堇青碱通过与 PSMA2 结合并减轻胰腺纤维化来保护慢性胰腺炎。

IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Journal of Gastroenterology Pub Date : 2024-11-01 Epub Date: 2024-08-15 DOI:10.1007/s00535-024-02145-4
Pengyuan Wang, Bangwei Huang, Yu Liu, Xin Tan, Libo Liu, Baoru Zhang, Zhaoshen Li, Le Kang, Lianghao Hu
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引用次数: 0

摘要

背景:胰腺纤维化是慢性胰腺炎的主要病理特征:胰腺纤维化是慢性胰腺炎的主要病理特征。目前尚缺乏有效缓解或逆转胰腺纤维化从而治愈慢性胰腺炎的药物:方法:我们从80种中药单体中筛选出能缓解胰腺纤维化的药物,并验证了其疗效和机制:结果:通过对80个化合物的药物筛选,我们初步确定了堇青碱作为抗胰腺纤维化的候选药物。在体外,堇青碱能剂量依赖性地减少 TGF-β1 诱导的胰腺星状细胞胶原 I 的合成,并抑制其活化。此外,我们还发现,可可碱能减轻慢性胰腺炎小鼠的形态学破坏,如针叶细胞萎缩、胶原沉积等,并减轻胰腺重量。我们进一步在 mRNA 和蛋白质水平上验证了堇青碱的抗纤维化作用。我们还发现,在体外和体内,鸡矢藤碱都能抑制 NF-κB 信号通路。接着,我们通过 Lip-SMap 鉴定出 PSMA2 是可可碱的结合蛋白,并用 DARTS 进行了验证。此外,PSMA2的siRNA破坏了corynoline的抗纤维化作用:总之,可可碱是一种治疗胰腺纤维化和慢性胰腺炎的有效药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis.

Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis.

Background: Pancreatic fibrosis is the main pathological feature of chronic pancreatitis. There is a lack of medications that effectively alleviate or reverse pancreatic fibrosis and thus cure chronic pancreatitis.

Methods: We screened drugs that could alleviate pancreatic fibrosis from 80 traditional Chinese medicine monomers and verified their efficacy and mechanisms.

Results: We preliminarily identified corynoline as an antifibrotic candidate by drug screening among 80 compounds. In vitro, corynoline dose-dependently reduces collagen I synthesis in pancreatic stellate cells induced by TGF-β1 and inhibits its activation. Furthermore, we found that corynoline could alleviate the morphological disruption, such as acinar cell atrophy, collagen deposition etc., as well as reduced pancreatic weight in mice with chronic pancreatitis. We further validated the antifibrotic effect of corynoline in mRNA and protein levels. We also found that corynoline could inhibit NF-κB signaling pathway in vitro and in vivo. Next, we identified PSMA2 as the binding protein of corynoline by Lip-SMap and validated it using DARTS. Moreover, the siRNA of PSMA2 disrupts the anti-fibrotic effect of corynoline.

Conclusion: In conclusion, corynoline is a promising agent for the treatment of pancreatic fibrosis and chronic pancreatitis.

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来源期刊
Journal of Gastroenterology
Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
12.20
自引率
1.60%
发文量
99
审稿时长
4-8 weeks
期刊介绍: The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.
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