Emodin inhibits ATP-induced IL-1β secretion, ROS production and phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X₇ receptor.

Abstract:

CONTEXT:Previous in vitro studies have demonstrated that emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from the rhizome of Rheum palmatum L., can inhibit the activation of P2X₇ receptors (P2X₇R) as a potential antagonist. However, the effects of emodin on P2X₇R-related inflammatory processes remain unclear. OBJECTIVE:This study aimed to investigate the effects of emodin on different inflammation responses of macrophages induced by ATP, the natural ligand of P2X₇R. MATERIALS AND METHODS:Rat peritoneal macrophages were treated with millimolar ATP and emodin (0.1, 0.3, 1, 3, 10 µM) or brilliant blue G (BBG, 0.1, 1, 10 µM). Cytosolic Ca²⁺ concentration ([Ca²⁺]c) was detected by fluorescent Ca²⁺ imaging. Interleukin-1β (IL-1β) release was measured by rat IL-1β ELISA kits. Reactive oxygen species (ROS) generation was examined by dihydroethidium (DHE) fluorescent staining. Phagocytic activity was tested by neutral red uptake assay. RESULTS:We found that the [Ca²⁺](c) increase evoked by ATP (5 mM) was inhibited by emodin, in a dose-dependent manner with IC₅₀ of 0.5 μM. Furthermore, emodin reduced the IL-1β release induced by ATP (2 mM) in lipopolysaccharide (LPS)-activated macrophages, with an IC₅₀ of 1.6 μM. Emodin also strongly suppressed the ROS production and phagocytosis attenuation triggered by ATP (1 mM), with IC₅₀ values of 1 μM and 0.7 μM, respectively. Besides, BBG, a specific antagonist of P2X₇R, exhibited similar suppressive effects on these inflammation responses. CONCLUSION:These results showed the inhibitory effects of emodin on ATP-induced [Ca²⁺](c) increase, IL-1β release, ROS production and phagocytosis attenuation in rat peritoneal macrophages, by inhibiting the activation of P2X₇R.

journal_name

Pharm Biol

journal_title

Pharmaceutical biology

authors

Zhu S,Wang Y,Wang X,Li J,Hu F

doi

10.3109/13880209.2013.810648

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

51-7

issue

1

eissn

1388-0209

issn

1744-5116

journal_volume

52

pub_type

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