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2000
Volume 21, Issue 6
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Exogenous substances modulate metabolism by regulating the expression and function of UDP-glycosyltransferases (UGTs). However, the exact mechanism in the intestine was rarely understood. Herein, we explored the effects of representative flavonoids and organic acids on the regulation of UGT1A1.

Methods

MTT assays and western blot analysis were used to explore the effect of polyphenols. X-ray diffraction was used to reveal the catalytic mechanisms of UGTs.

Results

MTT assays showed that these compounds basically had almost no cytotoxicity, even in concentrations up to 200 μM. However, through western blot assays, UGT1A1 expression was increased after being treated with liquiritigenin and caffeic acid. Furthermore, liquiritigenin and caffeic acid enhanced the nuclear translocation of Nrf2. Moreover, a 2.5-Å crystal structure of the complex containing UGTs C-terminal domain and organic acid was solved, and the UDPGA binding pocket could be occupied by organic acid, suggesting the enzyme activity might be impaired by organic acid.

Conclusion

Above all, liquiritigenin and caffeic acid maintained the metabolism balance by upregulating the expression of UGT1A1 Nrf2 activation and inhibiting the enzyme activity in Caco-2 cells.

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Flavonoids and Organic Acids Affect Phase II Metabolism based on the Regulation of UGT1A1 Expression and Function
Curr. Computeraided Drug Des. 21, 831 (2025); https://doi.org/10.2174/0115734099300793240509103320
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  • Article Type:     Research Article
Keyword(s): Crystal structure; flavonoids; mechanism; Nrf2; polyphenols; UGTs

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