RESUMO
Conventional treatment methods are not effective enough to fight the rapid increase in cancer cases. The interest is increasing in the investigation of herbal sources for the development of new anticancer therapeutics. This study aims to investigate the antitumor capacity of Hypericum alpestre (H. alpestre) extract in vitro and in vivo, either alone or in combination with the inhibitors of the l-arginine/polyamine/nitric oxide (NO) pathway, and to characterize its active phytochemicals using advanced chromatographic techniques. Our previous reports suggest beneficial effects of the arginase inhibitor NG-hydroxy-nor- l-arginine and NO inhibitor NG-nitro-Larginine methyl ester in the treatment of breast cancer via downregulation of polyamine and NO synthesis. Here, the antitumor properties of H. alpestre and its combinations were explored in vivo, in a rat model of mammary gland carcinogenesis induced by subcutaneous injection of 7,12-dimethylbenz[a]anthracene. The study revealed strong antiradical activity of H. alpestre aerial part extract in chemical (DPPH/ABTS) tests. In the in vitro antioxidant activity test, the H. alpestre extract demonstrated pro-oxidant characteristics in human colorectal (HT29) cells, which were contingent upon the hemostatic condition of the cells. The H. alpestre extract expressed a cytotoxic effect on HT29 and breast cancer (MCF-7) cells measured by the MTT test. According to comet assay results, H. alpestre extract did not exhibit genotoxic activity nor possessed antigenotoxic properties in HT29 cells. Overall, 233 substances have been identified and annotated in H. alpestre extract using the LC-Q-Orbitrap HRMS system. In vivo experiments using rat breast cancer models revealed that the H. alpestre extract activated the antioxidant enzymes in the liver, brain, and tumors. H. alpestre combined with chemotherapeutic agents attenuated cancer-like histological alterations and showed significant reductions in tumor blood vessel area. Thus, either alone or in combination with Nω -OH-nor- l-arginine and Nω -nitro- l-arginine methyl ester, H. alpestre extract exhibits pro- and antioxidant, antiangiogenic, and cytotoxic effects.
Assuntos
Neoplasias da Mama , Hypericum , Humanos , Animais , Ratos , Feminino , Antioxidantes/farmacologia , Arginina , Carcinogênese , Transformação Celular Neoplásica , Redes e Vias Metabólicas , Neoplasias da Mama/tratamento farmacológico , PoliaminasRESUMO
Ligustrum vulgare (LV), widely cultivated in Europe and often used in hedges, has been historically recognized in folk medicine for its potential health benefits. This study focused on exploring the untargeted identification of secondary metabolites in ethanol extracts (70% v/v) from different morphological parts (young shoots, leaves, flowers and fruits) of LV at various stages of plant development, using ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS). Additionally, the selected biological activities (antioxidant activity, cyclooxygenase-2 inhibition (COX-2), α-amylase inhibition and cytotoxicity) of the tested extracts were determined. Untargeted metabolomics showed that LV extracts were a rich source of phenylethanoid compounds, flavonoids, iridoids and their derivatives. The flowers of LV had the highest content of oleuropein (33.43 ± 2.48 mg/g d.w.). The lowest antioxidant activity was obtained for ripe and post-seasonal fruits, while in the case of other samples, the activity was at a similar level. All tested extracts showed α-amylase and COX-2 inhibitory activity. In addition, LV extracts showed strong antiproliferative properties in colorectal (HT29) and liver (HepG2) cancer cell lines. The obtained results show the difference in the content of bioactive compounds in various morphological parts of Ligustrum vulgare. These differences may influence the multifaceted medicinal potential of this plant.