Betula etnensis Raf. (Birch Etna) belonging to the Betulaceae family grows on the eastern slope of Etna. Many bioactive compounds present in Betula species are considered promising anticancer agents. In this study, we evaluated the effects of B. etnensis Raf. bark methanolic extract on a human colon cancer cell line (CaCo2). In order to elucidate the mechanisms of action of the extract, cellular redox status, cell cycle, and heme oxygenase-1 (HO-1) expression in ferroptosis induction were evaluated. Cell viability and proliferation were tested by tetrazolium (MTT) assayand cell cycle analysis, while cell death was evaluated by annexin V test and lactic dehydrogenase (LDH) release. Cellular redox status was assessed by measuring thiol groups (RSH) content, reactive oxygen species (ROS) production, lipid hydroperoxide (LOOH) levels and (γ-glutamylcysteine synthetase) γ-GCS and HO-1 expressions. The extract significantly reduced cell viability of CaCo2, inducing necrotic cell death in a concentration-depending manner. In addition, an increase in ROS levels and a decrease of RSH content without modulation in γ-GCS expression were detected, with an augmentation in LOOH levels and drastic increase in HO-1 expression. These results suggest that the B. etnensis Raf. extract promotes an oxidative cellular microenvironment resulting in CaCo2 cell death by ferroptosis mediated by HO-1 hyper-expression.

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids’ potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades.

This study aims at investigating the contribution of two classes of compounds, flavonoids and iridoids, to the bioactivity of Arbutus unedo L. leaves and fruits. The impact of different extraction procedures on phytochemicals content and hypoglycemic, antioxidant, and nitric oxide (NO) inhibitory activities of A. unedo fresh and dried plant materials was investigated. Ellagic acid 4-O-β-D-glucopyranoside, kaempferol 3-O-glucoside, and norbergenin were identified for the first time in this genus by using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). Three iridoids (gardenoside, geniposide, unedoside) are specifically identified in the leaves. Interestingly, asperuloside was extracted only from dried fruits by ethanol with Soxhlet apparatus. Extracts were screened for their potential antioxidant activities by using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Activity Power (FRAP), and β-carotene bleaching tests. Based on the Global Antioxidant Score (GAS) calculation, the most promising antioxidant extract was obtained by hydroalcoholic maceration of dried leaves that showed half maximal inhibitory concentration (IC₅₀) of 0.42 and 0.98 μg/mL in ABTS and DPPH assays, respectively. The hypoglycaemic activity was investigated by α-amylase and α-glucosidase inhibition tests. Extracts obtained by ethanol ultrasound extraction of fresh leaves and hydroalcoholic maceration of fresh fruits (IC₅₀ of 19.56 and 28.42 μg/mL, respectively) are more active against α-glucosidase than the positive control acarbose (IC₅₀ of 35.50 μg/mL). Fruit extracts exhibited the highest anti-inflammatory activity.

Background: Salvia species are known for their biological properties in many countries and might potentially provide novel therapeutic agents. This review provides an overview of the available literature on the anti-inflammatory and antioxidant effects of Salvia species. Methods: Using bibliographic databases, particularly PubMed, this review aims to add new information to the list of Salvia species, including S. ceratophylla, S. chloroleuca, S. fruticosa, S. lachostachys, S. lavandulifolia, S. miltiorrhiza, S. mirzayanii, S. officinalis, S. plebeia, S. verbenaca, and S. virgata, and their main constituents as promising anti-inflammatory and antioxidant agents, highlighting their mode of action. Results: Salvia species are sources of health-promoting phytochemicals that comprise polyphenols, flavonoids, terpenes and several other constituents. Many studies have indicated that plants from the Salvia genus reduce the oxidative stress and may be able to prevent and/or to treat inflammatory diseases. These potential beneficial effects have been attributed to the presence of compounds that show antioxidant properties and that demonstrated to inhibit the molecular targets of pro-inflammatory mediators in inflammatory responses. Conclusion: Salvia species and their secondary metabolites may be potential agents to improve the quality of life in patients with inflammatory diseases.

The objective was to evaluate the effects of 6 months of supplementation with Altilix^®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix^® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix^® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (−2.40% (95% CI −3.79, −1.01); p < 0.001), waist circumference (−2.76% (95% CI −4.55, −0.96); p = 0.003), HbA1c (−0.95% (95% CI −1.22, −0.67); p < 0.001), plasma lipids, FLI (−21.83% (95% CI −27.39, −16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (−39.48% (95% CI −47.98, −30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix^® supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix^® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.