期刊
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
卷 54, 期 3, 页码 145-150出版社
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION
DOI: 10.3164/jcbn.14-9
关键词
flavonoid; glucuronide; macrophage; beta-glucuronidase; mitochondria
资金
- Ministry of Education, Culture, Sports, Science, and Technology
- Ministry of Agriculture, Forestry and Fishery Food Project, Japan
- Center of Excellence Program in the 21st Century in Japan
- Grants-in-Aid for Scientific Research [26292069] Funding Source: KAKEN
Epidemiological and experimental studies suggest that the consumption of flavonoid-rich diets decreases the risk of various chronic diseases such as cardiovascular diseases. Although studies on the bioavailability of flavonoids have been well-characterized, the tissue and cellular localizations underlying their biological mechanisms are largely unknown. The development and application of novel monoclonal antibodies revealed that macrophages could be the major target of dietary flavonoids in vivo. Using macrophage-like cell lines in vitro, we examined the molecular basis of the interaction between the macrophages and flavonoids, especially the glucuronide metabolites. We have found that extracellular beta-glucuronidase secreted from macrophages is essential for the bioactivation of the glucuronide conjugates into the aglycone, and that the enzymatic activity, which requires an acidic pH, is promoted by the increased secretion of lactate in response to the mitochondrial dysfunction. This review describes our recent findings indicating the molecular mechanisms responsible for the anti-inflammatory activity of dietary flavonoids within the inflammation sites. We propose that the extracellular activity of beta-glucuronidase associated with the status of the mitochondrial function in the target cells might be important biomarkers for the specific sites where the glucuronides of dietary flavonoids can act as anti-atherosclerotic and anti-inflammatory agents in vivo.
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