2. Academic Validation
  3. Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis

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

  • J Gastroenterol. 2024 Aug 15. doi: 10.1007/s00535-024-02145-4.
Pengyuan Wang # 1 2 3,  Bangwei Huang # 1 3,  Yu Liu # 1 3 4 5,  Xin Tan # 1 3,  Libo Liu 2,  Baoru Zhang 2,  Zhaoshen Li 1 3,  Le Kang 6 7,  Lianghao Hu 8 9
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • 2 Department of Gastroenterology, The 981st Hospital of PLA, Chengde, 067000, Hebei, China.
  • 3 Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China.
  • 4 Department of Gastroenterology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210000, Jiangsu, China.
  • 5 Department of Pharmacology, College of Pharmacy, Naval Medical University, Shanghai, 200433, China.
  • 6 Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. Kangle_medicine@hotmail.com.
  • 7 Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China. Kangle_medicine@hotmail.com.
  • 8 Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. lianghao-hu@smmu.edu.cn.
  • 9 Shanghai Institute of Pancreatic Diseases, Shanghai, 200433, China. lianghao-hu@smmu.edu.cn.
  • # Contributed equally.
PMID: 39145797 DOI: 10.1007/s00535-024-02145-4
Abstract

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.

Keywords

Chronic pancreatitis; Corynoline; PSCs; PSMA2; Pancreatic fibrosis.

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