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  3. The anti-inflammatory effect of ε-viniferin by specifically targeting formyl peptide receptor 1 on human neutrophils

The anti-inflammatory effect of ε-viniferin by specifically targeting formyl peptide receptor 1 on human neutrophils

  • Chem Biol Interact. 2021 Aug 25:345:109490. doi: 10.1016/j.cbi.2021.109490.
Hsiang-Ruei Liao 1,  Chin-Hsuan Lin 2,  Jih-Jung Chen 3,  Fu-Chao Liu 4,  Ching-Ping Tseng 5
Affiliations

Affiliations

  • 1 Graduate Institute of Natural Products, College of Medicine, Chang-Gung University, Tao Yuan, Taiwan, Republic of China; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, 333, Taiwan, Republic of China; Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China. Electronic address: [email protected].
  • 2 Graduate Institute of Natural Products, College of Medicine, Chang-Gung University, Tao Yuan, Taiwan, Republic of China.
  • 3 Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, Republic of China; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, Republic of China.
  • 4 Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China.
  • 5 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, 333, Taiwan, Republic of China; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei Shan, Taoyuan, 333, Taiwan, Republic of China; Molecular Medicine Research Center, Chang Gung University, Kwei Shan, Taoyuan, 333, Taiwan, Republic of China; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Kwei Shan, Taoyuan, 333, Taiwan, Republic of China.
PMID: 34144024 DOI: 10.1016/j.cbi.2021.109490
Abstract

The uncontrol respiratory burst in neutrophils can lead to inflammation and tissue damage. This study investigates the effect and the underlying mechanism of ε-viniferin, a lignan from the root of Vitis thunbergii var. thunbergii, inhibits N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP) induced respiratory burst by antagonizing formyl peptide receptor 1 in human neutrophils. Briefly, ε-viniferin specifically inhibited fMLP (0.1 μM: formyl peptide receptor 1 agonist or 1 μM: formyl peptide receptor 1, 2 agonist)-induced superoxide anion production in a concentration-dependent manner (IC50 = 2.30 ± 0.96 or 9.80 ± 0.21 μM, respectively) without affecting this induced by formyl peptide receptor 2 agonist (WKYMVM). ε-viniferin inhibited fMLP (0.1 μM)-induced phosphorylation of ERK, Akt, Src or intracellular calcium mobilization without affecting these caused by WKYMVM. The synergistic suppression of fMLP (1 μM)-induced superoxide anion production was observed only in the combination of ε-viniferin and formyl peptide receptor 2 antagonist (WRW4) but not in combination of ε-viniferin and formyl peptide receptor 1 antagonist (cyclosporine H). ε-viniferin inhibited FITC-fMLP binding to formyl peptide receptors. Moreover, the synergistic suppression of FITC-fMLP binding was observation only in the combination of ε-viniferin and WRW4 but not in other combinations. ATPγS induced superoxide anion production through formyl peptide receptor 1 in fMLP desensitized neutrophils and this effect was inhibited by ε-viniferin. The concentration-response curve of fMLP-induced superoxide anion was not parallel shifted by ε-viniferin. Furthermore, the inhibiting effect of ε-viniferin on fMLP-induced superoxide anion production was reversible. These results suggest that ε-viniferin is an antagonist of formyl peptide receptor 1 in a reversible and non-competitive manner.

Keywords

Formyl-peptide receptors; Neutrophil; Vitis thunbergii var. thunbergii; fMLP; ε-viniferin.

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