Vinpocetine inhibits NF-κB-dependent inflammation via an IKK-dependent but PDE-independent mechanism

Kye Im Jeon, Xiangbin Xu, Toru Aizawa, Jae Hyang Lim, Hirofumi Jono, Dong Seok Kwon, Jun Ichi Abe, Bradford C. Berk, Jian Dong Li, Chen Yan

Research output: Contribution to journalArticlepeer-review

172 Scopus citations

Abstract

Inflammation is a hallmark of many diseases, such as atherosclerosis, chronicobstructive pulmonary disease, arthritis, infectious diseases, and cancer. Although steroids and cyclooxygenase inhibitors are effective antiinflammatory therapeutical agents, they may cause serious side effects. Therefore, developing unique antiinflammatory agents without significant adverse effects is urgently needed. Vinpocetine, a derivative of the alkaloid vincamine, has long been used for cerebrovascular disorders and cognitive impairment. Its role in inhibiting inflammation, however, remains unexplored. Here, we show that vinpocetine acts as an antiinflammatory agent in vitro and in vivo. In particular, vinpocetine inhibits TNF-α-induced NF-κB activation and the subsequent induction of proinflammatory mediators in multiple cell types, including vascular smooth muscle cells, endothelial cells, macrophages, and epithelial cells. We also show that vinpocetine inhibits monocyte adhesion and chemotaxis, which are critical processes during inflammation. Moreover, vinpocetine potently inhibits TNF-α- or LPS-induced up-regulation of proinflammatorymediators, including TNF-α, IL-1β, and macrophage inflammatory protein-2, and decreases interstitial infiltration of polymorphonuclear leukocytes in a mouse model of TNF-α- or LPS-induced lung inflammation. Interestingly, vinpocetine inhibits NF-κB-dependent inflammatory responses by directly targeting IKK, independent of its well-known inhibitory effects on phosphodiesterase and Ca2+ regulation. These studies thus identify vinpocetine as a unique antiinflammatory agent that may be repositioned for the treatment of many inflammatory diseases.

Original languageEnglish
Pages (from-to)9795-9800
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number21
DOIs
StatePublished - 25 May 2010

Keywords

  • IKK
  • Inflammation
  • NF-κB
  • Vinpocetine

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