Ji-Sun Shin1, Eu-Jin Cho2, Hye-Eun Choi3, Ji-Hyung Seo2, Hyo-Jin An4, Hee-Juhn Park5, Young-Wuk Cho6, Kyung-Tae Lee7. 1. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea. 2. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. 3. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. 4. Department of Pharmacology, College of Oriental Medicine, Sangji University, Gangwon-do, Republic of Korea. 5. Department of Botanical Resources, Sangji University, Gangwon-do, Republic of Korea. 6. Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea. 7. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. Electronic address: ktlee@khu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: Experimental colitis was induced by DSS for 7 days in ICR mice. Disease activity indices (DAI) took into account body weight, stool consistency, and gross bleeding. Histological changes and macrophage accumulation were observed by immunohistochemical analysis. Pro-inflammatory markers were determined using immunoassays, RT-PCR, and real time PCR. Signaling pathway involving nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation was determined by luciferase assay and Western blotting. RESULTS: In DSS-induced colitis mice, TFRC improved DAIs and pathological characteristics including colon shortening and colonic epithelium injury. TFRC suppressed tissue levels of pro-inflammatory cytokines and reduced macrophage infiltration into colonic tissues. In LPS-induced RAW 264.7 macrophages, TFRC inhibited the production of NO, PGE2, and pro-inflammatory cytokines by down-regulating the activation of NF-κB and p38 MAPK signaling. CONCLUSION: The study demonstrates that TFRC has potent anti-inflammatory effects on DSS-induced colonic injury and LPS-induced macrophage activation, and supports its possible therapeutic and preventive roles in colitis.
ETHNOPHARMACOLOGICAL RELEVANCE: Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: Experimental colitis was induced by DSS for 7 days in ICR mice. Disease activity indices (DAI) took into account body weight, stool consistency, and gross bleeding. Histological changes and macrophage accumulation were observed by immunohistochemical analysis. Pro-inflammatory markers were determined using immunoassays, RT-PCR, and real time PCR. Signaling pathway involving nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation was determined by luciferase assay and Western blotting. RESULTS: In DSS-induced colitismice, TFRC improved DAIs and pathological characteristics including colon shortening and colonic epithelium injury. TFRC suppressed tissue levels of pro-inflammatory cytokines and reduced macrophage infiltration into colonic tissues. In LPS-induced RAW 264.7 macrophages, TFRC inhibited the production of NO, PGE2, and pro-inflammatory cytokines by down-regulating the activation of NF-κB and p38 MAPK signaling. CONCLUSION: The study demonstrates that TFRC has potent anti-inflammatory effects on DSS-induced colonic injury and LPS-induced macrophage activation, and supports its possible therapeutic and preventive roles in colitis.
Authors: Congqiao Jiang; Pingsheng Zhu; Yi Shi; Wujun Xiang; Sitang Ge; Zongbing Zhang; Lugen Zuo Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-07-30
Authors: Daniel Mirosław Grochowski; Roman Paduch; Adrian Wiater; Adrianna Dudek; Małgorzata Pleszczyńska; Monika Tomczykowa; Sebastian Granica; Paulina Polak; Michał Tomczyk Journal: Evid Based Complement Alternat Med Date: 2016-12-22 Impact factor: 2.629