title: Ocotillol, a Majonoside R2 Metabolite, Ameliorates 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Restoring the Balance of Th17/Treg Cells.
abstract: In a preliminary experiment, majonoside R2 (MR2), isolated from Vietnamese ginseng (Panax vietnamensis Ha et Grushv.), inhibited differentiation to Th17 cells and was metabolized to ocotillol via pseudoginsenoside RT4 (PRT4) by gut microbiota. Therefore, we examined the inhibitory effects of MR2 and its metabolites PRT4 and ocotillol against Th17 cell differentiation. These ginsenosides significantly suppressed interleukin (IL)-6/tumor growth factor beta-induced differentiation of splenic CD4(+) T cells into Th17 cells and expression of IL-17 in vitro. Among these ginsenosides, ocotillol showed the highest inhibitory effect. We also examined the anti-inflammatory effect of ocotillol in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Oral administration of ocotillol significantly suppressed TNBS-induced colon shortening, macroscopic score, myeloperoxidase activity, and production of nitric oxide and prostaglandin E2. Ocotillol treatment increased TNBS-suppressed expression of tight junction proteins ZO-1, occludin, and claudin-1 in the colon. Treatment with ocotillol inhibited TNBS-induced expression of tumor necrosis factor (TNF)-α and IL-1β, as well as activation of NF-κB and MAPKs. Moreover, treatment with ocotillol inhibited TNBS- induced differentiation to Th17 cells in the lamina propria of colon, as well as expression of T-bet, RORγt, IL-17, and IL-23. Ocotillol treatment also increased Treg cell differentiation and Foxp3 and IL-10 expression. These findings suggest that orally administered MR2 may be metabolized to ocotillol in the intestine by gut microbiota and the transformed ocotillol may ameliorate inflammatory diseases such as colitis by restoring the balance of Th17/Treg cells.
authors.affiliation: †Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Korea.
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: †Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Korea.
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Jeong
authors.affiliation: ‡School of Pharmacy, University of Medicine and Pharmacy, 41 Dinh Tien Hoang Street, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Thi Hong Van
authors.initials: TH
authors.lastname: Le
authors.affiliation: †Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Korea.
authors.forename: Su-Hyeon
authors.initials: SH
authors.lastname: Eun
authors.affiliation: ‡School of Pharmacy, University of Medicine and Pharmacy, 41 Dinh Tien Hoang Street, District 1, Ho Chi Minh City, Vietnam.
authors.forename: Minh Duc
authors.initials: MD
authors.lastname: Nguyen
authors.affiliation: §College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, 151-742, Seoul, Korea.
authors.forename: Jeong Hill
authors.initials: JH
authors.lastname: Park
authors.affiliation: †Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D036145:Ginsenosides / Q000008:administration & dosage*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D051379:Mice; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D036145:Ginsenosides; D020381:Interleukin-17; D053583:Interleukin-1beta; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C000608355:pseudoginsenoside RT4; C098043:majonoside R2; D014302:Trinitrobenzenesulfonic Acid
keywords: Th17 cell; colitis; inflammation; majonoside R2; ocotillol