OBJECTIVE To explore the possible mechanism of Qingchang Huashi Formula in the treatment of ulcerative colitis (UC).

METHODS Fifty C57BL/6 male mice were randomly divided into a control (Ctrl) group, a model group, a low-dose Qingchang Huashi Formula group, a high-dose Qingchang Huashi Formula group, and a 5-aminosalicylic acid (5-ASA) group based on body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium (DSS) for 6 d. On d7 and d8, DSS was withdrawn and ultrapure water was given daily. Ultrapure water or different drugs were administered orally throughout the experiment: Ctrl and model groups received 0.2 mL of ultrapure water, while the low-dose and high-dose Qingchang Huashi Formula groups received 6 and 12 g · kg^-1, respectively, and the concentration of 5-ASA was 100 mg · kg^-1. Body weight and fecal characteristics of the mice were recorded daily, and the experiment ended on d9. Serum was collected from mice for serum metabolomics and inflammatory factor expression analysis. The colons of the mice were isolated and their lengths were measured, and the distal colon was obtained for pathological analysis. The livers and colons of the mice were isolated for subsequent total bile acid analysis.

RESULTS Compared with the Ctrl group, the model group mice showed a significant decrease in body weight and colon length (P < 0.000 1), a remarkable increase in disease activity index (P < 0.000 1). The concentration of inflammatory factors IL-1β and TNF-α was significantly increased (P < 0.000 1). High-dose and low-dose Qingchang Huashi Formula, as well as 5-ASA could significantly alleviate the loss of body weight, increased DAI, colon shortening, and disappearance of colon tissue morphology in mice. Through ELISA testing, it was found the concentration of IL-1β and TNF-α was remarkably decreased after Qingchang Huashi Formula and 5-ASA treatment (P < 0.01, P < 0.000 1). Through LC-MS analysis of serum metabolites and KEGG enrichment analysis, we found that intervention with Qingchang Huashi Formula could significantly affect the primary bile acid synthesis, secondary bile acid synthesis and bile secretion. Using total bile acid reagent kit, we found that the total bile acid in the liver of colitis mice did not show significant changes when compared with the Ctrl group of mice, and the concentration of total bile acid in the serum was significantly reduced, the concentration of TBA in the colon was significantly increased (P < 0.05). After intervention with the Qingchang Huashi Formula, the concentration of total bile acid in the serum of mice was significantly increased, while the concentration of total bile acid in the colon was reduced (P < 0.05). Compared with mice in Ctrl group, the levels of deoxycholic acid (DCA) and taurine deoxycholic acid (TDCA) in serum of colitis mice were significantly reduced (P < 0.05). After intervention with Qingchang Huashi Formula, the levels of DCA, TDCA and Ursodeoxycholic acid (UDCA) in serum of mice were restored (P < 0.01).

CONCLUSION Qingchang Huashi Formula can effectively relieve DSS-induced colitis in mice, reducing immune inflammatory response, reregulating the disorder of serum metabolism and enterohepatic circulation.