The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts

Changda Liu, Nan Yang, Xiaoke Chen, Jody R Tversky, Jixun Zhan, Mirna Chehade, Rachel L. Miller, Xiu Min Li

Research output: Contribution to journalArticle

Abstract

Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4′-dihydroxyflavone (7,4′-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4′-DHF compared with other compounds from G. uralensis, to compare 7,4′-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4′-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4′-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4′-DHF co-culture. 7,4′-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4′-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production.

Original languageEnglish (US)
Pages (from-to)449-458
Number of pages10
JournalPhytotherapy Research
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2017

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Flavonoids
Dexamethasone
Fibroblasts
Glycyrrhiza uralensis
Inflammation
Lung
Chemotactic Factors
Coculture Techniques
Interleukin-4
Glucocorticoids
Asthma

Keywords

  • corticosteroids
  • Glycyrrhiza uralensis
  • lung fibroblasts
  • STAT6

ASJC Scopus subject areas

  • Pharmacology

Cite this

The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts. / Liu, Changda; Yang, Nan; Chen, Xiaoke; Tversky, Jody R; Zhan, Jixun; Chehade, Mirna; Miller, Rachel L.; Li, Xiu Min.

In: Phytotherapy Research, Vol. 31, No. 3, 01.03.2017, p. 449-458.

Research output: Contribution to journalArticle

Liu, Changda ; Yang, Nan ; Chen, Xiaoke ; Tversky, Jody R ; Zhan, Jixun ; Chehade, Mirna ; Miller, Rachel L. ; Li, Xiu Min. / The Flavonoid 7,4′-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts. In: Phytotherapy Research. 2017 ; Vol. 31, No. 3. pp. 449-458.
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