Gene interactions and pathways from curated databases and text-mining
Int Immunopharmacol 2010, PMID: 20153843

The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-kappaB activation.

Funakoshi-Tago, Megumi; Nakamura, Kei; Tsuruya, Rina; Hatanaka, Masashi; Mashino, Tadahiko; Sonoda, Yoshiko; Kasahara, Tadashi

Glycyrrhiza inflata has been used as a traditional medicine with anti-inflammatory activity. Previously, we reported that a major component, Licochalcone A, potently inhibited TNFalpha-induced NF-kappaB activation by inhibiting IKKbeta activation. In this study, we investigated whether the fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is required for its inhibitory effect of NF-kappaB activation. Interestingly, reduced Licochalcone A, which lacks a double bond, failed to inhibit TNFalpha-induced NF-kappaB activation. Whereas Licochalcone A potently inhibited TNFalpha-induced IKK activation, IkappaBalpha degradation, nuclear localization of NF-kappaB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A. In addition, TNFalpha-induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced Licochalcone A. As a result, culture media pretreated with Licochalcone A but not reduced Licochalcone A following TNFalpha stimulation significantly inhibited the chemotactic activity of neutrophils. Furthermore, acute carrageenan-induced paw edema in mice was markedly inhibited by administration of Licochalcone A but not reduced Licochalcone A. Taken together, it is suggested that Licochalcone A is a promising anti-inflammatory drug in vivo and its fixed structure is critical for anti-inflammatory activity.

Diseases/Pathways annotated by Medline MESH: Edema
Document information provided by NCBI PubMed

Text Mining Data

NF-kappaB → TNFalpha: " Previously, we reported that a major component, Licochalcone A, potently inhibited TNFalpha induced NF-kappaB activation by inhibiting IKKbeta activation "

NF-kappaB → IKKbeta: " Previously, we reported that a major component, Licochalcone A, potently inhibited TNFalpha induced NF-kappaB activation by inhibiting IKKbeta activation "

NF-kappaB → TNFalpha: " Interestingly, reduced Licochalcone A, which lacks a double bond, failed to inhibit TNFalpha induced NF-kappaB activation "

IKK → TNFalpha: " Whereas Licochalcone A potently inhibited TNFalpha induced IKK activation, IkappaBalpha degradation, nuclear localization of NF-kappaB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A "

NF-kappaB → TNFalpha: " Whereas Licochalcone A potently inhibited TNFalpha induced IKK activation, IkappaBalpha degradation, nuclear localization of NF-kappaB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A "

IkappaBalpha → TNFalpha: " Whereas Licochalcone A potently inhibited TNFalpha induced IKK activation , IkappaBalpha degradation, nuclear localization of NF-kappaB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A "

CCL2/MCP-1 → TNFalpha: " In addition, TNFalpha induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced Licochalcone A "

CCL2/MCP-1 → TNFalpha: " In addition, TNFalpha induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced Licochalcone A "

CXCL1/KC → TNFalpha: " In addition, TNFalpha induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC , was clearly inhibited by Licochalcone A but not reduced Licochalcone A "

Manually curated Databases

No curated data.