Su-Min Lim1, Geum-Dan Kang1, Jin-Ju Jeong1, Hyun Sik Choi2, Dong-Hyun Kim3. 1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea. 2. DongWha Pharm Research Institute, 35-71, Topsil-ro, Giheung-gu, Yongin-Shi, Gyeonggi, 46-902 South Korea. 3. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea. Electronic address: dhkim@khu.ac.kr.
Abstract
BACKGROUND: Anemarrhena asphodeloides (Liliaceae family) and Mangifera indica L. (Anacardiaceae family) contain neomangiferin as the main active constituent and have been used to treat inflammation, asthma, and pain. PURPOSE: A preliminary study found that neomangiferin inhibited splenic T cell differentiation into Th17 cells and promoted Treg cell production in vitro. Therefore, we examined its anti-colitic effects in vitro and in vivo. METHODS: Splenocytes isolated from C57BL/6J mice were treated with neomangiferin. Colitis was either induced in vivo by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to C57BL/6J mice or occurred spontaneously in colitis caused by interleukin (IL)-10 knockout at age of 13 weeks. Mice were treated daily with neomangiferin or sulfasalazine. Inflammatory markers, cytokines, enzymes and transcription factors were measured by enzyme-linked immunosorbent assay, immunoblot, and flow cytometry. RESULTS: Neomangiferin suppressed retinoic acid receptor-related orphan receptor gamma t (RORγt) and IL-17 expression in IL-6/transforming growth factor β-stimulated Th17 splenocytes and increased IL-10 expression in vitro. Mouse TNBS-induced colon shortening, macroscopic score, and myeloperoxidase activity were inhibited by neomangiferin, which also reduced TNBS-induced activation of nuclear factor-κB and extracellular signal-regulated kinases, as well as expression of inducible nitric oxide synthase and cyclooxygenase-2. In addition, neomangiferin inhibited TNBS-induced expression of tumor necrosis factor-α, IL-17, IL-6, and IL-1β, and increased IL-10 expression. Neomangiferin inhibited TNBS-induced differentiation to Th17 cells and promoted the development of Treg cells. Moreover, in IL-10(-/-) mice, neomangiferin inhibited colonic myeloperoxidase activity, suppressed Th17 cell differentiation, and reduced levels of TNF-α and IL-17. CONCLUSION: Neomangiferin may restore the balance between Th17/Treg cells by suppressing IL-17 and RORγt expression and inducing IL-10 and forkhead box P3 expression, thus ameliorating colitis.
BACKGROUND:Anemarrhena asphodeloides (Liliaceae family) and Mangifera indica L. (Anacardiaceae family) contain neomangiferin as the main active constituent and have been used to treat inflammation, asthma, and pain. PURPOSE: A preliminary study found that neomangiferin inhibited splenic T cell differentiation into Th17 cells and promoted Treg cell production in vitro. Therefore, we examined its anti-colitic effects in vitro and in vivo. METHODS: Splenocytes isolated from C57BL/6J mice were treated with neomangiferin. Colitis was either induced in vivo by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to C57BL/6J mice or occurred spontaneously in colitis caused by interleukin (IL)-10 knockout at age of 13 weeks. Mice were treated daily with neomangiferin or sulfasalazine. Inflammatory markers, cytokines, enzymes and transcription factors were measured by enzyme-linked immunosorbent assay, immunoblot, and flow cytometry. RESULTS:Neomangiferin suppressed retinoic acid receptor-related orphan receptor gamma t (RORγt) and IL-17 expression in IL-6/transforming growth factor β-stimulated Th17 splenocytes and increased IL-10 expression in vitro. MouseTNBS-induced colon shortening, macroscopic score, and myeloperoxidase activity were inhibited by neomangiferin, which also reduced TNBS-induced activation of nuclear factor-κB and extracellular signal-regulated kinases, as well as expression of inducible nitric oxide synthase and cyclooxygenase-2. In addition, neomangiferin inhibited TNBS-induced expression of tumor necrosis factor-α, IL-17, IL-6, and IL-1β, and increased IL-10 expression. Neomangiferin inhibited TNBS-induced differentiation to Th17 cells and promoted the development of Treg cells. Moreover, in IL-10(-/-) mice, neomangiferin inhibited colonic myeloperoxidase activity, suppressed Th17 cell differentiation, and reduced levels of TNF-α and IL-17. CONCLUSION:Neomangiferin may restore the balance between Th17/Treg cells by suppressing IL-17 and RORγt expression and inducing IL-10 and forkhead box P3 expression, thus ameliorating colitis.
Authors: Victoria Klepsch; Alexander R Moschen; Herbert Tilg; Gottfried Baier; Natascha Hermann-Kleiter Journal: Front Immunol Date: 2019-05-14 Impact factor: 7.561
Authors: Hilda Vargas-Robles; Karla Fabiola Castro-Ochoa; Alí Francisco Citalán-Madrid; Michael Schnoor Journal: World J Gastroenterol Date: 2019-08-14 Impact factor: 5.742