Mechanism of Wuling powder modulating proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of ulcerative colitis complicated with depression.

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 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.