ABSTRACT
The study investigates the mechanism by which Peganum harmala L. (Luotuopeng, LTP) inhibits tube formation in retinal vascular endothelial cells. Tube formation was induced by treatment of retinal vascular endothelial cells with glucose. The cells were divided into a normal group, model group, and an LTP group. The total length of tube formation was measured. The active components, targets, and pathway by which LTP acts in the treatment of diabetic retinopathy was explored by network pharmacology. The mRNA expression levels of targets [extracellular signal-regulated kinase 2 (ERK2), phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), serine/threonine-protein kinase 1 (AKT1)] related to the mitogen-activated protein kinase (MAPK) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway was measured by real-time PCR. The results of tube formation indicated that compared with the normal group, the total tube length increased in the model group (P < 0.01); after the treatment with LTP, the total tube length decreased compared with the model group (P < 0.01). Network pharmacology revealed that the targets of LTP included PIK3CA, AKT1, and ERK2, and the pathways involved the MAPK signaling pathway and the VEGF signaling pathway. Real-time PCR indicated that compared with the normal group, the mRNA expression levels of ERK2, PIK3CA and AKT1 were elevated in the model group (P < 0.05); after treatment with LTP, the mRNA expression levels of ERK2, PIK3CA and AKT1 decreased compared with the model group (P < 0.05). LTP may inhibit retinal vascular endothelial cell tube formation by regulating the MAPK signaling pathway and the VEGF signaling pathway. This study confirms the multi-targets and multi-pathways of LTP and provides a basis for its use in the treatment of diabetic retinopathy．
ABSTRACT
Objective To investigate the therapeutic effects of oleanolic acid-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS ) nanoparticles (OPTN ) combined with heparin sodium-loaded PLGA-TPGS nanoparticles (HPTN)on liver cancer,and explore whether OPTN combined with HPTN has a synergistic effect by comparing the results of single medication.Methods Coumarin 6 and eosin were used as fluorescent probes to examine the cellular uptake by human liver cancer HepG2 cell and murine ascitic hepatocarcinoma cell strain with high metastasis potential in the lymphatic system (HCa-F).The in vitro cytotoxic combination effect and apoptosis of HepG2 cells induced by OPTN combined with HPTN were also determined using WST-1 assay and Annexin V-FITC staining. The antitumor effect in vivo was determined by tumor growth inhibition rate and hematoxylin & eosin staining (H & E)method.Results Both OPTN with green fluorescence and HPTN with red fluorescence were found in HepG2 cells and HCa-F cells,suggesting that they had been internalized.The cell cytotoxicity test and Annexin V-FITC staining results showed that OPTN combined with HPTN had a synergistic effect.The therapeutic effect in vivo showed that OPTN combined with HPTN effectively inhibited tumor growth better than the drug alone.Conclusion OPTN combined with HPTN has a synergistic effect in more effectively inhibiting liver cancer better than single medication.
ABSTRACT
Objective To investigate the therapeutic effects of oleanolic acid-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS ) nanoparticles (OPTN ) combined with heparin sodium-loaded PLGA-TPGS nanoparticles (HPTN)on liver cancer,and explore whether OPTN combined with HPTN has a synergistic effect by comparing the results of single medication.Methods Coumarin 6 and eosin were used as fluorescent probes to examine the cellular uptake by human liver cancer HepG2 cell and murine ascitic hepatocarcinoma cell strain with high metastasis potential in the lymphatic system (HCa-F).The in vitro cytotoxic combination effect and apoptosis of HepG2 cells induced by OPTN combined with HPTN were also determined using WST-1 assay and Annexin V-FITC staining. The antitumor effect in vivo was determined by tumor growth inhibition rate and hematoxylin & eosin staining (H & E)method.Results Both OPTN with green fluorescence and HPTN with red fluorescence were found in HepG2 cells and HCa-F cells,suggesting that they had been internalized.The cell cytotoxicity test and Annexin V-FITC staining results showed that OPTN combined with HPTN had a synergistic effect.The therapeutic effect in vivo showed that OPTN combined with HPTN effectively inhibited tumor growth better than the drug alone.Conclusion OPTN combined with HPTN has a synergistic effect in more effectively inhibiting liver cancer better than single medication.