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  2. Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products

Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products

  • Int Immunopharmacol. 2014 Jul;21(1):56-62. doi: 10.1016/j.intimp.2014.04.016.
Hui Shi 1 Juan Ma 2 Chunliu Mi 1 Jing Li 1 Fei Wang 2 Jung Joon Lee 3 Xuejun Jin 4
Affiliations

Affiliations

  • 1 Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China; Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, Department of Chemistry, Yanbian University, Yanji 133002, Jilin Province, China.
  • 2 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China.
  • 3 Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: jjlee0908@gmail.com.
  • 4 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China; Molecular Cancer Research Center, Yanbian University, Yanji 133002, Jilin Province, China. Electronic address: xjjin@ybu.edu.cn.
Abstract

The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, Apoptosis, and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified amorfrutin A as an inhibitor of NF-κB activation from the fruits of Amorpha fruticosa L. In present study, this compound significantly inhibited the TNF-α-induced expression of NF-κB reporter gene. Further analysis revealed that amorfrutin A was a potent inhibitor of NF-κB activation by the suppression of TNF-α-induced inhibitor of κBα (IκBα) degradation, p65 nuclear translocation, and DNA-binding activity of NF-κB. We also demonstrated that pretreatment of cells with this compound prevented the TNF-α-induced expression of NF-κB target genes, such as antiapoptosis (cIAP-1 and FLIP), proliferation (COX-2 and cyclinD1), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-α, IL-8, and MCP1). Furthermore, our results suggest that amorfrutin A potentiates TNF-α-induced Apoptosis. Taken together, amorfrutin A could be a valuable candidate for the intervention of NF-κB-dependent pathological conditions such as inflammation.

Keywords

Amorfrutin A; Apoptosis; Inflammation; IκBα; Nuclear factor-κB (NF-κB).

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