| Description: |
Dihydrosanguinarine has antifungal and anticancer activity.Dihydrosanguinarine at concentrations from 5 microM induced primarily necrosis, whereas apoptosis occurred at 10 microM and above. Dihydrosanguinarine has potential application in the therapy of serious infection caused by I. multifiliis. |
| Targets: |
P450 (e.g. CYP17) | Caspase |
| In vitro: |
| Toxicol In Vitro. 2009 Jun;23(4):580-8. | | Cytotoxic activity of sanguinarine and dihydrosanguinarine in human promyelocytic leukemia HL-60 cells.[Pubmed: 19346183] | The benzo[c]phenanthridine alkaloid sanguinarine has been studied for its antiproliferative activity in many cell types. Almost nothing however, is known about the cytotoxic effects of dihydrosanguinarine, a metabolite of sanguinarine.
METHODS AND RESULTS:
We compared the cytotoxicity of sanguinarine and dihydrosanguinarine in human leukemia HL-60 cells. Sanguinarine produced a dose-dependent decline in cell viability with IC(50) (inhibitor concentration required for 50% inhibition of cell viability) of 0.9 microM as determined by MTT assay after 4h exposure. Dihydrosanguinarine showed much less cytotoxicity than sanguinarine: at the highest concentration tested (20 microM) and 24h exposure, dihydrosanguinarine decreased viability only to 52%. Cytotoxic effects of both alkaloids were accompanied by activation of the intrinsic apoptotic pathway since we observed the dissipation of mitochondrial membrane potential, induction of caspase-9 and -3 activities, the appearance of sub-G(1) DNA and loss of plasma membrane asymmetry. This aside, sanguinarine also increased the activity of caspase-8. As shown by flow cytometry using annexin V/propidium iodide staining, 0.5 microM sanguinarine induced apoptosis while 1-4 microM sanguinarine caused necrotic cell death. In contrast, dihydrosanguinarine at concentrations from 5 microM induced primarily necrosis, whereas apoptosis occurred at 10 microM and above.
CONCLUSIONS:
We conclude that both alkaloids may cause, depending on the alkaloid concentration, both necrosis and apoptosis of HL-60 cells. |
|
| In vivo: |
| Vet Parasitol. 2011 Dec 29;183(1-2):8-13. | | Antiparasitic efficacy of dihydrosanguinarine and dihydrochelerythrine from Macleaya microcarpa against Ichthyophthirius multifiliis in richadsin (Squaliobarbus curriculus).[Pubmed: 21813242] | Ichthyophthirius multifiliis is a holotrichous protozoan that invades the gills and skin surfaces of fish and can cause morbidity and high mortality in most species of freshwater fish worldwide. The present study was undertaken to investigate the antiparasitic activity of crude extracts and pure compounds from the leaves of Macleaya microcarpa.
METHODS AND RESULTS:
The chloroform extract showed a promising antiparasitic activity against I. multifiliis. Based on these finding, the chloroform extract was fractionated on silica gel column chromatography in a bioactivity-guided isolation affording two compounds showing potent activity. The structures of the two compounds were elucidated as dihydrosanguinarine and dihydrochelerythrine by hydrogen and carbon-13 nuclear magnetic resonance spectrum and electron ionization mass spectrometry. The in vivo tests revealed that dihydrosanguinarine and dihydrochelerythrine were effective against I. multifiliis with median effective concentration (EC(50)) values of 5.18 and 9.43 mg/l, respectively. The acute toxicities (LC(50)) of dihydrosanguinarine and dihydrochelerythrine for richadsin were 13.3 and 18.2mg/l, respectively.
CONCLUSIONS:
The overall results provided important information for the potential application of dihydrosanguinarine and dihydrochelerythrine in the therapy of serious infection caused by I. multifiliis. |
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