Network pharmacology-based identification of the protective mechanisms of taraxasterol in experimental colitis

Taraxasterol, a pentacyclic-triterpene, has been reported to exert potent anti-inflammatory activity. However, the molecular mechanisms by which taraxasterol attenuates acute experimental colitis (AEC) remain undocumented.

A network pharmacology approach was used to identify the candidate and collective targets of taraxasterol and acute colitis, and an AEC model was established by oral administration of dextran sulfate sodium (DSS) in mice. Body weight and colon lengths were then examined, the pathological scoring was assessed by using hematoxylin and eosin staining, and the expression levels of target genes were further confirmed by qRT-PCR and immunohistochemistry (IHC) analysis in taraxasterol treated AEC models.

14 collective targets of taraxasterol and acute colitis were identified by a network pharmacology analysis, including PPARG, JAK2, MMP3, NR1I2 and PTPN11. Further investigations in an AEC model showed that, taraxasterol alleviated the unfavorable clinical symptoms and attenuated the intestinal inflammation response by reducing the cytokines TNF-α, IL-1β and IL-6 levels. qRT-PCR and IHC analysis evidenced that, taraxasterol decreased MMP3 expression levels, but increased PPARG expression levels in AEC models as compared with the DSS group.

Our findings demonstrated that taraxasterol improved DSS-induced AEC through regulating MMP3 and PPARG expression, providing a new insight into the potential therapeutic strategies for acute colitis.