Hypericum alpestre extract exhibits in vitro and in vivo anticancer properties by regulating the cellular antioxidant system and metabolic pathway of L‐arginine

Abstract

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.

Impact of Immobilization Stress on Erythropoiesis, Alterations in the Antioxidant System, and Potential Correction with Stevia rebaudiana Bertoni in Rabbit

“…Catalase activity was determined by the μmol of hydrogen peroxide broken down in 1 mg of protein. Peroxidase activity was determined according to the spectroscopic method [24], and the activity of peroxidase is expressed in μmol of hydrogen peroxide/ min/mg protein.…”

Royal Jelly-Mediated Silver Nanoparticles Show Promising Anti-Cancer Effect on HeLa and A549 Cells Through Modulation of the VEGFa/PI3K/Akt/MMP-2 Pathway

“…After incubation, the medium was removed, and the cells were treated with DMSO to dissolve the formed formazan crystals. Optical density was then measured at a wavelength of 570nm using a SPECTROstar® Nano (Ginovyan et al, 2024). 2 6.Cell staining with hematoxylin and eosin They were stained with hematoxylin and eosin to visualize treated cells.…”

Elucidating the Impact ofHypericum alpestreExtract and L-NAME on the PI3K/Akt Signaling Pathway in A549 Lung Adenocarcinoma Cells

“…For the first time, we performed a combined treatment of breast cancer with HA herb extract and L-NAME in an in vivo experimental model of rat breast cancer [6]. This combination decreased tumor multiplicity, increased the amount of IL-2 in the tumor environment, activated antioxidant enzymes, and decreased histological score and tumor blood vessel area.…”

“…Phenolic compounds, as the most prevalent plant secondary metabolites, have attracted considerable attention due to their antioxidant/prooxidant properties and their potential role in the mitigation of diverse diseases associated with oxidative stress, including cancer. A total of 244 constituents were identified in H. alpestre extracts in our earlier research [6]. The metabolomic analysis of HA aerial part extracts using the UHPLC-ORBITRAP-HRMS technique unveiled the presence of several major phenolic constituents, suggesting that these substances might contribute to their high cytotoxic effects [7].…”

“…A total of 244 constituents were identified in H. alpestre extracts in our earlier research [6]. The metabolomic analysis of HA aerial part extracts using the UHPLC-ORBITRAP-HRMS technique unveiled the presence of several major phenolic constituents, suggesting that these substances might contribute to their high cytotoxic effects [7]. Considering the strong in vitro growth inhibiting properties of HA extract against different cancerous cell lines including the breast cancer model [7,8].…”