Li KL, Zhao Y, Shang WJ, Guo QH, Liu HT, Zhang JY, Jia XL, Liu BR. OH-CATH30 targets CD40 to suppress NF-κB signaling and promote arachidonic acid metabolic reprogramming in acute pancreatitis. World J Gastroenterol 2026; 32(36): 121753 [DOI: 10.3748/wjg.121753]
Corresponding Author of This Article
Bing-Rong Liu, MD, PhD, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccliubr@zzu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
research-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Li KL, Zhao Y, Shang WJ, Guo QH, Liu HT, Zhang JY, Jia XL, Liu BR. OH-CATH30 targets CD40 to suppress NF-κB signaling and promote arachidonic acid metabolic reprogramming in acute pancreatitis. World J Gastroenterol 2026; 32(36): 121753 [DOI: 10.3748/wjg.121753]
Ke-Liang Li, Yue Zhao, Qi-Hang Guo, Ji-Yu Zhang, Bing-Rong Liu, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Wei-Jie Shang, Department of Human Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan Province, China
Hai-Tao Liu, Henan Institute for Drug and Medical Device Inspection, Zhengzhou 450008, Henan Province, China
Xue-Lin Jia, Education Office, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Li KL, Zhao Y, Shang WJ, Jia XL, and Liu BR designed the research study; Li KL, Guo QH, Liu HT, and Zhang JY performed the research; Li KL, Shang WJ, and Guo QH analyzed the data; Li KL wrote the manuscript; Liu BR revised the manuscript; Jia XL and Liu BR supervised the study. All authors have read and approved the final manuscript.
Supported by Zhongyuan Talent Program, No. ZYYCYU202012113; Key R&D Program of Henan Province, No. 231111311600; and Outstanding Foreign Scientist Studio Project of Henan Province, No. GZS2020006.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Experimental Animal Center of Zhengzhou University, No. ZZU-LAC20240531.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data underlying this article are available from the corresponding author on reasonable request.
Corresponding author: Bing-Rong Liu, MD, PhD, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccliubr@zzu.edu.cn
Received: April 1, 2026 Revised: April 25, 2026 Accepted: May 29, 2026 Published online: September 28, 2026 Processing time: 143 Days and 5.4 Hours
Abstract
BACKGROUND
Acute pancreatitis (AP) currently lacks targeted therapeutic interventions. The antimicrobial peptide OH-CATH30 is derived from Ophiophagus hannah venom and has exhibited potential anti-inflammatory effects; however, its precise mechanism of action in AP remains unclear. We hypothesized that OH-CATH30 targets CD40 to modulate inflammatory signaling and metabolic pathways in AP.
AIM
To investigate the therapeutic mechanisms of OH-CATH30 in AP and its role in targeting CD40.
METHODS
In vitro and in vivo AP models were established. Multi-omics analyses, molecular docking, co-immunoprecipitation, and functional validation were performed. Cell viability, apoptosis, cytokine levels, histopathology, and serum enzyme levels were assessed.
RESULTS
In vitro, OH-CATH30 enhanced cell viability, reduced apoptosis, and inhibited pro-inflammatory cytokine production. In vivo, it improved pancreatic histopathology and reduced serum amylase and lipase levels. Multi-omics integration identified CD40 as a pivotal node that links nuclear factor-kappa B signaling with arachidonic acid metabolism. Molecular docking predicted a binding energy of -8.7 kcal/mol between OH-CATH30 and CD40, which was confirmed by co-immunoprecipitation. Its underlying mechanism was elucidated. Thus, OH-CATH30 inhibits the CD40-tumor necrosis factor receptor-associated factor 6-transforming growth factor beta-activated kinase 1-nuclear factor-kappa B pathway, promotes M1-to-M2 macrophage phenotypic shift, and reduces cyclooxygenase-2/5-lipoxygenase expression. CD40 overexpression negated these protective effects, whereas CD40 knockdown mimicked them.
CONCLUSION
OH-CATH30 mitigates AP by targeting CD40 and orchestrating both inflammatory and metabolic reprogramming. Thus, it is a promising therapeutic candidate. Further validation is warranted in severe disease models and clinical settings.
Core Tip: This study identifies CD40 as a pivotal therapeutic target in acute pancreatitis. The antimicrobial peptide OH-CATH30 binds to CD40 and suppresses the CD40-tumor necrosis factor receptor-associated factor 6-transforming growth factor beta-activated kinase 1-nuclear factor-kappa B signaling cascade. This inhibition drives macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype and corrects arachidonic acid metabolic dysregulation. These findings establish CD40 as a central node that links inflammatory signaling and metabolic reprogramming in acute pancreatitis. Thus, OH-CATH30 is a promising multi-functional therapeutic candidate for this devastating inflammatory disease.
