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We have previously shown that six propolins, A-F, could be isolated from Taiwanese propolis (TP) and that they exerted a broad spectrum of biological activities. Recently, we isolated a seventh compound, propolin G. Its chemical structure has been identified by NMR and fast atom bombardment-mass spectrometry spectra and was found to be identical to a known compound, nymphaeol C. We used high-performance liquid chromatography to determine the relative contents of propolins C, D, F, and G in TP collected in various seasons and regions and found them to be relatively higher in TPs collected from May to July than from September to October. In our present study, we were interested in the various biological activities of TP extract as well as in propolin G as a pure compound. We found that propolin G could efficiently induce apoptosis in brain cancer cell lines (glioma and glioblastoma). The apoptosis might have been through a mitochondrial- and caspase-dependent pathway. This result demonstrated that the TP collection season was more an important factor than the geographical region. Propolis has been suggested to possess a potent antioxidant activity. We further evaluated the antioxidant property of propolin G using DPPH (1,2-diphenyl-2-picryhydrazyl). Our results indicate that propolin G does possess free radical scavenging activity. We also evaluated the neuroprotective action of propolin G, TP, and BP (Brazilian propolis) extracts against oxidative stress in rat primary cortical neurons. Our data demonstrate that propolin G and TP extracts have a marked neuroprotective effect that is greater than BP extract. In conclusion, the isolation and characterization of propolin G from TP have demonstrated for the first time that this compound is a potent inducer of apoptosis in brain cancer cells and that this compound and TP extract exhibit a protective effect against oxidative stress in rat cortical neurons.

Propolis, a natural product collected by honeybee, has been reported to exert a wide spectrum of biological functions. In this study, we have isolated a novel component, namely, propolin H, and investigated its effects in human carcinoma cells. Propolin H inhibited the proliferation of human lung carcinoma cell lines in MTT assay, and a significant G1 arrest was observed to occur in a dosedependent manner at 24 h of exposure in H460 cells. After treatment with propolin H in H460 cells, the content of the CDK inhibitor p21 Waf1/Cip1 protein increased in correlation with the elevation in p53 levels. Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showed that propolin H has inhibited CDK2 and CDK4 kinase activities. Accordingly, coimmunoprecipitations revealed an increased association of both CDK2 and CDK4 immunoreactive protein with the p21Waf1/Cip1 protein complex under propolin H-treated conditions. Additionally, we found that propolin H enhanced the expression of p21Waf1/Cip1 in p53-mutant and p53-null lung carcinoma cell lines, following the induction of G1 arrest. Together, these findings suggest that the induction of p21Waf1/Cip1 expression occurred through p53-dependent and -independent pathways in propolin H-treated cells. Propolin H exerts its significantly growth inhibitory effects and may have therapeutic applications.