Integrating network pharmacology and experimental verification to explore the mucosal protective effect of Chimonanthus nitens Oliv. Leaf Granule on ulcerative colitis

Ethnopharmacological relevance: Chimonanthus nitens Oliv. Leaf Granule (COG) is a commonly used clinical preparation of traditional Chinese medicine for the treatment of cold, but there are folk reports that it can treat diarrhea and other gastrointestinal diseases. Therefore, the mechanism of COG in the treatment of ulcerative colitis with diarrhea as the main symptom needs to be studied.

Aim of the study: Combined network pharmacology and experimental validation to explore the mechanism of COG in the treatment of ulcerative colitis.

Materials and methods: First, the main components of COG were characterized by liquid chromatography-mass spectrometry (LC-MS); subsequently, a network pharmacology approach was used to screen the effective chemical components and action targets of COG to construct a target network of COG for the treatment of ulcerative colitis (UC). The protein-protein interaction network (PPI) and literature reports were combined to identify the potential targets of COG for the treatment of UC. Finally, the predicted results of network pharmacology were validated by animal and cellular experiments.

Results: 19 components of COG were characterized by LC-MS, among which 10 bioactive components could act on 377 potential targets of UC. Key therapeutic targets were collected, including Src, HSP90AA1, PIK3RI, MAPK1 and ESR1. KEGG results are enriched in pathways related to oxidative stress. Molecular docking analysis showed good binding activity of main components and target genes. Animal experiments showed that COG significantly relieved the colitis symptoms in mice, regulated the Treg/Th17 balance, and promoted the secretion of IL-10 and IL-4, along with the inhibition of IL-1β and TNF-α. Additionally, COG reduced the Apoptosis of colon epithelial cells, and significantly improved the levels of SOD, MAO, GSH-px, and inhibited MDA, iNOS, eNOS in colon. Also, it increased the expression of tight junction proteins such as ZO-1, Claudin1, Occludin and E-cadherin. In vitro experiments, COG inhibited the oxidative stress and inflammatory injury of HCT116 cells induced by LPS.

Conclusions: Combining network pharmacology and in vitro and in vivo experiments, COG was verified to have a good protective effect in UC, which may be related to enhancing antioxidation in colon tissues.

Anti-inflammatory; Anti-oxidation; Chimonanthus nitens Oliv. leaf; Network pharmacology; Ulcerative colitis.