RESUMEN
Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.
Asunto(s)
Anemarrhena/química , Antiinflamatorios/farmacología , Cardiotónicos/farmacología , Saponinas/farmacología , Esteroides/farmacología , Animales , Animales Modificados Genéticamente , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Cardiotónicos/aislamiento & purificación , Cardiotónicos/toxicidad , Femenino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Rizoma , Saponinas/aislamiento & purificación , Saponinas/toxicidad , Esteroides/aislamiento & purificación , Esteroides/toxicidad , Pez CebraRESUMEN
Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on traditional Chinese medicine. Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis. As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. Fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkage t", variable importance in projection and partial least-squares discriminant analysis. N-Acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies.
Asunto(s)
Antipiréticos/farmacocinética , Biomarcadores/orina , Medicamentos Herbarios Chinos/farmacocinética , Metaboloma/efectos de los fármacos , Metabolómica/métodos , Animales , Antipiréticos/farmacología , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Femenino , Fiebre/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The ginsenoside Rg1 is the most abundant compound in ginseng. Recent studies showed that Rg1 had neuroprotective effects on neuronal cells. The present study was to prepare Rg1-loaded alginate-chitosan microspheres and research the effects of microspheres on human bone marrow (BM) stromal cells (hBMSC). The alginate-chitosan microspheres were prepared by mechanical emulsification technique in combination with ion (Ca2+) and chitosan solidification. Subsequently, the microspheres were employed to load Rg1 ginseng extracts. The microspheres had a smooth surface and were spherical in shape. The average diameter of the microspheres was 3.95 µm. The loading efficiency was approximately 2.12%. The purity of isolated hBMSC was over 98.8%. Rg1-loaded microspheres could promote hBMSC proliferation and differentiation. Meanwhile, Rg1-loaded microspheres could also suppress hBMSC apoptosis induced by hypoxia-reoxygenation. In conclusion, these loaded microspheres may be used in the research of neuroprotective effects of Rg1.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Ginsenósidos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Alginatos/química , Células Cultivadas , Quitosano/química , Portadores de Fármacos/química , Medicamentos Herbarios Chinos/administración & dosificación , Ginsenósidos/administración & dosificación , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Células Madre Mesenquimatosas/citología , Fármacos Neuroprotectores/administración & dosificación , Tamaño de la PartículaRESUMEN
In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information about xyloketal A as a SOCE inhibitor for further evaluation.