title: Inhibitory effects of sulfated 20(S)-ginsenoside Rh2 on the release of pro-inflammatory mediators in LPS-induced RAW 264.7 cells.
abstract: Ginsenoside Rh2 is one of the most important ginsenosides in ginseng with anti-inflammatory and antitumor effects. However, the extremely poor oral bioavailability induced by its low water solubility greatly limits the potency of Rh2 in vivo. In the previous study, we sulfated 20(S)-ginsenoside Rh2 with chlorosulfonic acid and pyridine method, and got one novel derivative, Rh2-B1, with higher water solubility and greater immunologic enhancement than Rh2. However, the anti-inflammatory effect of Rh2-B1 remains unclear. We therefore investigated the effects of Rh2-B1 on lipopolysaccharide (LPS)-induced proinflammatory mediators in RAW 264.7 macrophages. We found that Rh2-B1 dramatically inhibited LPS-induced overproduction of nitric oxide, prostaglandin E2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Consistently, the protein and mRNA expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were remarkably decreased by Rh2-B1. In addition, Rh2-B1 significantly suppressed the phosphorylations of p38, c-Jun N-terminal kinase, and extracellular signal receptor-activated kinase 1/2 induced by LPS. Rh2-B1 was further shown to inhibit NF-κB p65 translocation into the nucleus by suppressing IκBα degradation. In conclusion, we demonstrate that Rh2-B1 inhibits the release of LPS-induced pro-inflammatory mediators through blocking mitogen-activated protein kinases and NF-κB signaling pathways, suggesting that sulfated ginsenosides could be potential agents for anti-inflammatory therapies.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, No. 5333 Xi'an Road, Changchun, Jilin 130062, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Yi
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Bi
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Shen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wei
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Dong
authors.forename: Huan-Li
authors.initials: HL
authors.lastname: Bai
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Song
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Qin
authors.forename: Shuang
authors.initials: S
authors.lastname: Lv
authors.forename: Shuai-Cheng
authors.initials: SC
authors.lastname: Wu
authors.forename: Ben-Dong
authors.initials: BD
authors.lastname: Fu
authors.forename: Xu-Bin
authors.initials: XB
authors.lastname: Wei
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry* / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013431:Sulfates / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D036145:Ginsenosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013431:Sulfates; C055305:ginsenoside Rh2; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases