Kim, Su-yeon Chung, Kyung-Sook Jang, Seo-Yun Han, Hee-Soo Heo, So-Won Lee, Jong Kil Kim, Hyoung Ja Shin, Yu-Kyong Ahn, Hye Shin Lee, Sun Hee Lee, Kyung-Tae 2024-01-19T09:02:49Z 2024-01-19T09:02:49Z 2023-07-27 2023-08 2042-650X https://pubs.kist.re.kr/handle/201004/113442 Ulcerative colitis (UC) is a chronic disease of the colon characterized by mucosal damage and relapsing gastrointestinal inflammation. Hydrangea serrata (Thunb.) Ser. and its bioactive compound, hydrangenol, are reported to have anti-inflammatory effects, but few studies have investigated the effects of hydrangenol in colitis. In the present study, we evaluated for the first time the anti-colitic effects and molecular mechanisms of hydrangenol in a dextran sodium sulfate (DSS)-induced mouse colitis model. To investigate the anti-colitic effects of hydrangenol, DSS-induced colitis mice, HT-29 colonic epithelial cells treated with supernatant from LPS-inflamed THP-1 macrophages, and LPS-induced RAW264.7 macrophages were used. In addition, to clarify the molecular mechanisms of this study, quantitative real time-PCR, western blot analysis, TUNEL assay, and annexin V-FITC/PI double staining analysis were conducted. Oral administration of hydrangenol (15 or 30 mg kg(-1)) significantly alleviated DSS-induced colitis by preventing DAI scores, shortening colon length, and colonic structural damage. F4/80(+) macrophage numbers in mesenteric lymph nodes and macrophage infiltration in colonic tissues were significantly suppressed following hydrangenol treatment in DSS-exposed mice. Hydrangenol significantly attenuated DSS-induced destruction of the colonic epithelial cell layer through regulation of pro-caspase-3, occludin, and claudin-1 protein expression. Moreover, hydrangenol ameliorated abnormal tight junction protein expression and apoptosis in HT-29 colonic epithelial cells treated with supernatant from LPS-inflamed THP-1 macrophages. Hydrangenol suppressed the expression of pro-inflammatory mediators, such as iNOS, COX-2, TNF-& alpha;, IL-6, and IL-1 & beta; through NF-& kappa;B, AP-1, and STAT1/3 inactivation in DSS-induced colon tissue and LPS-induced RAW264.7 macrophages. Taken together, our findings suggest that hydrangenol recovers the tight junction proteins and down-regulates the expression of the pro-inflammatory mediators by interfering with the macrophage infiltration in DSS-induced colitis. Our study provides compelling evidence that hydrangenol may be a candidate for inflammatory bowel disease therapy. English Royal Society of Chemistry Hydrangenol, an active constituent of Hydrangea serrata (Thunb.) Ser., ameliorates colitis through suppression of macrophage-mediated inflammation in dextran sulfate sodium-treated mice Article 10.1039/d3fo01243c 1 Food & Function, v.14, no.15, pp.6957 - 6968 Food & Function 14 15 6957 6968 N scie scopus 001024941500001 Biochemistry & Molecular Biology Food Science & Technology Biochemistry & Molecular Biology Food Science & Technology Article NF-KAPPA-B ULCERATIVE-COLITIS BOWEL-DISEASE WATER EXTRACT EXPRESSION PATHWAY LEAVES CONTRIBUTES ACTIVATION CYTOKINES