| Kinase Assay: |
| Eur J Cancer Prev. 2015 Jun 5. | | Apoptosis induced by farrerol in human gastric cancer SGC-7901 cells through the mitochondrial-mediated pathway.[Pubmed: 26061993] | Farrerol, a typical flavanone isolated from the Chinese medicinal plant Rhododendron dauricum L., has been found to show various biological activities. However, to the best of our knowledge, its inhibitory actions against cancer cells have not been reported as yet.
METHODS AND RESULTS:
Therefore, the present study aimed to investigate the cytotoxic and apoptotic effects of Farrerol on human gastric cancer SGC-7901 cells. Farrerol showed a 50% inhibition of SGC-7901 cell growth at a concentration of 40.4 μmol/l for 24 h according to MTT assays. The cell morphology results indicated that SGC-7901 cells treated with Farrerol showed several features of apoptotic cell death, which was also confirmed by the Annexin-V FITC/PI double-staining assay. Further studies showed that Farrerol treatment induced the attenuation of mitochondrial membrane potential, accompanied by the release of Cyt-c and the activation of caspase-9 and caspase-3. Furthermore, Farrerol decreased the gene expression of Bcl-2, whereas the gene expression level of Bax was found to increase after Farrerol treatment.
CONCLUSIONS:
These combined results indicated that Farrerol can induce apoptosis through a mitochondrial-mediated pathway. | | Eur J Pharmacol. 2014 Jul 5;734:9-14. | | Farrerol regulates occludin expression in hydrogen peroxide-induced EA.hy926 cells by modulating ERK1/2 activity.[Pubmed: 24726849] | Endothelial tight junction is a crucial intracellular junctional structure that controls paracellular permeability across vascular endothelium. Oxidative stress-mediated elevation in endothelial permeability is associated with pathogenesis of several cardiovascular diseases.
METHODS AND RESULTS:
In the present research, the regulation of Farrerol on occludin, a transmembrane proteins associated with endothelial tight junction, was investigated in hydrogen peroxide-induced human endothelium-derived EA.hy926 cells. Western blot analysis demonstrated that H2O2 exposure caused a significant decrease in occludin expression, but had little effect on ZO-1 expression, and the decrease of occludin expression was significantly attenuated by Farrerol in a dose-dependent manner. Meanwhile, immunofluorescent staining assay also demonstrated that the loss of occludin expression induced by H2O2 exposure was restored by Farrerol pretreatment. Further investigations showed that Farrerol prevented H2O2-induced activation of extracellular signal-regulated kinase (ERK) 1/2 in a dose-dependent manner. The use of U0126, a specific inhibitor of MEK1/2, proved that H2O2-induced decrease of occludin in EA.hy926 cells was likely associated with activation of ERK1/2, which indicated that the regulation of Farrerol on occludin expression in H2O2-induced EA.hy926 cells was likely related to the modulation of ERK1/2 activation.
CONCLUSIONS:
In conclusion, the present study demonstrates for the first time that Farrerol has potential effects on oxidative stress-induced endothelial tight junction disruption and suggests that Farrerol is a potential candidate for the intervention of endothelial permeability-associated cardiovascular diseases. |
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| Cell Research: |
| Can J Physiol Pharmacol. 2013 Sep;91(9):733-40. | | Protective effects of farrerol against hydrogen-peroxide-induced apoptosis in human endothelium-derived EA.hy926 cells.[Pubmed: 23984825] | Vascular endothelium plays an important role in the physiological homeostasis of blood vessels. Endothelial injury is considered to be implicated in the pathogenesis of many cardiovascular diseases, including atherosclerosis. Farrerol, a flavonoid considered to be the major bioactive component in a traditional Chinese herb, "Man-shan-hong", which is the dried leaves of Rhododendron dauricum L., displays many bioactive properties, including antibechic, antibacterial, anti-inflammatory, and the inhibition of vascular smooth muscle cell (VSMC) proliferation.
METHODS AND RESULTS:
In this study, the protective effects of Farrerol on hydrogen peroxide (H2O2)-induced apoptosis in human endothelium-derived EA.hy926 cells were investigated. The results showed that Farrerol significantly inhibited the loss of cell viability and enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in H2O2-induced EA.hy926 cells. Meanwhile, Farrerol inhibited H2O2-induced elevation in the levels of intracellular malondialdehyde and reactive oxygen species, as well as cell apoptosis. Furthermore, real time RT-PCR and Western blot analysis showed that Farrerol significantly decreased the expression of Bax mRNA, Bax, cleaved caspase-3, and phosph-p38 MAPK, while increasing the exporession of Bcl-2 mRNA and Bcl-2 in H2O2-induced EA.hy926 cells.
CONCLUSIONS:
These results are the first demonstration that Farrerol has protective effects against H2O2-induced apoptosis in EA.hy926 cells, and suggests that Farrerol is a potential candidate for the intervention of endothelial-injury-associated cardiovascular diseases. | | Phytomedicine. 2016 Jun 15;23(7):686-93. | | Farrerol inhibited angiogenesis through Akt/mTOR, Erk and Jak2/Stat3 signal pathway.[Pubmed: 27235707] | Farrerol is one of traditional Chinese medicines, isolated from Rhododendron dauricum L. It has been reported that Farrerol exerts multiple biological activities. Angiogenesis is an important drug target for cancer and inflammation therapy, the effect of Farrerol on angiogenesis is unknown.
We aimed to investigate whether Farrerol may have inhibitory effects against angiogenesis.
METHODS AND RESULTS:
Two kinds of endothelial cells, named human umbilical vein endothelia cell and human micro vessel endothelial cells, were used to examine the effect and mechanism of Farrerol on angiogenesis. MTT assay was used to detect cell proliferation, wound healing assay and boyden's chamber assay were used to examine cell migration, Matrigel was used as basement membrane substratum in tube formation assay, Annexin V-FITC/PI dual staining assay and trypan blue staining were used to detect cell apoptosis, mouse aortic rings assay was performed as ex vivo assay, the expression of proteins involved in angiogenesis was tested using western blot, the binding of Farrerol to Stat3 was monitored by docking assay, molecular dynamics simulations and MM-GBSA method.
Farrerol showed an inhibitory effect on proliferation, migration and tube formation of human umbilical vein endothelia cell and human micro vessel endothelial cells in a concentration-dependent manner. Farrerol induced cell cycle arrest and increased the apoptotic percentage of endothelial cells. Farrerol also suppressed the formation of new micro vessels from mouse aortic rings. Moreover, Farrerol reduced the phosphorylation levels of Erk, Akt, mTOR, Jak2 and Stat3 as well as protein expression of Bcl-2 and Bcl-xl. Docking assay, molecular dynamics simulations and MM-GBSA method showed that Farrerol bound to domain of Stat3, Ser613,Gln635, Glu638 and Thr714 are the main residues in Farrerol binding sites with the binding free energy -7.3 ～ -9.0kcal/mol.
CONCLUSIONS:
In this study, we demonstrated that Farrerol inhibited angiogenesis through down regulation of Akt/mTOR, Erk and Jak2/Stat3 signal pathway. The inhibitory effect of Farrerol on angiogenesis suggested that this compound may be helpful to the angiogenesis-related diseases treatment, such as cancer and inflammations. |
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