HangAmDan-B, an Ethnomedicinal Herbal Mixture, Suppresses Inflammatory Responses by Inhibiting Syk/NF-kappa B and JNK/ATF-2 Pathways

Authors Yu, Tao; Moh, Sang Hyun; Kim, Sang-Bom; Yang, Yanyan; Kim, Eunji; Lee, Yeon-Weol; Cho, Chong-Kwan; Kim, Kyung-Hee; Yoo, Byong Chul; Cho, Jae Youl; Yoo, Hwa-Seung

Journal JOURNAL OF MEDICINAL FOOD , JAN 2013,1:16

DOI 10.1089/jmf.2012.2374 PubMed 23256447

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]-kappa B 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-kappa B 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 beta-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.