方奇诺啉减轻了蓝蛙素诱导的小鼠化生管的非典型增生和胰腺纤维化
Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.
摘要(中文译文)
慢性胰腺炎（CP）是一种进行性纤维炎症性疾病，其中腺泡-导管化生（ADM）与纤维化形成恶性循环，是胰腺癌发生的早期事件。防己诺林碱是一种来源于粉防己的双苄基异喹啉生物碱，具有抗炎和抗纤维化特性，但其在ADM-纤维化病变中的作用尚不清楚。本研究旨在探讨防己诺林碱对化生导管非典型增生及胰腺纤维化的作用，并阐明其潜在机制。采用网络药理学、生物信息学、分子对接、动力学模拟和细胞实验来阐明并验证其潜在机制。采用C57BL/6 J小鼠模型阐明防己诺林碱的作用及其肝毒性、肾毒性和心脏毒性。防己诺林碱减轻了雨蛙素诱导的化生导管非典型增生（64.3%），并减少了胰腺纤维化（70.8%）。在分子机制方面，它与原癌基因酪氨酸蛋白激酶SRC（SRC）和受体酪氨酸蛋白激酶ERBB-2（ERBB2）的激酶结构域靶向结合，抑制其磷酸化，阻断下游黏着斑激酶（FAK）/锌指E盒结合同源盒1（ZEB1）信号通路，逆转上皮-间质转化（EMT），减弱癌症干性特征，并减少促纤维化因子的分泌。这些作用破坏了ADM与纤维化之间的恶性循环。防己诺林碱是治疗化生导管非典型增生和胰腺纤维化的一种有前景的多靶点治疗候选药物。
Abstract
Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease in which acinar-to-ductal metaplasia (ADM) and fibrosis form a vicious cycle, representing an early event in pancreatic carcinogenesis. Fangchinoline, a bisbenzylisoquinoline alkaloid from Stephania tetrandra, exhibits anti-inflammatory and anti-fibrotic properties, although its role in ADM-fibrotic lesions remains unknown yet. To investigate the effects of fangchinoline on atypical hyperplasia of metaplastic ducts and pancreatic fibrosis, and to clarify its underlying mechanisms. Network pharmacology, bioinformatics, molecular docking, dynamics simulations, and cellular assays were used to elucidate and verify the underlying mechanisms. A C57BL/6 J mouse model was used to elucidate the effects, hepatotoxicity, nephrotoxicity, and cardiotoxicity of fangchinoline. Fangchinoline alleviated caerulein-induced atypical hyperplasia of metaplastic ducts (64.3%) and reduced pancreatic fibrosis (70.8%). In terms of molecular mechanisms, it targeted bound to the kinase domains of proto-oncogene tyrosine-protein kinase SRC (SRC) and receptor tyrosine-protein kinase ERBB-2 (ERBB2), suppressed their phosphorylation, blocked the downstream focal adhesion kinase (FAK)/zinc finger E-box binding homeobox 1 (ZEB1) signalling, reversed epithelial-mesenchymal transition (EMT), attenuated cancer stemness properties, and reduced the secretion of pro-fibrotic factors. These actions disrupted the vicious cycle between ADM and fibrosis. Fangchinoline is a promising multi-target therapeutic candidate for atypical hyperplasia of metaplastic ducts and pancreatic fibrosis.
如何引用
AMA
Xinru Du, Yan Cai, Luyi Zhang, Mengyue Ji, Yuanyuan Sun, Aoming Ye, et al. Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158538.
APA
Xinru Du, Yan Cai, Luyi Zhang, Mengyue Ji, Yuanyuan Sun, Aoming Ye, et al (2026). Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158538
GB/T 7714
Xinru Du, Yan Cai, Luyi Zhang, Mengyue Ji, Yuanyuan Sun, Aoming Ye, et al. Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158538.
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