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

• DOI: 10.1073/pnas.0914414107
• Publication Date: 2010-05-07T02:20:36Z
• Authors: 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
• Keywords: Vinpocetine; Proinflammatory cytokine; IκB kinase

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