Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an 710061, China.
Nutrients. 2022 Apr 22;14(9):1756. doi: 10.3390/nu14091756.
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.
原花青素 B2（PCB2）作为一种天然类黄酮，已被证实具有抗氧化和抗炎作用，可用于治疗肝脏疾病。越来越多的证据表明尼古丁具有肝毒性。然而，PCB2 是否能预防尼古丁引起的肝毒性以及其潜在的机制尚不清楚。在这里，我们报道尼古丁可促进肝实质细胞发生细胞焦亡，这表现在碘化丙啶（PI）阳性细胞数量增加、半胱氨酸天冬氨酸蛋白酶-1（Caspase-1）和 Gasdermin D（GSDMD）激活、NOD 样受体含pyrin 结构域 3（NLRP3）表达增强以及乳酸脱氢酶（LDH）、白细胞介素（IL）-1β和 IL-18 释放增加。用小干扰 RNA（siRNA）沉默 GSDMD 可有效抑制 LDH 释放和 IL-1β、IL-18 的分泌。此外，罗格列酮（RGZ）可预防尼古丁诱导的肝实质细胞焦亡。此外，我们发现 PCB2 通过激活肝实质细胞中的过氧化物酶体增殖物激活受体-γ（PPARγ）来减轻尼古丁诱导的细胞焦亡。此外，给予 PCB2 可改善尼古丁处理小鼠的肝损伤和肝实质细胞焦亡。因此，我们的研究结果表明，PCB2 通过依赖 PPARγ 的方式减轻细胞焦亡和肝损伤。我们的研究结果表明，PCB2 通过依赖 PPARγ 的方式发挥其肝脏保护作用。
