Jo, A-ra Han, Hee-soo Seo, Seunghwan Shin, Ji-Sun Lee, Jae Yeol Kim, Hyoung Ja Lee, Kyung-Tae 2024-01-20T00:01:03Z 2024-01-20T00:01:03Z 2021-09-03 2017-12-01 0960-894X https://pubs.kist.re.kr/handle/201004/121941 Seeds of Carthamus tinctorius L. (Compositae) have been used in Korean traditional medicines for the treatment of cardiovascular and bone diseases. In this study, we investigated the anti-inflammatory effects of known serotonin derivatives (1-9) isolated from the ethyl acetate (EtOAc) soluble fraction from the seeds of C. tinctorius. Compound 2, identified as moschamine, most potently inhibited lipopolysaccharide (LPS)-induced production of prostaglandin E-2 (PGE(2)) and nitric oxide (NO) in RAW 264.7 macrophages. Moschamine concentration-dependently inhibited LPS-induced PGE(2) and NO production in RAW 264.7 macrophages. Consistent with these findings, moschamine suppressed the protein and mRNA levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E-2 synthase (mPGES)-1, and inducible NO synthase (iNOS), interleukin (IL)-6, and IL-1 beta. In addition, pretreatment of moschamine significantly inhibited LPS-stimulated the transcriptional activity of activator protein-1 (AP-1) and the phosphorylation of signal transducer and activator of transcription (STAT) 1/3 in RAW 264.7 macrophages. Moreover, moschamine inhibited LPS-induced the phosphorylation of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK), but it had no effect on c-Jun N-terminal kinase (JNK). These results suggest that the mechanism of anti-inflammatory activity of moschamine is associated with the downregulation of COX-2, mPGES-1, iNOS, IL-6, and IL-1 beta expression through the suppression of AP-1 and STAT1/3 activation in LPS-induced RAW 264.7 macrophages. (C) 2017 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. NF-KAPPA-B L. OIL CAKE NITRIC-OXIDE SIGNALING PATHWAY MAPK ANTIOXIDANTS EXPRESSION SEED P38 Inhibitory effect of moschamine isolated from Carthamus tinctorius on LPS-induced inflammatory mediators via AP-1 and STAT1/3 inactivation in RAW 264.7 macrophages Article 10.1016/j.bmcl.2017.10.035 1 Bioorganic & Medicinal Chemistry Letters, v.27, no.23, pp.5245 - 5251 Bioorganic & Medicinal Chemistry Letters 27 23 5245 5251 scie scopus 000415643400029 2-s2.0-85033492492 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article NF-KAPPA-B L. OIL CAKE NITRIC-OXIDE SIGNALING PATHWAY MAPK ANTIOXIDANTS EXPRESSION SEED P38 Carthamus tinctorius Serotonin derivatives Moschamine Activator protein-1 (AP-1) Signal transducer and activator of transcriptions (STATs)