Bear bile powder inhibits the release of NLRP3 by activating the cAMP/PKA/CREB signaling pathway to treat dextran sulfate sodium-induced colitis in mice
image: BBPH, bear bile powder high dose; BBPL, bear bile powder low dose; DSS, dextran sulfate sodium; NC, normal control; 5-ASA, 5-Amino salicylic acid.
Credit: Yongshen Ren, Huiling Tian
Background and objectives
Ulcerative colitis (UC) is a chronic autoimmune disease that mainly affects the rectum and colon. The symptoms primarily include abdominal pain, diarrhea, and bloody stools. The incidence of UC continues to increase each year. Bear bile powder (BBP) is a well-known traditional medicine that remains in use due to its outstanding efficacy. This study aimed to elucidate the therapeutic effects and molecular mechanisms of BBP on dextran sulfate sodium (DSS)-induced UC.
Methods
DSS-induced UC model mice were created and then randomly assigned to the following groups: control, DSS-treated, 5-amino salicylic acid-treated, BBP low dose, and BBP high dose. Treatment was administered by gavage. Disease activity index, body weight loss, colon histopathology, colon length, and the expression of inflammatory cytokines were measured. Samples of the intestinal content were collected, and differences in the gut microbiota were analyzed by 16S rDNA sequencing.
Results
The experimental results demonstrated that BBP significantly alleviated the symptoms and histopathological scores in UC mice, reduced the production of interleukin-6, interleukin-1β, tumor necrosis factor-α, malondialdehyde, nitric oxide, and myeloperoxidase, and upregulated the expression of cyclic adenosine monophosphate (cAMP), protein kinase A, and cAMP-response element binding protein. Moreover, 16S rRNA sequencing revealed that the gut microbiota of mice in the DSS-treated group was disordered compared to the control group. The abundance of gut microbiota in the treatment groups improved to varying degrees.
Conclusions
Together, these results indicate that BBP significantly improves the inflammatory symptoms of mice with acute colitis, which may be related to its upregulation of the cAMP/protein kinase A/cAMP-response element binding protein signaling pathway, inhibition of NOD-like receptor thermal protein domain associated protein 3 inflammasome secretion, and regulation of gut microbiota.
Full text:
https://www.xiahepublishing.com/2835-6357/FIM-2024-00009
The study was recently published in the Future Integrative Medicine.
Future Integrative Medicine (FIM) publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.
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