Maria Gulisano

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex^®G96^® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH.

Obesity is increasingly prevalent worldwide and is linked to metabolic diseases, such as insulin resistance (IR) and type 2 diabetes mellitus (T2DM), due to excessive free fatty acids (FFAs). Although lifestyle changes are effective, they often prove to be insufficient as initial treatments for obesity. Additionally, while surgical and pharmacological interventions are available, they are not entirely safe or effective. Recently, interest has grown in utilizing food waste and plant-derived phenolic compounds for their health benefits, presenting a promising avenue for managing obesity and its related disorders. Indeed, many studies have examined the potential inhibitory effects of the natural extract on adipocyte differentiation and lipid accumulation. This study focused on the evaluation of the effects of standardized extracts obtained from red oranges and olive leaf waste on 3T3-L1 murine pre-adipocyte and adipocyte functionality. Red orange extract (ROE) and olive leaf extract (OLE), alone and in combination, were tested to assess their anti-obesity and anti-inflammatory effects, as well as their potential therapeutic benefits. Three in vitro models were established to investigate the effects of the extracts on (I) adipocyte differentiation; (II) mature and hypertrophic adipocytes challenged with palmitic acid (PA) and erastin (ER), respectively; and (III) erastin-induced cytotoxicity on pre-adipocytes.

Benign prostatic hypertrophy (BPH) is a noncancerous enlargement of the prostate gland that develops from hyper-proliferation of the stromal and epithelium region. Activation of pathways involving inflammation and oxidative stress can contribute to cell proliferation in BPH and tumorigenesis. Agricultural-waste-derived extracts have drawn the attention of researchers as they represent a valid and sustainable way to exploit waste production. Indeed, such extracts are rich in bioactive compounds and can provide health-promoting effects. In particular, extracts obtained from pomegranate wastes and by-products have been shown to exert antioxidant and anti-inflammatory effects. This study focused on the evaluation of the anti-angiogenic effects and chemopreventive action of a pomegranate extract (PWE) in cellular models of BPH. In our experimental conditions, we observed that PWE was able to significantly (p < 0.001) reduce the proliferation and migration rates (up to 60%), together with the clonogenic capacity of BPH-1 cells concomitantly with the reduction in inflammatory cytokines (e.g., IL-6, PGE2) and pro-angiogenic factor (VEGF-ADMA) release. Additionally, we demonstrated the ability of PWE in reducing angiogenesis in an in vitro model of BPH consisting in transferring BPH-1-cell-conditioned media to human endothelial H5V cells. Indeed, PWE was able to reduce tube formation in H5V cells through VEGF level reduction even at low concentrations. Overall, we confirmed that inhibition of angiogenesis may be an alternative therapeutic option to prevent neovascularization in prostate tissue with BPH and its transformation into malignant prostate cancer.

Several studies have highlighted the ability of snail mucus in maintaining healthy skin conditions due to its emollient, regenerative, and protective properties. In particular, mucus derived from Helix aspersa muller has already been reported to have beneficial properties such as antimicrobial activity and wound repair capacity. In order to enhance the beneficial effects of snail mucus, a formulation enriched with antioxidant compounds derived from edible flower waste (Acmella oleracea L., Centaurea cyanus L., Tagetes erecta L., Calendula officinalis L., and Moringa oleifera Lam.) was obtained. UVB damage was used as a model to investigate in vitro the cytoprotective effects of snail mucus and edible flower extract. Results demonstrated that polyphenols from the flower waste extract boosted the antioxidant activity of snail mucus, providing cytoprotective effects in keratinocytes exposed to UVB radiation. Additionally, glutathione content, reactive oxygen species (ROS), and lipid peroxidation levels were reduced following the combined treatment with snail mucus and edible flower waste extract. We demonstrated that flower waste can be considered a valid candidate for cosmeceutical applications due to its potent antioxidant activity. Thus, a new formulation of snail mucus enriched in extracts of edible flower waste could be useful to design innovative and sustainable broadband natural UV-screen cosmeceutical products.