In vitro and in vivo anti-inflammatory activities of Polygonum hydropiper methanol extract

• Published in: Journal of ethnopharmacology Vol. 139; no. 2; pp. 616 - 625
• Main Authors: Yang, Yanyan, Yu, Tao, Jang, Hyun-Jae, Byeon, Se Eun, Song, Song-Yi, Lee, Byoung-Hee, Rhee, Man Hee, Kim, Tae Woong, Lee, Jaehwi, Hong, Sungyoul, Cho, Jae Youl
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 31-01-2012
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory effects; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - immunology; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - prevention & control; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Dextran Sulfate; Dinoprostone - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Inflammation Mediators - metabolism; Interleukin-1 Receptor-Associated Kinases - antagonists & inhibitors; Interleukin-1 Receptor-Associated Kinases - metabolism; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Methanol - chemistry; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plants, Medicinal; Polygonaceae; Polygonum - chemistry; Polygonum hydropiper L; Prostaglandin E2; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; RNA, Messenger - metabolism; Signal Transduction - drug effects; Solvents - chemistry; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - metabolism; Syk Kinase; Time Factors; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transfection; Tumor Necrosis Factor-alpha - metabolism; Tumour necrosis factor-α; NO; ATF2; Tumour necrosis factor-α; JNK; Prostaglandin E2; MTT; AP-1; MyD88; LPS; NF-κB; (TNF)-α; CREB; IRAK1; TAK1; PI3K; RT-PCR; iNOS; TLR; EIA; PDK1; PGE2; Syk; DSS; Polygonaceae; IKK; Akt; MAPK; MKK; Anti-inflammatory effects; COX; TRAF6; Nitric oxide; Polygonum hydropiper L; Ph-ME; TRIF; ERK; ELISA
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2011.12.003

Ph-ME has a potent anti-inflammatory activity mediated by Src/Syk/NF-κB, and IRAK1/AP-1 inhibitory properties (Fig. 10).
Polygonum hydropiper L. (Polygonaceae) has been traditionally used to treat various inflammatory diseases such as rheumatoid arthritis. However, no systematic studies on the anti-inflammatory actions of Polygonum hydropiper and its inhibitory mechanisms have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 99% methanol extracts (Ph-ME) of this plant.
The effects of Ph-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages were investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, were elucidated by analyzing the activation of transcription factors and their upstream signalling, and by evaluating the kinase activities of target enzymes. Additionally, a dextran sulphate sodium (DSS)-induced colitis model was employed to see whether this extract can be used as an orally available drug.
Ph-ME dose-dependently suppressed the release of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin (PG)E2, in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ph-ME inhibited mRNA expression of pro-inflammatory genes such as inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, activator protein (AP-1), and cAMP responsive element binding protein (CREB), and simultaneously inhibited its upstream inflammatory signalling cascades, including cascades involving Syk, Src, and IRAK1. Consistent with these findings, the extract strongly suppressed the kinase activities of Src and Syk. Based on HPLC analysis, quercetin, which inhibits NO and PGE2 activities, was found as one of the active ingredients in Ph-ME.
Ph-ME exerts strong anti-inflammatory activity by suppressing Src/Syk/NF-κB and IRAK/AP-1/CREB pathways, which contribute to its major ethno-pharmacological role as an anti-gastritis remedy.