Crocus sativus L., commonly known as saffron, is a precious spice coming from Asia, in particular from Iran, the country leader in its production. The spice is derived exclusively from dried stigmas and it is the most expensive one in the world. The areas of application of saffron are multiple, in fact ranging across the food, drinks, pharmaceuticals and cosmetics sectors. As is the case with other phytochemicals, not only the final product but also saffron by-products are considered a valuable source of bioactive natural compounds. In fact, its healthy effects, especially as antioxidants and anti-inflammatories (via reducing pro-inflammatory cytokines), are well-recognized in internal medicine. In particular, its healthy effects are related to counteracting degenerative maculopathy, depression and anxiety, neurodegenerative diseases, metabolic syndrome, cancer and chronic kidney disease, by promoting glucose metabolism. In this review, we summarize the most important papers in which saffron has turned out to be a valuable ally in the prevention and treatment of these pathologies. Moreover, we would like to promote the use of saffron by-products as part of a bio-circular economy system, aimed at reducing wastes, at maximizing the use of resources and at promoting environmental and economic sustainability.

Hydrolyzable tannins (HTs) deriving from chestnuts have demonstrated, through numerous studies, the ability to exert multiple beneficial effects, including antioxidant and antimicrobial effects, on the lipid metabolism and cancer cells. The latter effect is very fascinating, since different polyphenols deriving from chestnuts were able to synergistically induce the inhibition of cancerous cells through multiple pathways. Moreover, the main mechanisms by which tannins induce antioxidant functions include: the reduction in oxidative stress, the ability to scavenge free radicals, and the modulation of specific enzymes, such as superoxide dismutase. HTs have also been shown to exert significant antimicrobial activity by suppressing microbial growth. The actions on the lipid metabolism are several, among which is the inhibition of lipid accumulation. Thus, tannins seem to induce a cardioprotective effect. In fact, through various mechanisms, such as the relaxation of the vascular smooth muscle, HTs were proven to be efficient against arterial hypertension. Therefore, the great number of studies in this field prove the growing interest on the utilization of natural bioactive compounds, such as HTs deriving from natural sources or obtained by circular economy models, as potential nutraceuticals or adjuvants therapies.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, the Middle East and the USA. While in ancient times pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, making it a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs), and its consumption appears to exert numerous healthy effects, in particular, in several pathological conditions as metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies have pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and dentistry represents a promising field, as it could enable the development of innovative natural adjuvant therapies and empower standard pharmaceutical therapies.

Background: Chronic kidney disease (CKD) will become the fifth leading cause of death in the world by 2040. It is fundamental to prevent and treat this pathology to reduce its impact on national health costs. This trial’s aim is to evaluate the effects induced by a combination of consumed functional foods (FFs) with adapted physical activity (APA) on the progression of CKD-related comorbidities. Methods: The study lasted 12 weeks. We divided 40 CKD patients into four groups: mixed (FF + APA), APA, FF and control group (usual care). The FFs were characterized by their total antioxidant capacity and antiradical activity. The APA was performed though an online training protocol, three times per week, 1 h each session. Results: At the end of the study, we observed, in the mixed group, a decrease in azotemia (p = 0.0272), diastolic blood pressure (p = 0.0169), and C-reactive protein (p = 0.0313), with increases in the FORD test (p = 0.0203) and fat free mass (p = 0.0258). The APA group showed a reduction in total cholesterol (p = 0.0039). Conclusions: The combination of FFs and APA can help counteract several CKD-related comorbidities, such as arterial hypertension, dyslipidemia and uremic sarcopenia, and improve the CKD patients’ quality of life.

Background: Extra virgin olive oil is a typical food of the Mediterranean area, obtained by pressing Olea europaea L. fruits. Its polyphenols have been studied for their antioxidant function and protective action against cancer and chronic kidney disease. In this in vitro study, we tested titrated extracts from Olea europaea L. on a human embryonic kidney 293 (HEK-293E) cell line, regarding their pro-apoptotic and antiproliferative capacities, using “ IncuCyte^® S3 Live-Cell Analysis System”. Materials and Methods: We selected Olea europaea L. active compounds like hydroxytyrosol (HT) and oleuropein (OLE). These extracts were tested at different concentrations and characterized by HPLC-DAD-MS for the content in secondary active metabolites. The real-time observation of cell behavior was performed by IncuCyte, which can quantitatively analyze the cell proliferation and death. Results: This study showed that all the tested extracts can significantly inhibit cellular growth at 50 µM but the reduced proliferation is not related to an increase in cellular apoptosis. Instead, the same analysis performed by using extracts at 100 µM reveals that they can inhibit cellular growth, further inducing cellular apoptosis. Conclusions: The results on the HEK-293E cells confirmed the antiproliferative and proapoptotic actions of active compounds from an Olea europaea L. matrix in this cell line.

Background: Metabolic syndrome (MetS) patients have impaired hypothalamic regulatory functions involved in food intake and energy expenditure and suffer from a state of meta-inflammation. Pre-clinical studies demonstrated that ultramicronized palmitoylethanolamide (PEA) acts both on the adipose tissue and the central nervous system, while hydroxytyrosol (HTyr) counteracts several types of dysmetabolism. Objectives: The aim of our randomized crossover double-blind placebo-controlled pilot study was to evaluate the potential effects of a food supplement (FS) containing a co-micronized formulation of PEA and rutin along with HTyr, combined with a tailored calorie-controlled Mediterranean diet, in patients with MetS. Methods: Nineteen patients were enrolled and block-randomized to an eight-week MD together with the FS or placebo. After a two-week washout period, the treatments were reversed. Data on laboratory parameters and those detected by capillary sampling, anthropometry, body composition analysis, ultrasound examination, blood pressure monitoring, the 36-Item Short-Form Health Survey questionnaire, handgrip strength test, and physical performance tests were collected at each time point (protocol code R.S. 262.22, registered on 20 December 2022). Results: At the end of the study, patients supplemented with the FS showed a significant reduction in body weight, body mass index, fat mass, and inflammation biomarkers (CRP and ESR), compared to placebo-supplemented patients. In contrast, the fat-free mass, phase angle, and body cell mass were increased in FS compared to placebo patients. Conclusions: Although preliminary, the results of our clinical study suggest that co-micronized PEA–rutin and HTyr may be of help against adiposopathy in patients with MetS.