Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid

Abstract

Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E 2 from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.

Tabebuia impetiginosa: A Comprehensive Review on Traditional Uses, Phytochemistry, and Immunopharmacological Properties

“…Transfection was performed using HEK293 cells with the IRAK1 gene to validate the results, and treatment with AQCA suppressed phosphorylation of p38 protein without altering FLAG and IRAK1 protein levels. Taken together, these findings suggest that downregulation of IRAK1 by AQCA contributes to an anti-inflammatory effect [ 59 ]. Results are summarized in a pathway chart ( Figure 3 ).…”

“…Park et al [ 59 ] investigated the effect of anthraquinone, a main component of T. impetiginosa . They specifically focused on anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid) (AQCA: 1 ) and discovered through immunoblotting that an inhibitor of IκB (IKK) and IκBα decreased when treated with 100 μM of AQCA in LPS-induced RAW264.7 cells.…”

“…They specifically focused on anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid) (AQCA: 1 ) and discovered through immunoblotting that an inhibitor of IκB (IKK) and IκBα decreased when treated with 100 μM of AQCA in LPS-induced RAW264.7 cells. They repeated the kinase assay and found that Syk and Src were inhibited by treatment with AQCA [ 59 ].…”

Anti-inflammatory effect of torilidis fructus ethanol extract through inhibition of Src

“…Peritoneal exudates were obtained from 6-week-old male ICR mice via lavage for 4 d after 1 mL sterilized 4% thioglycollate broth (Difco Laboratories, Detroit, MI) was injected intraperitoneally (Park, Son, Kim, et al. 2016 ).…”

“… 2016 ; Park, Son, Kim, et al. 2016 ). This transduction activates certain transcription factors, nuclear factor (NF)-κB, and activator protein (AP)-1, which form transcription initiation complexes and trigger inflammatory gene expression, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumour necrosis factor (TNF)-α (Byeon et al.…”