Wang JJ, Fan YH, Cao WT, Huang R, Yao XY, Li ML. Mechanism of Wuling powder modulating proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of ulcerative colitis complicated with depression. World J Gastroenterol 2025; 31(8): 100227 [DOI: 10.3748/wjg.v31.i8.100227]
Corresponding Author of This Article
Yi-Hong Fan, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Shangcheng District, Hangzhou 310003, Zhejiang Province, China. yhfansjr@163.com
Research Domain of This Article
Behavioral Sciences
Article-Type of This Article
Basic Study
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/
World J Gastroenterol. Feb 28, 2025; 31(8): 100227 Published online Feb 28, 2025. doi: 10.3748/wjg.v31.i8.100227
Mechanism of Wuling powder modulating proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of ulcerative colitis complicated with depression
Jing-Jing Wang, Yi-Hong Fan, Wan-Ting Cao, Rong Huang, Xin-Yi Yao, Meng-Lin Li
Jing-Jing Wang, Yi-Hong Fan, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang Province, China
Wan-Ting Cao, Department of Gastroenterology, Beilun District Hospital of Traditional Chinese Medicine, Ningbo 315800, Zhejiang Province, China
Rong Huang, Department of Gastroenterology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing 314000, Zhejiang Province, China
Xin-Yi Yao, Department of Gastroenterology, Deqing County People’s Hospital, Huzhou 313200, Zhejiang Province, China
Meng-Lin Li, Department of Gastroenterology, Jinhua Fifth Hospital, Jinhua 321000, Zhejiang Province, China
Author contributions: Wang JJ and Cao WT performed the experiments, analyzed the data and wrote the paper; Fan YH designed the research, revised the paper and contributed equally to this study; Huang R and Yao XY performed parts of the experiments and provided valuable suggestions for this study; Li ML contributed new analytic tools. All authors have read and approved the final manuscript.
Supported by Zhejiang Provincial Administration of Traditional Chinese Medicine, No. 2021ZA057.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University (IACUC protocol number: Protocol No. 20200914-10).
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: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Hong Fan, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Shangcheng District, Hangzhou 310003, Zhejiang Province, China. yhfansjr@163.com
Received: August 10, 2024 Revised: November 22, 2024 Accepted: January 8, 2025 Published online: February 28, 2025 Processing time: 165 Days and 21.8 Hours
Abstract
BACKGROUND
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. The most common psychological issue in UC patients is varying degrees of depression, which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition. UC drugs combined with antianxiety and antidepression drugs can alleviate symptoms of both depression and UC. Brain-derived neurotrophic factor (BDNF) precursor (proBDNF)/p75 neurotrophin receptor (p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B (TrkB) signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.
AIM
To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depression.
METHODS
Depression was established in C57BL/6J mice via chronic restraint stress, and the UC model was induced with dextran sodium sulfate (DSS). In the treatment stage, mesalazine (MS) was the basic treatment, Wuling powder was the experimental treatment, and fluoxetine was the positive control drug for treating depression. Changes in intestinal mucosal inflammation, behaviour, and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.
RESULTS
In the depression groups, Wuling powder decreased the immobility time, increased the distance travelled in the central zone and the total distance travelled, and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways. In the DSS and chronic restraint stress + DSS groups, immobility time increased, distance travelled in the central zone and total distance travelled decreased, activity of the proBDNF/p75NTR/sortilin pathway was upregulated, and activity of the BDNF/TrkB pathway was downregulated, indicating that mice with UC often have comorbid depression. Compared with those of MS alone, Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.
CONCLUSION
This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.
Core Tip: A common psychological problem in patients with ulcerative colitis is varying degrees of depression, which can cause the patient’s condition to worsen. Wuling powder is widely used to treat anxiety, depression, insomnia and headache. Previous studies have found that the balance between brain-derived neurotrophic factor (BDNF) precursor/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signalling is essential for maintaining brain homeostasis and preventing the development of depressive behaviours. Our study suggests that Wuling powder may play an antidepressant role by regulating the balance of the BDNF precursor/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signalling pathways. Moreover, Wuling powder combined with mesalazine can further relieve intestinal inflammation in mice with ulcerative colitis and depression.
