RESUMEN
Erianin (Eri) is the extract of Dendrobium chrysotoxum Lindl. The NLRP3 inflammasome is a multiprotein complex that plays key roles in a wide variety of chronic inflammation-driven human diseases. Nevertheless, little is known about the protection of Eri against NLRP3 inflammasome-related diseases. In this study, we demonstrated that Eri inhibited NLRP3 inflammasome activation in vitro and in vivo. Mechanistically, Eri directly interacted with NLRP3, leading to inhibition of NLRP3 inflammasome assembly. Eri associated with the Walker A motif in the NACHT domain and suppressed NLRP3 ATPase activity. In mouse models, Eri had therapeutic effects on peritonitis, gouty arthritis and type 2 diabetes, via NLRP3. More importantly, Eri was active ex vivo for synovial fluid cells and monocytes from patients with IAV infection and gout. Eri may serve as a potential novel therapeutic compound against NLRP3-driven diseases.
Asunto(s)
Antiinflamatorios/farmacología , Artritis Gotosa/tratamiento farmacológico , Bibencilos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inflamasomas/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Peritonitis/tratamiento farmacológico , Fenol/farmacología , Animales , Artritis Gotosa/genética , Artritis Gotosa/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Perros , Células HEK293 , Humanos , Inflamasomas/genética , Inflamasomas/metabolismo , Células de Riñón Canino Madin Darby , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Peritonitis/genética , Peritonitis/metabolismo , Dominios y Motivos de Interacción de Proteínas , Células THP-1RESUMEN
OBJECTIVES: To investigate the effect of Shenfu Injection (, SFI) on inflammatory factors in patients with acute myocardial infarction complicated by cardiogenic shock (CS) treated with and intra-aortic balloon pump (IABP). METHODS: This study enrolled 60 patients with ST-segment elevation myocardial infarction (STEMI) complicated by CS. Patients underwent IABP and emergency percutaneous coronary intervention (PCI) were randomly divided into two groups by random number table with 30 cases in each group, one given Sfitreatment (100 mL/24 h), one not. The two groups were then compared in a clinical setting for left ventricular function, biochemical indicators and Inflammatory factors, including C-reactive proteins (CRP), interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). Major adverse cardiac and cerebrovascular events (MACCE) events were compared between patients of the two groups both in-hospital and in follow-ups. RESULTS: The IABP support treatment times of patients in the IABP+Sfigroup were signifificantly shorter than the IABP group (52.87±28.84 vs. 87.45±87.31, P=0.047). In the patients of the IABP+Sfigroup, the CRP peak appeared in 24 h after PCI operation. The CRP peak in the patients of the IABP+Sfigroup was signifificantly lower than that in the IABP group (31.27±3.93 vs. 34.62±3.47, P=0.001). The increases in range of TNF-α in the patients of the IABP+Sfigroup were signifificantly lower than those of the IABP group (182.29±22.79 vs. 195.54±12.02, P=0.007). The increases in range of IL-1 in the patients of the IABP+Sfigroup were signifificantly lower than those of the IABP group (214.98±29.22 vs. 228.60±7.03, P=0.019). The amplitude elevated TNF-α 72 h after admission was an independent risk factor of in-hospital MACCE events (OR 0.973, 95% CI 0.890-0.987, P=0.014) in patients with STEMI and CS. CONCLUSION: Patients with STEMI complicated by CS treated by IABP and Sfihad a reduced inflammatory reaction, a reduced dependence of CS on IABP and shortened the course of disease.
Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/tratamiento farmacológico , Inyecciones , Infarto del Miocardio/tratamiento farmacológico , Choque Cardiogénico/complicaciones , Choque Cardiogénico/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Inflamación/sangre , Inflamación/complicaciones , Mediadores de Inflamación/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/sangre , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Resultado del TratamientoRESUMEN
In our studies, micellar electrokinetic capillary chromatography (MEKC) was employed in fingerprint analysis of Cnidium monnieri for the first time. Average chromatography of 10 batches Cnidium monnieri from Jiangsu province, China, which have long been considered as the original and genuine herbal medicine, was first established as the characteristic fingerprint. Within 25 min the major effective components were separated by 18 mM borate, 12 mM phosphate and 50 mM SDS (pH 9.2) containing 20% methanol. The relative standard deviations of migration times and peak areas were less than 5%. As a new approach of fingerprint, MKCE was compared to the conventional approach-HPLC in our experiments. The fingerprint developed by HPLC comprised 8 peaks that were collected within 40 min. Relative standard deviation (RSD) values of retention times of corresponding peaks in HPLC analysis were very small (maximum 3% and average 0.9%). In conclusion, each two methods had its advantages and disadvantages. Furthermore, besides HPLC, MEKC as a feasible method, could be used in the development of fingerprint of Cnidium monnieri.