Serum and colon metabolomics study reveals the anti-ulcerative colitis effect of Croton crassifolius Geisel

Croton crassifolius Geisel (CCG, also known as Ji-Gu-Xiang in Traditional Chinese Medicine), is traditionally prescribed for the therapy of rheumatic arthritis and gastrointestinal ulcer. However, the effect of CCG on ulcerative colitis (UC) has not been investigated.

To explore the therapeutic potential and underlying mechanism of CCG extract against UC by colonic and serum metabolomics.

In order to standardize the CCG extract, UPLC-QTOF-MS was used for quantitative and qualitative analysis of the representative terpenoids. C57BL/6J mice were divided into control, Dextran Sulfate Sodium (DSS), mesalazine (100 mg•kg^-1), CCG extract (150 and 600 mg•kg^-1) groups. The mice were provided 3% DSS dissolved in distilled water ad libitum for 7 days except control group. Weight change, disease activity index (DAI), colon lengths and expression of inflammatory mediators iNOS and COX-2 in colonic tissue were determined. Serum and colon metabolomics using UPLC-QTOF-MS technology coupled with multivariate data analysis were performed to reveal the underlying mechanism.

Thirty-five terpenoids in CCG were identified by fingerprint, in which ten representative terpenes were quantified. CCG could relieve the weight loss, the degree of bloody stool and ulcer of colon, as well as significantly lowering the expression level of iNOS and COX-2. Metabolomics analysis showed that 25 biomarkers were obviously interfered by CCG treatment and 16 of them were highly correlated with the efficacy of CCG. The analysis of metabolic pathway showed that the anti-UC effect of CCG was associated with the regulation on linoleic acid metabolism, sphingolipid metabolism, α-linolenic acid metabolism, and glycerophospholipids metabolism.

The oral administration of CCG significantly alleviated DSS-induced UC symptoms by reducing inflammation and rectifying the metabolic disorder. CCG may provide a new strategy for the management of UC.