Background: Naringenin (NAR) is a flavonoid with excellent antioxidant and neuroprotective potential that is limited by its low solubility. Thus, solid dispersions with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropylmethylcellulose (HPMC), and microenvironmental pH modifiers were prepared. Methods: The systems formation analysis was performed by X-Ray Powder Diffraction (XRPD) and Fourier-transform infrared spectroscopy (FT-IR). Water solubility and dissolution rates were studied with a pH of 1.2 and 6.8. In vitro permeability through the gastrointestinal tract (GIT) and the blood-brain barrier (BBB) was assessed with the parallel artificial membrane permeability assay (PAMPA) assay. The antioxidant activity was studied with the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and cupric ion reducing antioxidant capacity (CUPRAC) assays, while in vitro enzymes studies involved the inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase. For the most promising system, in silico studies were conducted. Results: NAR solubility was increased 458-fold by the solid dispersion NAR:HP-β-CD:NaHCO3 in a mass ratio of 1:3:1. The dissolution rate was elevated from 8.216% to 88.712% in a pH of 1.2 and from 11.644% to 88.843% in a pH of 6.8 (within 3 h). NAR GIT permeability, described as the apparent permeability coefficient, was increased from 2.789 × 10−6 cm s−1 to 2.909 × 10−5 cm s−1 in an acidic pH and from 1.197 × 10−6 cm s−1 to 2.145 × 10−5 cm s−1 in a basic pH. NAR BBB permeability was established as 4.275 × 10−6 cm s−1. The antioxidant activity and enzyme inhibition were also increased. Computational studies confirmed NAR:HP-β-CD inclusion complex formation. Conclusions: A significant improvement in NAR solubility was associated with an increase in its biological activity.

Rosmarinic acid (RA) is a natural antioxidant with neuroprotective properties; however, its preventive and therapeutic use is limited due to its slight solubility and poor permeability. This study aimed to improve RA physicochemical properties by systems formation with cyclodextrins (CDs): hydroxypropyl-α-CD (HP-α-CD), HP-β-CD, and HP-γ-CD, which were prepared by the solvent evaporation (s.e.) method. The interactions between components were determined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier Transform infrared spectroscopy (FTIR). The sites of interaction between RA and CDs were suggested as a result of in silico studies focused on assessing the interaction between molecules. The impact of amorphous systems formation on water solubility, dissolution rate, gastrointestinal (GIT) permeability, and biological activity was studied. RA solubility was increased from 5.869 mg/mL to 113.027 mg/mL, 179.840 mg/mL, and 194.354 mg/mL by systems formation with HP-α-CD, HP-β-CD, and HP-γ-CD, respectively. During apparent solubility studies, the systems provided an acceleration of RA dissolution. Poor RA GIT permeability at pH 4.5 and 5.8, determined by parallel artificial membrane permeability assay (PAMPA system), was increased; RA–HP-γ-CD s.e. indicated the greatest improvement (at pH 4.5 from Papp 6.901 × 10−7 cm/s to 1.085 × 10−6 cm/s and at pH 5.8 from 5.019 × 10−7 cm/s to 9.680 × 10−7 cm/s). Antioxidant activity, which was determined by DPPH, ABTS, CUPRAC, and FRAP methods, was ameliorated by systems; the greatest results were obtained for RA–HP-γ-CD s.e. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was increased from 36.876% for AChE and 13.68% for BChE to a maximum inhibition of the enzyme (plateau), and enabled reaching IC50 values for both enzymes by all systems. CDs are efficient excipients for improving RA physicochemical and biological properties. HP-γ-CD was the greatest one with potential for future food or dietary supplement applications.

Glioblastoma (GBM) is an extremely aggressive brain tumor awaiting novel, efficient, and minimally toxic treatment. Curcuminoids (CCM), polyphenols from Curcuma longa, and sodium butyrate (NaBu), a histone deacetylase inhibitor naturally occurring in the human body, await elucidation as potential anti-GBM agents. Thus, the aim of this study was to analyze CCM and NaBu both separately and as a combination treatment using three GBM cell lines. MTT was used for cytotoxicity evaluation, and the combination index was calculated for synergism prediction. Cell cycle, apoptosis, and reactive oxygen species (ROS) generation were analyzed using flow cytometry. DNA methylation was verified by MS-HRM and mRNA expression by qPCR. The permeability through the blood-brain barrier (BBB) and through the nasal cavity was evaluated using PAMPA model. The results of this study indicate that CCM and NaBu synergistically reduce the viability of GBM cells inducing apoptosis and cell cycle arrest. These effects are mediated via ROS generation and changes in gene expression, including upregulation of Wnt/β-catenin pathway antagonists, SFRP1, and RUNX3, and downregulation of UHRF1, the key epigenetic regulator. Moreover, NaBu ameliorated CCM permeability through the BBB and the nasal cavity. We conclude that CCM and NaBu are promising agents with anti-GBM properties.

Cannabis leaves contain a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer significant health benefits. Utilising cannabis leaves as a source of antioxidants presents a cost-effective approach because they are typically discarded during the cultivation of cannabis plants for their seeds or fibres. Therefore, this presented study aimed to assess the antioxidant activity of the leaves of selected hemp cultivars, such as Białobrzeska, Tygra, and Henola, based on the results obtained with the 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, ferric reducing antioxidant power, cupric reducing antioxidant capacity, and 2,2-Diphenyl-1-picrylhydrazyl assays. The cannabinoid profile was analysed for the antioxidant activity to the contents of cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabinol (Δ9-THC), and cannabichromene (CBC), determined based on chromatographic assays. The following variables were tested: the impact of various extractants (methanol, ethanol, and isopropanol), and their mixtures (50:50, v/v, as well as extraction methods (maceration and ultra-sound-assisted extraction) significant in obtaining hemp extracts characterised by different cannabinoid profiles. The results revealed that the selection of extractant and extraction conditions significantly influenced the active compounds’ extraction efficiency and antioxidant activity. Among the tested conditions, ultrasound-assisted extraction using methanol yielded the highest cannabinoid profile: CBD = 184.51 ± 5.61; CBG = 6.10 ± 0.21; Δ9-THC = 0.51 ± 0.01; and CBC = 0.71 ± 0.01 μg/g antioxidant potential in Białobrzeska leaf extracts.

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