Ginsenoside metabolite compound-K regulates macrophage function through inhibition of β-arrestin2

Rui Wang, Mei Zhang, Shanshan Hu, Kangkang Liu, Yu Tai, Juan Tao, Weijie Zhou, Zongbiao Zhao, Qingtong Wang, Wei Wei

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ginsenoside metabolite compound-K (C–K), which is an active metabolite of ginsenoside in vivo, can produce anti-inflammatory affects by activating glucocorticoid receptors (GRs) to inhibit the expression of β-arrestin2. Studies have shown that C–K can inhibit the function of immune cells including macrophage polarization and phagocytosis. However, the mechanism by which C–K regulates macrophage polarization is currently unclear. Toll-like receptors (TLRs) are the pattern recognition receptors on the membrane of immune cells, with TLR4 being especially important in polarization of macrophages. The Gαi-mediated activation of nuclear factor-κB (NF-κB) by TLR4 promotes inflammation and phagocytosis in macrophages by increasing the proportion of type I phenotypic macrophages (M1). Whether C–K inhibits the signal transduction of TLR4-Gαi-NF-κB and how that effects macrophage polarization regulation in murine models of RA is not reported. The coupling of G proteins with receptors is regulated by β-arrestin2, but it has been unclear whether C–K modulates the TLR4 interaction with G proteins by inhibiting the expression of β-arrestin2. To explore these questions, the collagen-induced arthritis (CIA) mouse model was employed, and mice were treated with C–K (112 mg/kg/day). The results depict that C–K treatment inhibits macrophage phagocytosis and reduces the proportion of M1. C–K decreases the overexpressed β-arrestin2, Gαi, TLR4 and NF-κB in macrophages of CIA mice, while increasing the expression of Gαs. Furthermore, C–K promotes TLR4-Gαs coupling and inhibits TLR4-Gαi coupling through β-arrestin2 regulation in macrophages, leading to a decrease in the proportion of M1 to M2 macrophages and improved outcomes in CIA mice.

Original languageEnglish (US)
Article number108909
JournalBiomedicine and Pharmacotherapy
Volume115
DOIs
StatePublished - Jul 1 2019
Externally publishedYes

Fingerprint

Macrophages
Experimental Arthritis
Phagocytosis
GTP-Binding Proteins
ginsenoside M1
Ginsenosides
Pattern Recognition Receptors
Toll-Like Receptors
Glucocorticoid Receptors
Signal Transduction
Anti-Inflammatory Agents
Cell Membrane
Inflammation

Keywords

  • Collagen-induced arthritis (CIA)
  • Ginsenoside metabolite compound-K(C-K)
  • Macrophage
  • Toll-Like receptor 4 (TLR4)
  • β-arrestin2

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ginsenoside metabolite compound-K regulates macrophage function through inhibition of β-arrestin2. / Wang, Rui; Zhang, Mei; Hu, Shanshan; Liu, Kangkang; Tai, Yu; Tao, Juan; Zhou, Weijie; Zhao, Zongbiao; Wang, Qingtong; Wei, Wei.

In: Biomedicine and Pharmacotherapy, Vol. 115, 108909, 01.07.2019.

Research output: Contribution to journalArticle

Wang, Rui ; Zhang, Mei ; Hu, Shanshan ; Liu, Kangkang ; Tai, Yu ; Tao, Juan ; Zhou, Weijie ; Zhao, Zongbiao ; Wang, Qingtong ; Wei, Wei. / Ginsenoside metabolite compound-K regulates macrophage function through inhibition of β-arrestin2. In: Biomedicine and Pharmacotherapy. 2019 ; Vol. 115.
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abstract = "Ginsenoside metabolite compound-K (C–K), which is an active metabolite of ginsenoside in vivo, can produce anti-inflammatory affects by activating glucocorticoid receptors (GRs) to inhibit the expression of β-arrestin2. Studies have shown that C–K can inhibit the function of immune cells including macrophage polarization and phagocytosis. However, the mechanism by which C–K regulates macrophage polarization is currently unclear. Toll-like receptors (TLRs) are the pattern recognition receptors on the membrane of immune cells, with TLR4 being especially important in polarization of macrophages. The Gαi-mediated activation of nuclear factor-κB (NF-κB) by TLR4 promotes inflammation and phagocytosis in macrophages by increasing the proportion of type I phenotypic macrophages (M1). Whether C–K inhibits the signal transduction of TLR4-Gαi-NF-κB and how that effects macrophage polarization regulation in murine models of RA is not reported. The coupling of G proteins with receptors is regulated by β-arrestin2, but it has been unclear whether C–K modulates the TLR4 interaction with G proteins by inhibiting the expression of β-arrestin2. To explore these questions, the collagen-induced arthritis (CIA) mouse model was employed, and mice were treated with C–K (112 mg/kg/day). The results depict that C–K treatment inhibits macrophage phagocytosis and reduces the proportion of M1. C–K decreases the overexpressed β-arrestin2, Gαi, TLR4 and NF-κB in macrophages of CIA mice, while increasing the expression of Gαs. Furthermore, C–K promotes TLR4-Gαs coupling and inhibits TLR4-Gαi coupling through β-arrestin2 regulation in macrophages, leading to a decrease in the proportion of M1 to M2 macrophages and improved outcomes in CIA mice.",
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AU - Tao, Juan

AU - Zhou, Weijie

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