2. Academic Validation
  3. Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis

Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis

  • Phytomedicine. 2022 Jan 29;98:153961. doi: 10.1016/j.phymed.2022.153961.
Wei Yu 1,  Guoliang Wang 1,  Chang Lu 1,  Chen Liu 1,  Lu Jiang 1,  Zizheng Jiang 1,  Zhenghao Liang 1,  Xiao Wang 1,  Zheng Qin 2,  Jing Yan 3
Affiliations

Affiliations

  • 1 Department of Physiology, Jining Medical University, Jining, Shandong, China.
  • 2 Shandong University, Jinan, Shandong, China.
  • 3 Department of Physiology, Jining Medical University, Jining, Shandong, China. Electronic address: [email protected].
PMID: 35121392 DOI: 10.1016/j.phymed.2022.153961
Abstract

Background: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by an overactive immune response and destruction of the colorectal epithelium with intricate pathological factors. Shenlingbaizhu (SLBZ) formula, included in the Chinese Pharmacopoeia 2020, has been widely utilized to treat UC.

Purpose: The present study was designed to uncover the underlying molecular mechanisms of SLBZ formula against UC.

Methods: A murine model of experimental colitis was established by orally feeding 2% dextran sodium sulfate (DSS) to mice for 7 days, followed by SLBA treatment for the next 15 days. Network pharmacology analysis was performed to predict the pharmacological mechanisms. High-throughput 16S rRNA sequencing integrated with liquid chromatography-mass spectrometry (LC-MS) was conducted on mouse stool in order to determine alterations in the composition of the intestinal microbiota and metabolites. Western blotting, immunofluorescence, and flow cytometry were performed to examine the anti-inflammatory role of SLBZ.

Results: DSS treatment induced experimental colitis, and this induction was alleviated by SLBZ treatment, as evidenced by rescued pathological symptoms in the experimental colitis mouse groups. Network pharmacology analysis showed that SLBZ-target genes were enriched in pathogen-induced infectious and inflammatory pathways, as well as neoplastic processes. SLBZ administration also modulated the gut microbiota composition and metabolic profiles of experimental colitis mice and alleviated the progression of experimental colitis. We further showed via in-vitro experiments that SLBZ suppressed macrophage (Mφ) transition to pro-inflammatory phenotype (M1), rescued tumor necrosis factor-α (TNFα)-induced Pyroptosis of intestinal organoids (IOs), and decreased the recruitment of Mφs by epithelial cells.

Conclusion: SLBZ formula is an effective treatment for murine colitis and showed a stronger therapeutic capacity than melasazine. The pharmacological mechanisms of SLBZ involve the re-establishment of an anti-inflammatory milieu and healthy microbiome, which favors mucosal healing.

Keywords

Inflammatory bowel disease; Intestinal organoids; Macrophages; Shenlingbaizhu formula; Ulcerative colitis.

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