Ji-Won Han1, Do-Wan Shim1, Eun-Jeong Shim1, Myong-Ki Kim2, Yong-Kook Shin3, Su-Bin Kwak1, Sushruta Koppula1, Tack-Joong Kim4, Tae-Bong Kang1, Kwang-Ho Lee5. 1. Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea. 2. Department of Food Science and Engineering, Seowon University, Cheongju, South Korea. 3. Department of Natural Medicine Resources, Semyung University, Jecheon, South Korea. 4. Division of Biological Science and Technology, Institute of Biomaterials, Yonsei University, Wonju, South Korea. 5. Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea. Electronic address: kwangho@kku.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsis mouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy. RESULTS: SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsis mouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation. CONCLUSION: This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.
ETHNOPHARMACOLOGICAL RELEVANCE: Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models. MATERIALS AND METHODS:Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsismouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy. RESULTS:SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsismouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation. CONCLUSION: This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.