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Biochem Biophys Res Commun. 2019 Jan 1;508(1):97-101. doi: 10.1016/j.bbrc.2018.11.075. Epub 2018 Nov 22.

Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

Author information

1
School of Nursing, University of South China, Hengyang, Hunan, 421001, China; Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan, 421001, China.
2
School of Nursing, University of South China, Hengyang, Hunan, 421001, China.
3
School of Nursing, University of South China, Hengyang, Hunan, 421001, China; The First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, China.
4
Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr. NW, Calgary, T2N 4N1, Alberta, Canada.
5
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan, 421001, China; Department of Physiology, The Neuroscience Institute, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China. Electronic address: Y1655@163.com.
6
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,Hengyang, Hunan, 421001, China. Electronic address: tangchaoke@qq.com.

Abstract

Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.

KEYWORDS:

Atherosclerosis; LPL; MiR-590; Nobiletin

PMID:
30471854
DOI:
10.1016/j.bbrc.2018.11.075

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