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A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion
Published on: February 28, 2021
Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis
Pengyuan Wang1,2,3, Bangwei Huang1,3, Yu Liu1,3,4,5
1Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
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.
Insights
Corynoline, a traditional Chinese medicine compound, effectively reduces pancreatic fibrosis by inhibiting collagen synthesis and the NF-κB pathway. This discovery offers a promising new treatment for chronic pancreatitis.
Area of Science:
- Pharmacology
- Gastroenterology
- Traditional Chinese Medicine
Background:
- Pancreatic fibrosis is a key characteristic of chronic pancreatitis.
- Current treatments for chronic pancreatitis lack effective antifibrotic agents.
Purpose of the Study:
- To screen traditional Chinese medicine monomers for antifibrotic properties.
- To investigate the efficacy and mechanism of corynoline in treating pancreatic fibrosis.
Main Methods:
- Screening of 80 traditional Chinese medicine monomers.
- In vitro studies on pancreatic stellate cells (PSCs) and in vivo studies in a mouse model of chronic pancreatitis.
- Identification of corynoline's binding protein (PSMA2) using Lip-SMap and DARTS.
Main Results:
- Corynoline demonstrated dose-dependent reduction of collagen I synthesis in TGF-β1-induced PSCs.
- Corynoline alleviated pancreatic fibrosis, including acinar cell atrophy and collagen deposition, in a mouse model.
- Corynoline inhibited the NF-κB signaling pathway and its antifibrotic effect was dependent on PSMA2.
Conclusions:
- Corynoline exhibits significant antifibrotic effects against pancreatic fibrosis.
- Corynoline is a potential therapeutic agent for chronic pancreatitis.
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