Multi-omics revealed the mechanisms of Codonopsis pilosula aqueous extract in improving UC through blocking abnormal activation of PI3K/Akt signaling pathway

Codonopsis pilosula (DS), a traditional Chinese medicine, had been used to regulate the immune, digestive and circulatory systems of the human, as well as protect the gastrointestinal tract, improve lung function.The aim of study was to explore the effects and mechanism of Codonopsis pilosula aqueous extract (DS) intervention in improving ulcerative colitis (UC).UC model rats were established using combination of TNBS and ethanol. Tissue samples were collected for transcriptome and metabolomics analysis. Network pharmacology was performed on DS to identify bioactive compounds. Western blot was used to detect the key proteins involved in UC pathogenesis and PI3K/AKT pathways.DS exerted the preventive and therapeutic effects in improving UC via inhibiting abnormal inflammatory responses and promoting antioxidant capacity. Levels of intestinal barrier, oxidative stress and inflammatory mediators were improved to nearly normal level in vivo by DS. Metabolome profiles showed that DS could restore the metabolic disorders associated with the UC pathogenesis. Further transcriptome results showed that DS mainly alleviate UC through inhibiting PI3K/Akt signaling pathway, and various related genes that dramatically expressed in UC Model rats were downregulated by DS. Typically, network pharmacology analysis identified that Glycitein was the hub compounds that involved in the mechanism of DS in improving UC.The results show that Codonopsis pilosula (DS) was an potential excellent material in treating of UC depending on its suitable concentration. Possible therapeutic mechanisms of the DS involved in mitigating colonal inflammation, restoring metabolic disorders, promoting antioxidant capacity, and especially blocking the activation of PI3K/Akt pathway.