| Description: |
Cepharanthine has anti-plasmodial, anti-tumor , anti-inflammatory, antiallergic, antioxidant, and immunomodulatory activities in vivo, and it is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Cepharanthine inhibits the HIV-1 entry process by reducing plasma membrane fluidity, and the plasma membrane is therefore an identical target to prevent viral infection.
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| In vitro: |
| Malar J. 2014 Aug 22;13:327. | | In vitro antiplasmodial activity of cepharanthine.[Pubmed: 25145413] | New classes of anti-malarial drugs are needed to control the alarming Plasmodium falciparum resistance toward current anti-malarial therapy. The ethnopharmacological approach allows the discovery of original chemical structures from the vegetable biodiversity. Previous studies led to the selection of a bisbenzylisoquinoline, called cepharanthine and isolated from a Cambodian plant: Stephania rotunda. Cepharanthine could exert a mechanism of action different from commonly used drugs. Potential plasmodial targets are reported here.
METHODS AND RESULTS:
To study the mechanism of action of cepharanthine, a combined approach using phenotypic and transcriptomic techniques was undertaken.
Cepharanthine blocked P. falciparum development in ring stage. On a culture of synchronized ring stage, the comparisons of expression profiles showed that the samples treated with 5 μM of cepharanthine (IC90) were significantly closer to the initial controls than to the final ones. After a two-way ANOVA (p-value < 0.05) on the microarray results, 1,141 probes among 9,722 presented a significant differential expression.A gene ontology analysis showed that the Maurer's clefts seem particularly down-regulated by cepharanthine. The analysis of metabolic pathways showed an impact on cell-cell interactions (cytoadherence and rosetting), glycolysis and isoprenoid pathways. Organellar functions, more particularly constituted by apicoplast and mitochondrion, are targeted too.
CONCLUSIONS:
The blockage at the ring stage by cepharanthine is described for the first time. Transcriptomic approach confirmed that cepharanthine might have a potential innovative antiplasmodial mechanism of action. Thus, cepharanthine might play an ongoing role in the progress on anti-malarial drug discovery efforts. | | J Enzyme Inhib Med Chem. 2010 Feb;25(1):44-53. | | Antioxidant activity of bisbenzylisoquinoline alkaloids from Stephania rotunda: cepharanthine and fangchinoline.[Pubmed: 20030508 ] |
METHODS AND RESULTS:
In the present study, we determined the antioxidant activity of cepharanthine and fangchinoline from Stephania rotunda by performing different in vitro antioxidant assays, including 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, N,N- dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging, superoxide anion (O2*-) radical scavenging, hydrogen peroxide scavenging, total antioxidant activity, reducing power, and ferrous ion (Fe2+) chelating activities.
Cepharanthine and fangchinoline showed 94.6 and 93.3% inhibition on lipid peroxidation of linoleic acid emulsion at 30 microg/mL concentration, respectively. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol, and trolox indicated inhibitions of 83.3, 92.2, 72.4, and 81.3% on peroxidation of linoleic acid emulsion at the same concentration (30 microg/mL), respectively.
CONCLUSIONS:
According to the results, cepharanthine and fangchinoline have effective antioxidant and radical scavenging activity. |
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