In vivo and in vitro anti-inflammatory activities of Persicaria chinensis methanolic extract targeting Src/Syk/NF-κB

• Published in: Journal of ethnopharmacology 2015-01, Vol.159, p.9-16
• Main Authors: Hossen, Muhammad Jahangir, Baek, Kwang-Soo, Kim, Eunji, Yang, Woo Seok, Jeong, Deok, Kim, Jun Ho, Kweon, Dae-Hyuk, Yoon, Deok Hyo, Kim, Tae Woong, Kim, Jong-Hoon, Cho, Jae Youl
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-inflammatory effect; Cell Line; Cell Survival - drug effects; Cells, Cultured; Ethanol; Flavonoids - isolation & purification; Flavonoids - pharmacology; Flavonoids - therapeutic use; Gastritis - chemically induced; Gastritis - drug therapy; HEK293 Cells; Humans; Hydrochloric Acid; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; Lipopolysaccharides; Macrophages; Male; Methanol - chemistry; Mice, Inbred C57BL; Mice, Inbred ICR; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; Nitric oxide; Persicaria chinensis (Polygonaceae); Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Polygonum; Prostaglandin E2; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Quercetin; Solvents - chemistry; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - metabolism; Syk Kinase
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2014.10.064

Persicaria chinensis L. (Polygonaceae) [also synonym as Polygonum chimnense L.] has been used as Chinese traditional medicine to treat ulcer, eczema, stomach ache, and various inflammatory skin diseases. Due to no molecular pharmacological evidence of this anti-inflammatory herbal plant, we investigated the inhibitory mechanisms and target proteins contributing to the anti-inflammatory responses of the plant by using its methanolic extract (Pc-ME). We used lipopolysaccharide (LPS)-treated macrophages and a murine HCl/EtOH-induced gastritis model to evaluate the anti-inflammatory activity of Pc-ME. HPLC analysis was employed to identify potential active components of this extract. Molecular approaches including kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes were used to confirm target enzymes. Pc-ME inhibited LPS-induced nitric oxide and prostaglandin E2 release by RAW264.7 macrophages and ameliorated HCl/EtOH-induced gastric ulcers in mice. The nuclear translocation of NF-κB (p65 and p50) was suppressed by Pc-ME. Phosphorylation of Src and Syk, their kinase activities, and formation of the signaling complex of these proteins were repressed by Pc-ME. Phosphorylation of p85 and Akt induced by Src or Syk overexpression was blocked by Pc-ME. In the mouse gastritis model, orally administered Pc-ME suppressed the increased phosphorylation of IκBα, Αkt, Src, and Syk. Caffeic acid, kaempferol, and quercetin, identified as major anti-inflammatory components of Pc-ME by HPLC, displayed strong nitric oxide inhibitory activity in LPS-treated macrophages. Pc-ME might play a pivotal ethnopharmacologic role as an anti-inflammatory herbal medicine by targeting Syk and Src kinases and their downstream transcription factor NF-κB. [Display omitted]