Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 3, pp 271–283 | Cite as

Apigenin reduces the Toll-like receptor-4-dependent activation of NF-κB by suppressing the Akt, mTOR, JNK, and p38-MAPK

Original Article


Flavone apigenin has an anti-inflammatory effect. We assessed whether apigenin may reduce the inflammatory mediator production, which is regulated by the Toll-like receptor-4-dependent activation of the Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK in HEK001 keratinocytes and primary keratinocytes. Apigenin, the Akt inhibitor, Bay 11-7085, and N-acetylcysteine inhibited the lipopolysaccharide-stimulated production of cytokines IL-1β and IL-6 and chemokines CCL17 and CCL27; the expression of cyclooxygenase-2; the increase in the levels of Toll-like receptor-4, phosphorylated Akt, and mTOR; the activation of NF-κB; the activation of the JNK and p38-MAPK; and the production of reactive oxygen/nitrogen species in keratinocytes. Inhibitors of the c-JNK (SP600125) and p38-MAPK (SB203580) reduced lipopolysaccharide-induced production of inflammatory mediators and activation of the JNK and p38-MAPK in keratinocytes. These results show that apigenin may inhibit the lipopolysaccharide-caused inflammatory mediator production in keratinocytes by reducing the Toll-like receptor-4-dependent activation of Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK. The suppressive effect of apigenin may be achieved by the inhibition of reactive oxygen/nitrogen species production. Additionally, apigenin appears to reduce the Akt, mTOR, and NF-κB pathway- and the JNK and p38-MAPK-mediated inflammatory skin diseases.


Keratinocytes Lipopolysaccharide Apocynin Toll-like receptor-4 Akt, mTOR, and NF-κB pathways JNK and p38-MAPK Inflammatory mediator production 


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Pharmacology, College of MedicineChung-Ang UniversitySeoulSouth Korea
  2. 2.The BK21plus Skin Barrier Network Human Resources Development TeamChung-Ang UniversitySeoulSouth Korea

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