Aim of the StudyTo observe the efficacy and safety of CQE in rapidly alleviating inflammatory activity in UC.Materials and MethodsCQE extracts were analyzed by UHPLC–Q Exactive Orbitrap–HRMS. This study used a self-controlled design before and after treatment. A total of 114 UC patients were included and treated with traditional rectal enema administration of CQE. Among them, 107 patients completed the treatment, and 101 patients with complete clinical and laboratory data were included in the final analysis. The primary clinical intestinal symptoms, mucosal endoscopic and pathological changes, laboratory indicators, quality of life scores, and adverse reactions were compared before and after 14 days of enema treatment. A historical comparison was made with previous studies. The expression of intestinal tight junction proteins in the colons of UC patients during active periods was detected using Quantitative Real-time PCR (RT-qPCR) and Western blot (WB).ResultsThe main compounds in CQE were identified, including Gallic acid, Matrine, Oxysophocarpine, Ellagic acid, Prim-O-glucosylcimifugin, Cytisinicline, Danshensu, Protocatechuic acid, Cimifugin, Salvianolic acid A Cytisinicline, Indigo, Indirubin, Tryptanthrin and others. The primary endpoint, defined as the change in modified Mayo score, showed a significant improvement after 14 days of CQE treatment (P < 0.001). The clinical response rate was 94.06% (95/101), and the clinical remission rate was 66.34% (67/101). The endoscopic mucosal healing rate was 76.24% (77/101), and the histological remission rate was 38.61% (39/101). Compared to before treatment, post-treatment scores for clinical intestinal symptoms, Mayo endoscopic scores (MES), Geboes index, fecal calprotectin (FC), and fecal occult blood test (OB) were significantly reduced (P < 0.001). The UCEIS score for the distal rectum and sigmoid colon showed more improvement than the proximal colon (P < 0.01). Hemoglobin (HGB), albumin (ALB), and quality of life scores increased (P < 0.05), while liver and kidney function indicators showed no abnormal elevations after treatment (P < 0.05). Compared to historical data from previous studies using steroids and biologics, CQE significantly improved clinical and endoscopic remission rates. RT-qPCR and WB results demonstrated that the herbal enema helps repair the intestinal mucosal barrier in UC patients.ConclusionCQE can rapidly alleviate inflammatory activity in UC within 14 days and improve patients’ quality of life, with a low incidence of adverse events.