2. Academic Validation
  3. Biochanin a ameliorates DSS-induced ulcerative colitis by improving colonic barrier function and protects against the development of spontaneous colitis in the Muc2 deficient mice

Biochanin a ameliorates DSS-induced ulcerative colitis by improving colonic barrier function and protects against the development of spontaneous colitis in the Muc2 deficient mice

  • Chem Biol Interact. 2024 Apr 20:395:111014. doi: 10.1016/j.cbi.2024.111014.
Haina Zhang 1,  Xueqi Wang 2,  Linxian Zhao 3,  Kai Zhang 3,  Jiaming Cui 4,  Guangmeng Xu 5
Affiliations

Affiliations

  • 1 Department of Rehabilitation, The Second Hospital of Jilin University, Jilin University, Changchun, 130000, PR China.
  • 2 Department of Cell Biology and Biophysics, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, PR China.
  • 3 Department of General Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, 130000, PR China.
  • 4 Changchun University of Chinese Medicine, Jilin University, Changchun, 130000, PR China.
  • 5 Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, 130000, PR China. Electronic address: [email protected].
PMID: 38648921 DOI: 10.1016/j.cbi.2024.111014
Abstract

There is an increasing appreciation that colonic barrier function is closely related to the development and progression of colitis. The mucus layer is a crucial component of the colonic barrier, responsible for preventing harmful bacteria from invading the intestinal epithelium and causing inflammation. Furthermore, a defective mucus barrier is also a significant characteristic of ulcerative colitis (UC). Biochanin A (BCA), an isoflavonoid, has garnered increasing interest due to its significant biological activities. However, the impact of BCA on UC has not been reported yet. In this study, we used a dextran sodium sulfate (DSS)-induced ulcerative colitis model and the Muc2 deficient (Muc2-/-) mice spontaneous colitis model to explore the mechanisms of BCA in the treatment of UC. Here, we verified that DSS-induced UC was observably attenuated and spontaneous colitis in Muc2-/- mice was relieved by BCA. Treatment with BCA improved colitis-related symptoms and reduced intestinal permeability by upregulating the levels of goblet cells and tight junction (TJ) proteins. In addition, we confirmed that BCA promotes Autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway, thereby alleviating DSS-induced UC. In addition, the administration of BCA was able to reduce Apoptosis and promote proliferation by suppressing Cleaved Caspase-3 (Cleaved Cas-3) expression, and increasing PCNA and Ki67 levels. Further research revealed that BCA treatment ameliorated spontaneous colitis and alleviated epithelial damage in Muc2-/- mice by restoring the intestinal barrier and promoting Autophagy. Our results demonstrated that BCA alleviated UC by enhancing intestinal barrier function and promoting Autophagy. These findings indicate that BCA may be a novel treatment alternative for UC.

Keywords

Autophagy; Biochanin a; Intestinal barrier; Mucus; Ulcerative colitis.

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