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  2. Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway

Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway

  • Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):882-890. doi: 10.1016/j.bbadis.2017.12.033.
Yuyu Yang 1 Xueyan Li 1 Liying Peng 1 Lin An 1 Ningyuan Sun 1 Xuewen Hu 1 Ping Zhou 1 Yong Xu 2 Ping Li 3 Jun Chen 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • 2 Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. Electronic address: liping2004@126.com.
  • 4 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. Electronic address: chenj2002cpu@126.com.
Abstract

NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root of Salvia miltiorrhiza Bge., a traditional Chinese medicine that has been used for the treatment of several cardiovascular diseases for many years. This study was aimed to test the potential role of Tan C against macrophage foam cell formation and to explore the underlying mechanism. Firstly, we observed that Tan C markedly suppressed oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation. Then, we found that Tan C was an activator of both Nrf2 and Sirtuin 1 (SIRT1) in macrophages. Nrf2 and SIRT1 synergistically activated the transcription of anti-oxidant peroxiredoxin 1 (Prdx1) after Tan C treatment. More important, we demonstrated that silencing of Prdx1 promoted oxLDL-induced macrophage foam cell formation. Prdx1 upregulated adenosine triphosphate-binding cassette (ABC) transporter A1 (ABCA1) expression and decreased intracellular lipid accumulation. Furthermore, Tan C ameliorated oxLDL induced macrophage foam cell formation in a Prdx1-dependent manner. These observations suggest that Tan C protects macrophages from oxLDL induced foam cell formation via activation of Prdx1/ABCA1 signaling and that Prdx1 may be a novel target for therapeutic intervention of atherosclerosis.

Keywords

ABCA1; Macrophage foam cell formation; Nrf2; Peroxiredoxin 1; Tanshindiol C.

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