Phenolic Compounds Isolated from Psoralea corylifolia Inhibit IL-6-induced STAT3 Activation

 

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Abstract

Inhibiting interleukin-6 (IL-6) has been postulated as an effective therapy in the pathogenesis of several inflammatory diseases. In this study, seven flavonoids were isolated from the methanol extracts of Psoralea corylifolia by bioactivity-guided fractionation. The structures of bakuchiol (1), bavachinin (2), neobavaisoflavone (3), corylifol A (4), corylin (5), isobavachalcon (6), and bavachin (7) were determined by spectroscopic analysis (¹H-, ¹³C- NMR and MS). We demonstrated that compounds 1–7 showed an inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells with IC₅₀ values of 4.57 ± 0.45, 3.02 ± 0.53, 2.77 ± 0.02, 0.81 ± 0.15, 1.37 ± 0.45, 2.45 ± 0.13, and 4.89 ± 0.05 µΜ, respectively. These compounds also inhibited STAT3 phosphorylation induced by IL-6 in Hep3B cells. Overall, several flavonoids from P. corylifolia might be useful remedies for treating inflammatory diseases by inhibiting IL-6-induced STAT3 activation and phosphorylation.

• References

• 1 Luger TA, Schwarz T, Krutmann J, Kirnbauer R, Neuner P, Kock A, Urbanski A, Borth W, Schauer E. Interleukin-6 is produced by epidermal cells and plays an important role in the activation of human T-lymphocytes and natural killer cells. Ann NY Acad Sci 2008; 557: 405-414
  CrossrefPubMedGoogle Scholar
• 2 Neveu WA, Allard JB, Dienz O, Wargo MJ, Ciliberto G, Whittaker LA, Rincon M. IL-6 is required for airway mucus production induced by inhaled fungal allergens. J Immunol 2009; 183: 1732-1738
  CrossrefPubMedGoogle Scholar
• 3 Morishima A, Marui A, Shimamoto T, Saji Y, Nishina T, Komeda M. A case of interleukin-6-producing cardiac myxoma resembling multicentric Castlemanʼs disease. J Thorac Cardiovasc Surg 2009; 138: 499-501
  CrossrefPubMedGoogle Scholar
• 4 Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis: evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 2009; 68: 1580-1584
  CrossrefPubMedGoogle Scholar
• 5 Mori A, Toyoshima N, Saito M, Oka T, Irie T, Morioka M. Hypercalcemia and multiple osteolytic lesions associated with proinflammatory cytokines in a patient with acute lymphoblastic leukemia. Rinsho Ketsueki 2007; 48: 559-564
  PubMedGoogle Scholar
• 6 Fulciniti M, Hideshima T, Vermot-Desroches C, Pozzi S, Nanjappa P, Shen Z, Patel N, Smith ES, Wang W, Prabhala R, Tai YT, Tassone P, Anderson KC, Munshi NC. A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clin Cancer Res 2009; 15: 7144-7152
  CrossrefPubMedGoogle Scholar
• 7 Bhagat K, Valance P. Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo . Circulation 1997; 96: 3042-3047
  CrossrefPubMedGoogle Scholar
• 8 Zhu YP. Chinese material medica: chemistry, pharmacology and applications. Amsterdam: Harwood Academic Publishers; 1998: 609-612
  Google Scholar
• 9 Yin S, Fan CQ, Wang Y, Dong L, Yue JM. Antibacterial prenylflavone derivatives from Psoralea corylifolia and their structure-activity relationship study. Biol Med Chem 2004; 12: 4387-4392
  CrossrefPubMedGoogle Scholar
• 10 Lee MH, Kim JY, Ryu JH. Prenylflavones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of IκBα degradation in activated microglial cells. Biol Pharm Bull 2005; 28: 2253-2257
  CrossrefPubMedGoogle Scholar
• 11 Haraguchi H, Inoue J, Tamura Y, Mizutani K. Inhibition of mitochondrial lipid peroxidation by bakuchiol, a meroterpene from Psoralea corylifolia . Planta Med 2000; 66: 569-571
  Article in Thieme ConnectPubMedGoogle Scholar
• 12 Kim YC, Oh H, Kim BS, Kang TH, Ko EK, Han YM, Kim BY, Ahn JS. In vitro protein tyrosine phosphatase 1B inhibitory phenols from the seeds of Psoralea corylifolia . Planta Med 2005; 71: 87-89
  Article in Thieme ConnectPubMedGoogle Scholar
• 13 Park EJ, Zhao YZ, Kim YC, Sohn DH. Protective effect of (S)-bakuchiol from Psoralea corylifolia on rat liver injury in vitro and in vivo . Planta Med 2005; 71: 508-513
  Article in Thieme ConnectPubMedGoogle Scholar
• 14 Choi JH, Rho MC, Lee SW, Choi JN, Kim K, Song GY, Kim YK. Bavachin and isobavachacone, acyl-coenzyme A: cholesterol acyltransferase inhibitors from Psoralea corylifolia . Arch Pharm Res 2008; 31: 1419-1423
  CrossrefPubMedGoogle Scholar
• 15 Kim YJ, Lee H, Park E, Shim SH. Inhibition of human 20S proteasome by compounds from seeds of Psoralea corylifola . Bull Korean Chem Soc 2009; 30: 1867-1869
  CrossrefPubMedGoogle Scholar
• 16 Li HC, Zhang GY. Inhibitory effect of genistein on activation of STAT3 induced by brain ischemia/reperfusion in rat hippocampus. Acta Pharmacol Sin 2003; 24: 1131-1136
  PubMedGoogle Scholar
• 17 Yan SF, Zou YS, Gao Y, Zhai C, Mackman N, Lee SL, Milbrandt J, Pinsky D, Kisiel W, Stern D. Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia. Proc Natl Acad Sci USA 1998; 95: 8298-8303
  CrossrefPubMedGoogle Scholar

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