Lonicerin protects pancreatic acinar cells from caerulein-induced apoptosis, inflammation, and ferroptosis by activating the SIRT1/GPX4 signaling pathway

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2024-11-01 DOI:10.1016/j.taap.2024.117136

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引用次数: 0

Abstract

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.

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忍冬藤素通过激活SIRT1/GPX4信号通路，保护胰腺尖叶细胞免受caerulein诱导的凋亡、炎症和铁中毒的影响。

急性胰腺炎（AP）是一种常见的以胰腺炎症为特征的消化系统急症。据报道，忍冬藤素（LCR）在多种炎症性疾病中具有抗炎和免疫调节作用。然而，它在胰腺炎中的作用和机制仍然未知。本研究旨在探索 LCR 在 AP 中的保护作用和潜在机制。在这项研究中，LCR和铁前列素-1减轻了麦角新碱（CAE）暴露诱导的细胞毒性并降低了AR42J细胞的存活率，但麦角新碱加重了CAE暴露诱导的细胞毒性并降低了AR42J细胞的存活率。LCR对CAE处理的AR42J细胞具有保护作用，这体现在减轻了细胞凋亡、炎症和铁变态反应。从机理上讲，在 CAE 处理的 AR42J 细胞中，LCR 降低了核因子卡巴 B p65 的磷酸化水平，提高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，功能拯救实验表明，敲除 SIRT1 可部分抵消 LCR 对 CAE 诱导的 AR42J 细胞凋亡、炎症和铁变态反应的抑制作用。总之，LCR能减轻CAE暴露的AR42J细胞的凋亡、炎症和铁变态反应，这与SIRT1/GPX4信号通路的激活有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.