RESUMEN
Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 µg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1ß content compared with control group. 250 µg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.
Asunto(s)
Antivirales , Simulación del Acoplamiento Molecular , Polisacáridos , Virus de la Gastroenteritis Transmisible , Animales , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Células RAW 264.7 , Virus de la Gastroenteritis Transmisible/efectos de los fármacos , Antivirales/farmacología , Rizoma/química , Interleucina-1beta/metabolismo , Peso Molecular , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Línea Celular , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Espectroscopía Infrarroja por Transformada de Fourier , Monosacáridos , Óxido Nítrico/metabolismo , Factores Inmunológicos/farmacologíaRESUMEN
Pulmonary hypertension (PH) is a fatal disease with no existing curative drugs. NF-E2-related factor 2 (NRF2) a pivotal molecular in cellular protection, was investigated in PH models to elucidate its role in regulating abnormal phenotypes in pulmonary artery cells. We examined the expression of NRF2 in PH models and explored the role of NRF2 in regulating abnormal phenotypes in pulmonary artery cells. We determined the expression level of NRF2 in lung tissues of PH model decreased significantly. We found that NRF2 was reduced in rat pulmonary artery endothelial cells (rPAEC) under hypoxia, while it was overexpressed in rat pulmonary artery smooth muscle cells (rPASMC) under hypoxia. Next, the results showed that knockdown NRF2 in rPAEC promoted endothelial-mesenchymal transformation and upregulated reactive oxygen species level. After the rPASMC was treated with siRNA or activator, we found that NRF2 could accelerate cell migration by affecting MMP2/3/7, and promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/P70S6K pathways. Therefore, the study has shown that the clinical application of NRF2 activator in the treatment of pulmonary hypertension may cause side effects of promoting the proliferation and migration of rPASMC. Attention should be paid to the combination of NRF2 activators.
Asunto(s)
Movimiento Celular , Proliferación Celular , Hipertensión Pulmonar , Factor 2 Relacionado con NF-E2 , Arteria Pulmonar , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Animales , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Ratas , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Miocitos del Músculo Liso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Masculino , Transducción de Señal , Transición Epitelial-Mesenquimal/genética , Ratas Sprague-Dawley , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: This review highlights the current knowledge of polysaccharide from Lilii Bulbus, including the extraction, purification, structure, structure modification , biological activities and application, which will hopefully provide reference for further research and development of polysaccharide from Lilii Bulbus. MATERIALS AND METHODS: Literature searches were conducted on the following databases: Pubmed, ACS website, Elsevier, Google Scholar, Web of Science and CNKI database. Keywords such as "Lilii Bulbus", "polysaccharide", "preparation", "biological activities" and "application" were used to search relevant journals and contents, and some irrelevant contents were excluded. RESULTS: In general, the study of Lilium Bulbus polysaccharide extraction and purification, structure characterization and biological activity has made substantial progress, these findings highlight the lilium brownii polysaccharide enormous potential in biomedical applications, of lilium brownii polysaccharide laid a solid foundation for further research. DISCUSSION AND CONCLUSIONS: However, it should be noted that the relevant mechanism of the effective effect of lily bulb polysaccharide still needs to be worked on by researchers. These findings highlight the great potential of lily polysaccharides in biomedical applications, and lay a solid foundation for further research on lily polysaccharides.