Procyanidin B2 Attenuates Nicotine-Induced Hepatocyte Pyroptosis through a PPARγ-Dependent Mechanism

Abstract

Procyanidin B2 (PCB2), a natural flavonoid, has been demonstrated to exert anti-oxidation and anti-inflammatory effects on hepatic diseases. Increasing evidence shows the hepatoxicity of nicotine. However, whether PCB2 protects against nicotine-induced hepatoxicity and the underlying mechanisms remains uncharacterized. Here, we reported that nicotine promoted hepatocyte pyroptosis, as evidenced by the elevation of propidium iodide (PI)-positive cells, the activation of Caspase-1 and gasdermin D (GSDMD), the enhanced expression of NOD-like receptor containing pyrin domain 3 (NLRP3) and the increased release of lactate dehydrogenase (LDH), interleukin (IL)-1β and IL-18. The silencing of GSDMD by small interfering RNA (siRNA) efficiently inhibited the release of LDH and the secretion of IL-1β and IL-18. In addition, rosiglitazone (RGZ) prevented hepatocyte pyroptosis induced by nicotine. Furthermore, we showed that PCB2 attenuated nicotine-induced pyroptosis through the activation of peroxisome proliferator-activated receptor-γ (PPARγ) in hepatocytes. Moreover, administration of PCB2 ameliorated liver injury and hepatocyte pyroptosis in nicotine-treated mice. Hence, our findings demonstrated that PCB2 attenuated pyroptosis and liver damage in a PPARγ-dependent manner. Our results suggest a new mechanism by which PCB2 exerts its liver protective effects.