title: Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis.
abstract: Ginsenoside Rg1, one of the main constituents of Panax ginseng, exhibits anti-inflammatory effect. In a preliminary study, it was observed that ginsenoside Rg1 was metabolized to 20(S)-protopanaxtriol via ginsenosides Rh1 and F1 by gut microbiota. We further investigated the anti-inflammatory effects of ginsenoside Rg1 and its metabolites in vitro and in vivo. Ginsenosides Rg1, Rh1, and 20(S)-protopanaxtriol inhibited the activation of NF-κB activation, phosphorylation of transforming growth factor beta-activated kinase 1 and interleukin (IL)-1 receptor-associated kinase, and expression of tumor necrosis factor-α and IL-1β in lipopolysaccharide (LPS)-stimulated macrophages. They also inhibited the binding of LPS to toll-like receptor 4 on the macrophages. Orally administered ginsenoside Rg1, Rh1, or 20(S)-protopanaxtriol inhibited 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colon shortening, myeloperoxidase activity, and expression of IL-1β, IL-17, and tumor necrosis factor-α in mice with TNBS-induced colitis. They did not only inhibit TNBS-induced NF-κB activation, but also restored TNBS-induced Th17/Treg imbalance. They restored IL-10 and Foxp3 expression. Moreover, they inhibited Th17 cell differentiation in vitro. Of these metabolites, in vitro and in vivo anti-inflammatory effect of 20(S)-protopanaxtriol was the most potent, followed by Rh1. These findings suggest that ginsenoside Rg1 is metabolized to 20(S)-protopanaxtriol via ginsenosides Rh1 and F1 and these metabolites particularly 20(S)-protopanaxtriol, may ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-ku, Seoul 130-701, Republic of 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-ku, Seoul 130-701, Republic of Korea.
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Jeong
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-ku, Seoul 130-701, Republic of Korea.
authors.forename: Su-Hyeon
authors.initials: SH
authors.lastname: Eun
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-ku, Seoul 130-701, Republic of 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 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D036145:Ginsenosides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D012502:Sapogenins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D012502:Sapogenins; D014409:Tumor Necrosis Factor-alpha; C507965:ginsenoside 20S-protopanaxatriol; C425564:ginsenoside Rh1; D014302:Trinitrobenzenesulfonic Acid; C035054:ginsenoside Rg1
keywords: 20(S)-protopanaxtriol; Colitis; Ginsenoside Rg1; Inflammation; Macrophage; TH17 cell