Arborinine

Cytotoxic compounds from the fruits of Uapaca togoensis towards multifactorial drug-resistant cancer cells.[Pubmed:25473921]

Planta Med. 2015 Jan;81(1):32-8.

Cancer cells may rapidly acquire multidrug resistance, mainly due to the presence of adenosine triphosphate-binding cassette transporters, epidermal growth factor receptor, or mutations in the p53 tumor suppressor gene. This work was designed to assess the cytotoxicity of the methanol crude extracts and compounds from the fruits of Uapaca togoensis, namely, beta-amyryl acetate (1), 11-oxo-alpha-amyryl acetate (2), lupeol (3), pomolic acid (4), futokadsurin B (5), arborinin (6), and 3-O-beta-D-glucopyranosyl sitosterol (7) against nine drug sensitive and multidrug-resistant cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of the fruits of U. togoensis and compounds, whilst the caspase-Glo assay was used to detect the activation of caspase enzymes by the fruits of U. togoensis and compound 6. Cell cycle, mitochondrial membrane potential, and levels of reactive oxygen species were all analyzed via flow cytometry. The acridone alkoid 6 and the crude extract from the fruits of U. togoensis were active on all of the nine tested cancer lines with IC50 values below 32 microM and 30 microg/mL, respectively. Compounds 2 and 5 showed selective activities and IC50 values below 99 microM or 42 microM, respectively, which were obtained towards 3/9 and 6/9 tested cancer cell lines. Compound 6 displayed IC50 values below 10 microM towards seven of the nine tested cancer cell lines. The IC50 values ranged from 3.55 microM (against CEM/ADR5000 cells) to 31.77 microM (against CCRF-CEM cells) for alkaloid 6 and from 0.20 microM (against CCRF-CEM cells) to 195.12 microM (against CEM/ADR5000 cells) for doxorubicin. The crude extract of the fruits of U. togoensis induced apoptosis in the CCRF-CEM leukemia cells, which was mediated by the disruption of the mitochondrial membrane potential. Compound 6 also strongly induced apoptosis in CCRF-CEM cells and cell cycle arrest in the G0/G1 and S phases. The crude extract from the fruits of this plant as well as aborinin are potential antiproliferative natural products that deserve further investigation to develop novel cytotoxic drugs to fight sensitive and otherwise drug-resistant phenotypes.

Antifeedant constituents from Fagara macrophylla.[Pubmed:11429249]

Fitoterapia. 2001 Jun;72(5):538-43.

Analysis of the polar fractions of an EtOH extract obtained from the bark of the African medicinal plant Fagara macrophylla led to the isolation and identification of the alkaloids oblongine (6), tembetarine (7) and magnoflorine (8) and the flavonoid hesperidin (9). These compounds, together with other metabolites (1--5) previously isolated from F. macrophylla, were tested for antifeedant activity in a binary-choice bioassay. The acridone alkaloid xanthoxoline (4) was found to have a potent antifeedant activity against larvae of both Spodoptera frugiperda and S. littoralis. 1-Hydroxy-3-methoxy-N-methyl-acridone (2), Arborinine (3), tembetarine (7) and magnoflorine (8) were antifeedant against S. frugiperda.

Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves.[Pubmed:25454460]

Fitoterapia. 2014 Dec;99:276-83.

Hepatitis C virus (HCV) infection is highly prevalent among global populations, with an estimated number of infected patients being 170 million. Approximately 70-80% of patients acutely infected with HCV will progress to chronic liver disease, such as liver cirrhosis and hepatocellular carcinoma, which is a substantial cause of morbidity and mortality worldwide. New therapies for HCV infection have been developed, however, the therapeutic efficacies still need to be improved. Medicinal plants are promising sources for antivirals against HCV. A variety of plants have been tested and proven to be beneficial as antiviral drug candidates against HCV. In this study, we examined extracts, their subfractions and isolated compounds of Ruta angustifolia leaves for antiviral activities against HCV in cell culture. We isolated six compounds, chalepin, scopoletin, gamma-fagarine, Arborinine, kokusaginine and pseudane IX. Among them, chalepin and pseudane IX showed strong anti-HCV activities with 50% inhibitory concentration (IC(5)(0)) of 1.7 +/- 0.5 and 1.4 +/- 0.2 mug/ml, respectively, without apparent cytotoxicity. Their anti-HCV activities were stronger than that of ribavirin (2.8 +/- 0.4 mug/ml), which has been widely used for the treatment of HCV infection. Mode-of-action analyses revealed that chalepin and pseudane IX inhibited HCV at the post-entry step and decreased the levels of HCV RNA replication and viral protein synthesis. We also observed that Arborinine, kokusaginine and gamma-fagarine possessed moderate levels of anti-HCV activities with IC(5)(0) values being 6.4 +/- 0.7, 6.4 +/- 1.6 and 20.4 +/- 0.4 mug/ml, respectively, whereas scopoletin did not exert significant anti-HCV activities at 30 mug/ml.

Antibacterial activity and cytotoxicity of extractives from Ravenia spectabilis.[Pubmed:15261391]

Fitoterapia. 2004 Jul;75(5):510-3.

A methanolic extract of Ravenia spectabilis, an isolated alkaloid, Arborinine plus a fraction comprising Arborinine and gamma-fagarine (VLC), showed mild to significant in vitro antibacterial activity. In a brine shrimp lethality bioassay, the extract and the fraction were found to exhibit moderate cytotoxicity having LC50 of 76.26 microg/ml and 14.98 microg/ml, respectively.