Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Fangchinoline alleviates atypical hyperplasia of metaplastic ducts and pancreatic fibrosis in caerulein-induced mice.
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Du Xinru, Cai Yan, Zhang Luyi, Ji Mengyue, Sun Yuanyuan, Ye Aoming, Zhang Hongquan, Mo Qinliang, Wang Zhendong, Wang Moyan, Li Yalin, Li Taiyu, Tang Chengwu, Ma Jialin, Li Yuan
Аннотация
BACKGROUND: 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.
OBJECTIVE: To investigate the effects of fangchinoline on atypical hyperplasia of metaplastic ducts and pancreatic fibrosis, and to clarify its underlying mechanisms.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Fangchinoline is a promising multi-target therapeutic candidate for atypical hyperplasia of metaplastic ducts and pancreatic fibrosis.
OBJECTIVE: To investigate the effects of fangchinoline on atypical hyperplasia of metaplastic ducts and pancreatic fibrosis, and to clarify its underlying mechanisms.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Fangchinoline is a promising multi-target therapeutic candidate for atypical hyperplasia of metaplastic ducts and pancreatic fibrosis.