| In vitro: |
| J Pharmacol Sci. 2014;125(1):74-82. Epub 2014 Apr 24. | | Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells.[Pubmed: 24758922] | Autophagy is a highly regulated and multi-step biological process that serves to remove damaged cytoplasmic components and organelles. It has been suggested that the activation of autophagy may be a promising therapeutic strategy for cancer treatment by triggering cell death.
METHODS AND RESULTS:
In this study, we reported that cyclovirobuxine D (CVB-D), an alkaloid component in a traditional Chinese herb, could induce autophagy in the MCF-7 human breast cancer cell line. CVB-D inhibited the viability of MCF-7 cells in a concentration- and time-dependent manner. Activation of autophagy was characterized by transmission electron microscopy, monodansylcadaverine staining, and expression of autophagy marker microtubule-associated protein 1 light chain 3 (LC3). After CVB-D treatment, a clear accumulation of autophagosomes was observed accompanied with elevated LC3 fluorescent puncta. Western blot analysis revealed that CVB-D significantly promoted the conversion from LC3-I to LC3-II and the expression of autophagy-related protein 5 (ATG5), which are both essential for autophagosome formation. On the other hand, CVB-D-induced autophagy and decrease in cell viability could be blocked by 3-methyladenine, a well-established autophagy inhibitor. Moreover, CVB-D attenuated the phosphorylation of Akt and mTOR, two pivotal suppressors in autophagy pathways.
CONCLUSIONS:
These findings shed new light on the pharmacological actions and mechanism of CVB-D and may support the potential utility of autophagy inducers in cancer treatment. | | Chinese Journal of New Drugs, 2012, 21(3):240-5. | | Comparison of the vasorelaxant effects of cyclovirobuxine D and its derivatives in rat aorta rings[Reference: WebLink] | To compare the vasorelaxant effects of cyclovirobuxine D (CVB-D) and its derivatives in isolated rat thoracic aorta rings.
METHODS AND RESULTS:
Effects of CVB-D and its derivatives at various concentrations (from 1×10 -5 to 6×10 -4 mol·L -1) on contraction of aorta rings induced by potassium chloride (KCl) or phenylephrine (PE) were evaluated. Effects of preincubation with CVB-D or CBV-D3 at 6×10 -4 mol·L -1 on KCl- or PE-induced contraction were assessed in the aorta rings. In KCl- or PE-precontracted aorta rings, CVB-D showed a concentration-dependent vasorelaxant effect, CVB-D1 showed a weak vessel relaxation effect, but CVB-D2 showed no effect at concentrations of 1×10 -5~6×10 -4 mol·L -1. CVB-D3 showed a stronger vesorelaxant effect than CVB-D in the rings precontracted by KCl or PE. Furthermore, both CVB-D and CVB-D3 exhibited stronger vasorelaxation effects in the aorta rings with intacted endothelium than in the aorta rings with denuded endothelium. Additionally, preincubation with both CVB-D and CVB-D3 inhibited KCl- or PE-induced contraction, and the inhibitive effect of CVB-D3 was stronger than CVB-D.
CONCLUSIONS:
CVB-D and CVB-D3 have similar vasorelaxant effect, but CVB-D3 owned a higher maximum effect than CVB-D. |
|
| In vivo: |
| Fitoterapia. 2011 Sep;82(6):868-77. | | Beneficial effect of Cyclovirobuxine D on heart failure rats following myocardial infarction.[Pubmed: 21575690] | The effect of Cyclovirobuxine D, an active ingredient from Buxus microphylla, was investigated in the potential prevention of cardiac dysfunction in rats with congestive heart failure.
METHODS AND RESULTS:
Heart failure was induced by left coronary artery occlusion and verified using echocardiography. Cyclovirobuxine D was administered for 30 days (0.5, 1.0 and 2.0mg/kg, ig) and mortality, cardiac function, hemodynamics, microcirculation, histology and ultrastructure assessments were observed.
CONCLUSIONS:
Results from the present study suggest that Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction and supports the potential for Cyclovirobuxine D as a new therapy for heart failure. |
|
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