title: Anti-inflammatory effects of vina-ginsenoside R2 and majonoside R2 isolated from Panax vietnamensis and their metabolites in lipopolysaccharide-stimulated macrophages.
abstract: Panax vietnamensis Ha et Grushv., with its main constituents vina-ginsenoside R2 (VR2) and majonoside R2 (MR2), is used in traditional folk medicine in the hill tribes of Vietnam for anti-fatigue, anti-inflammatory, and life-saving purposes. In a preliminary study, VR2 and MR2 were shown to be metabolized to pseudoginsenoside RT4 (PRT4) and ocotillol by human gut microbiota. Therefore, we measured the anti-inflammatory effects of VR2, MR2, and their metabolites in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Among these ginsenosides, only VR2 exhibited cytotoxicity against peritoneal macrophages. MR2, PRT4, and ocotillol inhibited LPS-stimulated transcription factor (NF)-κB activation, and expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL)-1. However, these ginsenosides did not inhibit peptidoglycan-induced NF-κB activation in the macrophages. These three ginsenosides also inhibited LPS-stimulated cyclooxygenase-2 and inducible NO synthase expression, and phosphorylation of NF-κB signal molecules IL-1 receptor-associated kinase 1 and tumor growth factor-β-activated kinase 1 in peritoneal macrophages. Treatment with either PRT4 or ocotillol inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, as observed by flow cytometry. They also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages, both with and without transfected MyD88 siRNA. Among the tested ginsenosides, ocotillol exhibited the strongest inhibitory effect on inflammation in LPS-stimulated macrophages via the NF-κB signaling pathway. Based on these findings, orally administered VR2 and MR2 of P. vietnamensis may be metabolized to ocotillol via PRT4, and the metabolites, particularly ocotillol, may inhibit inflammation by inhibiting the binding of LPS to TLR4 on macrophages.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South 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
authors.initials: TH
authors.lastname: Van Le
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea.
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South 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: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1, Gwanak-ro, Gwanak-gu 151-742, Seoul, South Korea.
authors.forename: Jeong Hill
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea; Department of Pharmacy, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, South Korea. Electronic address: dhkim@khu.ac.kr.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005243:Feces / Q000382:microbiology; D036145:Ginsenosides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008518:Medicine, East Asian Traditional; D008813:Mice, Inbred ICR; D064307:Microbiota; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D021381:Protein Transport; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C440499:lipopolysaccharide, Escherichia coli O111 B4; C524540:ocotillol; C000608355:pseudoginsenoside RT4; C000608354:vina-ginsenoside R2; C098043:majonoside R2
keywords: Inflammation; Macrophage; Majonoside R2; Ocotillol; Panax vietnamensis; Vina-ginsenoside R2