title: HangAmDan-B, an ethnomedicinal herbal mixture, suppresses inflammatory responses by inhibiting Syk/NF-κB and JNK/ATF-2 pathways.
abstract: HangAmDan-B (HAD-B) is a powdered mixture of eight ethnopharmacologically characterized folk medicines that is prescribed for solid masses and cancers in Korea. In view of the finding that macrophage-mediated inflammation is a pathophysiologically important phenomenon, we investigated whether HAD-B modulates inflammatory responses and explored the associated molecular mechanisms. The immunomodulatory activity of HAD-B in toll-like receptor-activated macrophages induced by lipopolysaccharide (LPS) was assessed by measuring nitric oxide (NO) and prostaglandin E(2) (PGE(2)) levels. To identify the specific transcription factors (such as nuclear factor [NF]-κB and signaling enzymes) targeted by HAD-B, biochemical approaches, including kinase assays and immunoblot analysis, were additionally employed. HAD-B suppressed the production of PGE(2) and NO in LPS-activated macrophages in a dose-dependent manner. Furthermore, the extract ameliorated HCl/EtOH-induced gastritis symptoms. Moreover, HAD-B significantly inhibited LPS-induced mRNA expression of inducible NO synthase and cyclooxygenase (COX)-2. Interestingly, marked inhibition of NF-κB and activating transcription factor was observed in the presence of HAD-B. Data from direct kinase assays and immunoblot analysis showed that HAD-B suppresses activation of the upstream signaling cascade involving spleen tyrosine kinase, Src, p38, c-Jun N-terminal kinase, and transforming growth factor β-activated kinase 1. Finally, kaempferol, but not quercetin or resveratrol was identified as a bioactive compound in HAD-B. Therefore, our results suggest that HAD-B possesses anti-inflammatory activity that contributes to its anticancer property.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Korea.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Moh
authors.forename: Sang-Bom
authors.initials: SB
authors.lastname: Kim
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.forename: Yeon-Weol
authors.initials: YW
authors.lastname: Lee
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Cho
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase
chemical_list: D051698:Activating Transcription Factor 2; D000893:Anti-Inflammatory Agents; C497106:Atf2 protein, mouse; D004365:Drugs, Chinese Herbal; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D048670:MAP Kinase Kinase 4