Rotundarpene inhibits TNF-α-induced activation of the Akt, mTOR, and NF-κB pathways, and the JNK and p38 associated with production of reactive oxygen species

• Published in: Molecular and cellular biochemistry Vol. 434; no. 1-2; pp. 113 - 125
• Main Authors: Kim, Arum, Nam, Yoon Jeong, Shin, Yong Kyoo, Lee, Min Sung, Sohn, Dong Suep, Lee, Chung Soo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2017
• Subjects: Biochemistry; Biomedical and Life Sciences; Cardiology; Life Sciences; Medical Biochemistry; Oncology; Keratinocytes; Inflammatory mediator production; JNK and p38-MAPK; Tumor necrosis factor-α; Rotundarpene; Akt, mTOR and NF-κB pathways
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-017-3041-x

Ilex Rotunda Thunb has been shown to have anti-inflammatory and antioxidant effects. In human keratinocytes, we investigated the effect of rotundarpene (4-caffeoyl-3-methyl-but-2-ene-1,4-diol) on the TNF-α-stimulated production of inflammatory mediators in relation to the Akt, mTOR, and NF-κB pathways, and the JNK and p38-MAPK. Rotundarpene, Akt inhibitor, Bay 11-7085, rapamycin, and N -acetylcysteine inhibited the TNF-α-stimulated production of cytokines and chemokines, increase in the levels of p-Akt and mTOR, activation of NF-κB, and production of reactive oxygen species in keratinocytes. TNF-α treatment induced phosphorylation of the JNK and p38-MAPK. Inhibitors of the c-JNK (SP600125) and p38-MAPK (SB203580) reduced the TNF-α-induced production of inflammatory mediators, binding of NF-κB to DNA, and activation of the JNK and p38-MAPK in keratinocytes. The results show that rotundarpene may reduce the TNF-α-stimulated inflammatory mediator production by suppressing the reactive oxygen species-dependent activation of the Akt, mTOR, and NF-κB pathways, and activation of the JNK and p38-MAPK in human keratinocytes. Additionally, rotundarpene appears to attenuate the Akt, mTOR, and NF-κB pathways and the JNK and p38-MAPK-mediated inflammatory skin diseases.