ReferenceID 5867
Molecular mechanism for nobiletin to enhance ABCA1/G1 expression in mouse macrophages
Atherosclerosis
BACKGROUND AND AIMS: Nobiletin (NOB), a functional ingredient found in citrus peel, is said to act against diabetes, obesity, and atherosclerosis. It has been reported to activate AMPK pathway, as well as increase SREBP1
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Record Fields
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- Reference Id
- 5867
- Evidence Id
- 22457
- Core Evidence Id
- 22457
- Source Reference Id
- 5001
- Herb2 Reference Id
- HBREF005798
- Subject Paper Key
- HBIN037171_32062137
- Pubmed Id
- 32062137
- Doi
- 10.1016/j.atherosclerosis.2020.01.024
- Paper Title
- Molecular mechanism for nobiletin to enhance ABCA1/G1 expression in mouse macrophages
- Paper Abstract
- BACKGROUND AND AIMS: Nobiletin (NOB), a functional ingredient found in citrus peel, is said to act against diabetes, obesity, and atherosclerosis. It has been reported to activate AMPK pathway, as well as increase SREBP1c, PPARalpha and PPARgamma expression. However, no molecular mechanism has been elucidated to be able to integrate these sporadic findings with some controversies to lead to concrete outcomes. In this study, regulation of HDL biogenesis by NOB was investigated modulating ABCA1 and ABCG1 expression. METHODS AND RESULTS: Regulation of ABCA1/G1 by NOB was investigated in mouse macrophages J774.1. NOB increased mRNA and protein levels of ABCA1/G1, and cell cholesterol release by these factors. It also increased mRNA of PPARgamma and LXRalpha but not PPARalpha. The increase in ABCA1/G1 mRNA levels by NOB was suppressed by antagonists of PPARgamma and LXRalpha. The increase in PPARgamma mRNA levels by NOB was suppressed by an LXRalpha antagonist, and the increase in LXRalpha mRNA levels was suppressed by a PPARgamma antagonist. NOB increased CD36 mRNA and this was suppressed by an LXRalpha antagonist. The increase in ABCA1 mRNA by a PPARgamma agonist was also suppressed by an LXRalpha antagonist. NOB did not influence LPL1 mRNA expression levels. NOB stimulated AMPK phosphorylation, and the increase in ABCA1/G1, LXRalpha and PPARgamma mRNA levels and ABCA1/G1 protein levels by NOB was reversed by an AMPK inhibitor. AMPK siRNA suppressed ABCA1 expression. CONCLUSIONS: NOB activates AMPK and subsequently LXRalpha to promote the expression of ABCA1 and ABCG1, and an LXRalpha - PPARgamma loop pathway amplifies these signals.
- Journal
- Atherosclerosis
- Publish Year
- 2020
- Experiment Subject
- mouse; mouse macrophages j774.1
- Experiment Type
- Cell Experiment
- Phenotype Related
- Obesity; Diabetes; Atherosclerosis
- Paper Title Cn
- Paper Title En
- Molecular mechanism for nobiletin to enhance ABCA1/G1 expression in mouse macrophages
- Bilingual Status
- semi_complete