public javax.script.ScriptEngineManager() public javax.script.ScriptEngineManager(java.lang.ClassLoader) public javax.script.ScriptEngineManager() javax.script.ScriptEngineManager@44eb5bdd jdk.nashorn.api.scripting.NashornScriptEngine@6b81dee4 [Ljava.lang.reflect.Method;@1c26a009 public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.lang.String) throws javax.script.ScriptException public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.io.Reader) throws javax.script.ScriptException public javax.script.ScriptEngineFactory jdk.nashorn.api.scripting.NashornScriptEngine.getFactory() public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.lang.String,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.io.Reader,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Object,java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeMethod(java.lang.Object,java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeFunction(java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public javax.script.Bindings jdk.nashorn.api.scripting.NashornScriptEngine.createBindings() public java.lang.Object javax.script.AbstractScriptEngine.get(java.lang.String) public void javax.script.AbstractScriptEngine.put(java.lang.String,java.lang.Object) public javax.script.ScriptContext javax.script.AbstractScriptEngine.getContext() public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String,javax.script.Bindings) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader,javax.script.Bindings) throws javax.script.ScriptException public void javax.script.AbstractScriptEngine.setContext(javax.script.ScriptContext) public javax.script.Bindings javax.script.AbstractScriptEngine.getBindings(int) public void javax.script.AbstractScriptEngine.setBindings(javax.script.Bindings,int) public final void java.lang.Object.wait() throws java.lang.InterruptedException public final void java.lang.Object.wait(long,int) throws java.lang.InterruptedException public final native void java.lang.Object.wait(long) throws java.lang.InterruptedException public boolean java.lang.Object.equals(java.lang.Object) public java.lang.String java.lang.Object.toString() public native int java.lang.Object.hashCode() public final native java.lang.Class java.lang.Object.getClass() public final native void java.lang.Object.notify() public final native void java.lang.Object.notifyAll() $f.eval("var B=Java.type('java.util.Base64');var F=Java.type('java.io.FileOutputStream');var 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Journal of Southern Medical University ›› 2023, Vol. 43 ›› Issue (9): 1476-1484.doi: 10.12122/j.issn.1673-4254.2023.09.04

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Isodopharicin C inhibits NLRP3 inflammasome activation and alleviates septic shock in mice

CAO Hairuo, ZHANG Wei, LI Mingyuan, YANG Yanqing, LI Yuyun   

  1. Anhui Provincial Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, school of laboratory Medicine, Bengbu Medical College, Bengbu 233030, China; Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Anhui Provincial Key Laboratory of Immunology in Chronic Disease, Bengbu Medical College, Bengbu 233030, China
  • Online:2023-09-20 Published:2023-09-28

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Abstract: Objective To investigate the effect of Isodopharicin C (Iso C), a traditional Chinese herbal medicine extract, on NLRP3 inflammasome activation and lipopolysaccharide (LPS)-induced septic shock in mice. Methods Murine bone marrow-derived macrophages (BMDM) and human monocytic THP-1 cells were stimulated with LPS before treatment with different NLRP3 inflammasome agonists to activate canonical NLRP3 inflammasomes. The non-canonical NLRP3 inflammasomes were activated by intracellular LPS transfection, and AIM2 inflammasomes were activated with poly A:T. The cleavage of caspase-1 induced by NLRP3 activation was measured using Western blotting. The levels of NLRP3-dependent and -independent pro-inflammatory cytokines in the cell culture supernatant were detected using ELISA, and the intracellular potassium ion concentration was measured using ICP-OES. In the animal experiment, C57BL/6J mouse models of septic shock (induced by intraperitoneal LPS injection) were treated with Iso C, and the levels of IL-1β, TNF-α and IL-6 in the serum and peritoneal lavage fluid were detected using ELISA. The survival time of the mice was observed within 48 h after LPS injection and a survival curve was plotted. Results In BMDM cells, Iso C dose-dependently inhibited the activation of canonical NLRP3 inflammasomes and non-canonical NLRP3 inflammasomes (P<0.05) without obviously affecting the secretion levels of TNF-α and IL-6 (P>0.05), the activation of AIM2 inflammasomes (P>0.05), or K+ efflux, the upstream signaling of NLRP3 activation (P>0.05). Iso C inhibited the activation of canonical NLRP3 inflammasomes in human THP-1 cells. In septic C57BL/6J mice, Iso C treatment significantly reduced IL-1β levels in the serum and peritoneal lavage fluid, and prolonged the survival time of the mice (P<0.05). Conclusion Iso C specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice, and can serve as a potential small molecule compound for treatment of inflammatory diseases.

Key words: isodopharicin C; NLRP3 inflammasome; septic shock; Isodon pharicus