Cepharanthine

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.

Bioorg Med Chem Lett. 2014 May 1;24(9):2115-7.

Cepharanthine inhibited HIV-1 cell-cell transmission and cell-free infection via modification of cell membrane fluidity.[Pubmed: 24704028]

The anti-HIV-1 activity of Cepharanthine (CEP), a natural product derived from Stephania cepharantha Hayata, was evaluated.
METHODS AND RESULTS:
CEP stabilized plasma membrane fluidity and inhibited HIV-1 envelope-dependent cell-to-cell fusion of HIV-1-infected cells as well as cell-free infection.
CONCLUSIONS:
It is suggested that CEP inhibited the HIV-1 entry process by reducing plasma membrane fluidity, and the plasma membrane is therefore an identical target to prevent viral infection.

Biochem Biophys Res Commun. 2015 May 1;460(2):136-42.

Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells.[Pubmed: 25747710]

Cepharanthine is a medicinal plant-derived natural compound which possesses potent anti-cancer properties. However, there is little report about its effects on lung cancer cells.
METHODS AND RESULTS:
In this study, we investigated the effects of Cepharanthine on the cell viability and apoptosis in human non-small-cell lung cancer H1299 and A549 cells. It was found that Cepharanthine inhibited the growth of H1299 and A549 cells in a dose-dependent manner which was associated with the generation of reactive oxygen species(ROS) and the dissipation of mitochondrial membrane potential (Δψm). These effects were markedly abrogated when cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, indicating that the apoptosis-inducing effect of Cepharanthine in lung cancer cells was mediated by ROS. In addition, Cepharanthine triggered apoptosis in non-small lung cancer cells via the upregulation of Bax, downregulation of Bcl-2 and significant activation of caspase-3 and PARP.
CONCLUSIONS:
These results provide the rationale for further research and preclinical investigation of Cepharanthine's anti-tumor effect against human non-small-cell lung cancer.

AIDS Res Hum Retroviruses. 1998 Sep 20;14(14):1239-45.

Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells.[Pubmed: 9764907]

Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo.
METHODS AND RESULTS:
As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of Cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of Cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation.
CONCLUSIONS:
These results indicate that Cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing Cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, Cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.

Inflammation. 2014 Apr;37(2):331-7.

Cepharanthine attenuates lipopolysaccharide-induced mice mastitis by suppressing the NF-κB signaling pathway.[Pubmed: 24062060]

Cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effects of CEP on a mouse model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms remain to be elucidated.
METHODS AND RESULTS:
The purpose of the present study was to investigate the effects of CEP on LPS-induced mouse mastitis. The mouse model of mastitis was induced by inoculation of LPS through the canals of the mammary gland. CEP was administered intraperitoneally at 1 h before and 12 h after induction of LPS. The results show that CEP significantly attenuates the infiltration of neutrophils, suppresses myeloperoxidase activity, and reduces the levels of TNF-α, IL-1β, and IL-6 in LPS-induced mouse mastitis. Furthermore, CEP inhibited the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα.
CONCLUSIONS:
All the results suggest that CEP exerts potent anti-inflammatory effects on LPS-induced mouse mastitis. Accordingly, CEP might be a potential therapeutic agent for mastitis.