Targeting Nrf2 Signaling Pathway in Cancer Prevention and Treatment: The Role of Cannabis Compounds.

The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2. Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells-influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support. In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy.

Differences in the phenolic composition and antioxidant properties between Vitis coignetiae and Vitis vinifera seeds extracts.

Phenolic compounds were extracted from European and Japanese grapevine species (Vitis vinifera and V. coignetiae) seeds using 80% methanol or 80% acetone. The total content of phenolic compounds was determined utilizing Folin-Ciocalteu's phenol reagent, while the content of tannins was assayed by the vanillin and BSA precipitation methods. Additionally, the DPPH free radical and ABTS cation radical scavenging activities and the reduction power of the extracts were measured. The HPLC method was applied to determine the phenolic compounds, such as phenolic acids and catechins. The seeds contained large amounts of tannins and gallic acid and observable quantities of catechins, p-coumaric, ferulic and caffeic acids. The dominant form of phenolic acids in the extracts was the ester-bound form. The content of total phenolics was higher in the European grape V. vinifera seeds, which also contained more tannins, catechins and phenolic acids, except for caffeic acid. Extracts from V. vinifera seeds showed better radical scavenger properties and stronger reducing power. The total contents of phenolic compounds and tannins in acetone extracts were higher than in methanolic extracts. Acetone extracts also exhibited stronger antiradical properties as well as stronger reducing power.

Antioxidant activity of mulberry fruit extracts.

Phenolic compounds were extracted from the fruits of Morus nigra and Morus alba using methanol and acetone. The sugar-free extracts (SFEs) were prepared using Amberlite XAD-16 column chromatography. All of the SFEs exhibited antioxidant potential as determined by ABTS (0.75-1.25 mmol Trolox/g), DPPH (2,2-diphenyl-1-picrylhydrazyl) (EC(50) from 48 µg/mL to 79 µg/mL), and reducing power assays. However, a stronger activity was noted for the SFEs obtained from Morus nigra fruits. These extracts also possessed the highest contents of total phenolics: 164 mg/g (methanolic SFE) and 173 mg/g (acetonic SFE). The presence of phenolic acids and flavonoids in the extracts was confirmed using HPLC method and chlorogenic acid and rutin were found as the dominant phenolic constituents in the SFEs.

Comparative flavan-3-ol profile and antioxidant capacity of roasted peanut, hazelnut, and almond skins.

In the present study, the flavan-3-ol composition and antioxidant capacity of roasted skins obtained from the industrial processing of three commonly consumed tree nuts (i.e., peanuts, hazelnuts, and almonds), as well as fractions containing low and high molecular weight (LMW and HMW) flavan-3-ols, were studied with the aim of assessing their potential as a source of flavonoids. Roasted peanut and hazelnut skins presented similar total phenolic contents, much higher than that of almond skins, but their flavan-3-ol profiles, as determined by LC-ESI-MS and MALDI-TOF MS, differed considerably. Peanut skins were low in monomeric flavan-3-ols (19%) in comparison to hazelnut (90%) and almond (89%) skins. On the other hand, polymeric flavan-3-ols in peanut and almond skins occurred as both A- and B-type proanthocyanidins, but in peanuts the A forms (up to DP12) were predominant, whereas in almonds the B forms (up to DP8) were more abundant. In contrast, hazelnuts were mainly constituted by B-type proanthocyanidins (up to DP9). The antioxidant capacity as determined by various methods (i.e., total antioxidant capacity, ORAC, DPPH test, and reducing power) was higher for whole extracts from roasted hazelnut and peanut skins than for almond skins; however, the antioxidant capacities of the HMW fraction of the three types of nut skins were equivalent despite their different compositions and DPs. Nevertheless, the large variation in flavan-3-ol concentration, structural composition, type of interflavan linkage, and DP found among the three types of nut skins suggests large difference in their expected in vivo biological activities.

Antioxidant activity of hazelnut skin phenolics.

Phenolic compounds were extracted from hazelnut skin using 80% (v/v) aqueous acetone or methanol. The crude extracts were applied onto a Sephadex LH-20 column for two fractionations (Fr. I and Fr. II). Fr. I consisting of low-molecular-weight phenolics was eluted by ethanol, whereas Fr. II consisting of tannins was obtained using acetone/water (1:1, v/v) as the mobile phase. UV spectra of phenolic compounds present in the crude extracts and their fractions exhibited a maximum absorbance at 282 nm. The crude extracts and their fractions were examined for phenolic and condensed tannin contents as well as total antioxidant activity (TAA), antiradical activity against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, and reducing power. Results of these assays showed higher values when Fr. II containing tannins was tested, followed by crude extract, and Fr. I. Both 80% acetone and methanol were capable of extracting phenolics, but 80% acetone was a more effective solvent for the extraction of condensed tannins (p < 0.05). These results suggest that hazelnut skin can be considered as a value-added byproduct for use as dietary antioxidants.