Department of Emergency, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Department of Obstetrics, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Toxicol Appl Pharmacol. 2024 Nov;492:117136. doi: 10.1016/j.taap.2024.117136. Epub 2024 Oct 29.
Acute pancreatitis (AP) is a familiar emergency of digestive system characterized by pancreatic inflammation. Lonicerin (LCR) has been reported to exert anti-inflammatory and immunomodulatory characteristics in several inflammatory diseases. Nevertheless, its role and mechanism involved in AP are still unknown. This study was designed to explore the protective effect and potential mechanism of LCR in AP. In this study, LCR and ferrostatin-1 alleviated, but erastin aggravated caerulein (CAE) exposure-induced cytotoxicity and reduction of cell viability in AR42J cells. LCR exhibited a protective role in CAE-treated AR42J cells, as evidenced by alleviation of apoptosis, inflammation, and ferroptosis. Mechanistically, LCR decreased the phosphorylation level of nuclear factor-kappa B p65 and increased the levels of silent information regulator 1 (SIRT1) and glutathione peroxidase 4 (GPX4) in CAE-treated AR42J cells. Furthermore, functional rescue experiments manifested that knockdown of SIRT1 partially negated the inhibitory action of LCR against CAE-induced apoptosis, inflammation, and ferroptosis in AR42J cells. Overall, LCR mitigates apoptosis, inflammation, and ferroptosis in CAE-exposed AR42J cells, which is related to the activation of the SIRT1/GPX4 signaling pathway.
急性胰腺炎（AP）是一种常见的消化系统急症，其特征为胰腺炎症。水苏碱（LCR）已被报道在几种炎症性疾病中具有抗炎和免疫调节作用。然而，其在 AP 中的作用和机制尚不清楚。本研究旨在探讨 LCR 在 AP 中的保护作用及其潜在机制。在本研究中，LCR 和 ferrostatin-1 减轻了，但 erastin 加重了 CAE 暴露诱导的 AR42J 细胞的细胞毒性和细胞活力降低。LCR 在 CAE 处理的 AR42J 细胞中表现出保护作用，表现在减轻细胞凋亡、炎症和铁死亡。机制上，LCR 降低了 CAE 处理的 AR42J 细胞中核因子-κB p65 的磷酸化水平，增加了沉默信息调节因子 1（SIRT1）和谷胱甘肽过氧化物酶 4（GPX4）的水平。此外，功能挽救实验表明，SIRT1 的敲低部分否定了 LCR 对 AR42J 细胞中 CAE 诱导的细胞凋亡、炎症和铁死亡的抑制作用。总之，LCR 减轻了 CAE 暴露的 AR42J 细胞中的细胞凋亡、炎症和铁死亡，这与 SIRT1/GPX4 信号通路的激活有关。
