impelled migration to mitochondria, and then activated adaptive autophagy and protected the myocardium. However, pAD/14–3-3γ-shRNA or 3-MA (an autophagy inhibitor) could weaken the above effects of Pue pretreatment. Together, Pue pretreatment could activate adaptive autophagy by the 14–3-3γ/PKCε pathway and protect the myocardium against LPS injury.