title: Oleanolic acid ameliorates dextran sodium sulfate-induced colitis in mice by restoring the balance of Th17/Treg cells and inhibiting NF-κB signaling pathway.
abstract: In a preliminary experiment, it was found that oleanolic acid (OA), which is widely distributed in food and medicinal plants, inhibited interleukin (IL)-6/tumor growth factor beta-induced differentiation of splenic T cells into Th17 cells. Moreover, OA induced the differentiation of splenic T cells into Treg cells. Therefore, we examined the anti-inflammatory effect of OA in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of OA significantly inhibited DSS-induced colon shortening, macroscopic score, and myeloperoxidase activity. Treatment with OA inhibited DSS-induced differentiation to Th17 cells and downregulated the expression of RORγt and IL-17 in the lamina propria of colon and Treg cell differentiation and Foxp3 and IL-10 expression were increased. OA treatment increased the DSS-suppressed expression of tight junction proteins such as ZO-1, occludin, and claudin-1 in the colon. Moreover, OA treatment inhibited DSS-induced expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17, the activation of NF-κB and mitogen-activated protein kinases, and increased IL-10 expression. OA also inhibited the activation of NF-κB and expression of proinflammatory cytokines in LPS-stimulated peritoneal macrophages. These findings suggest that OA may ameliorate inflammatory diseases such as colitis by inhibiting Th17 cell differentiation and increasing Treg cell differentiation.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Geum-Dan
authors.initials: GD
authors.lastname: Kang
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Sumin
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: dhkim@khu.ac.kr.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D009828:Oleanolic Acid / Q000627:therapeutic use*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D009828:Oleanolic Acid; D016264:Dextran Sulfate; D009195:Peroxidase
keywords: Colitis; Inflammation; Oleanolic acid; Th17 cell; Treg cell