Phenylalanine Butyramide: A Butyrate Derivative as a Novel Inhibitor of Tyrosinase.

Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).

Optimization and Validation of Procyanidins Extraction and Phytochemical Profiling of Seven Herbal Matrices of Nutraceutical Interest.

Several medicinal herbal plants are extensively used as sources of bioactive compounds with beneficial effects on human health. This study assessed the procyanidin and polyphenol profiles together with the antioxidant potential of seven herbal medical matrices. To achieve this aim, procyanidin extraction from grape pomace was optimized and validated by monitoring monomeric-trimeric procyanidins. The proposed quantification method was applied to the seven medical herbs, and it proved to be a very efficient protocol for procyanidin-rich extracts analysis. In addition, the Paullinia cupana Kunth. seed was identified as a very rich source of procyanidins (about 5 mg/g dry matrix of each dimeric and about 3 mg/g dry matrix trimeric) with high antioxidant properties. The polyphenolic profile was assessed by HPLC-HESI-MS/MS analysis. The in vitro antioxidant activity was evaluated by DPPH assay to explore the antioxidant properties of the extracts, which were substantially higher in Peumus boldus Molina leaves extracts (935.23 ± 169 µmol of Trolox equivalent/g of dry weight) concerning the other matrices. Moreover, a high Pearson coefficient value was observed between the total flavonoid content (TFC) and DPPH in comparison with the total polyphenol content (TPC) and DPPH, indicating flavonoids as the principal bioactive with antioxidant activity in the extracts.

Effects of Food-Derived Antioxidant Compounds on In Vitro Heavy Metal Intestinal Bioaccessibility.

Environmental contamination by heavy metals (HMs) has emerged as a significant global issue in recent decades. Among natural substances, food-deriving polyphenols have found a valuable application in chelating therapy, partially limited by their low water solubility. Thus, three different hydroalcoholic extracts titrated in quercetin (QE), ellagic acid (EA), and curcumin (CUR) were formulated using maltodextrins as carriers, achieving a powder with a valuable water solubility (MQE 91.3 ± 1.2%, MEA 93.4 ± 2.1, and MCUR 89.3 ± 2%). Overcoming the problem of water solubility, such formulations were tested in an in vitro simulated gastrointestinal digestion experiment conducted on a water sample with standardized concentrations of the principal HMs. Our results indicate that regarding the nonessential HMs investigated (Pb, Cd, As, Sb, and Hg), MQE has been shown to be the most effective in increasing the HMs' non-bioaccessible concentration, resulting in concentration increases in Cd of 68.3%, in As of 51.9%, in Hg of 58.9%, in Pb of 271.4, and in Sb of 111.2% (vs control, p < 0.001) in non-bioaccessible fractions. Regarding the essential HMs, MEA has shown the greatest capability to increase their intestinal bioaccessibility, resulting in +68.5%, +61.1, and +22.3% (vs control, p < 0.001) increases in Cu, Zn, and Fe, respectively. Finally, considering the strong relation between the antiradical and chelating activities, the radical scavenging potentials of the formulations was assayed in DPPH and ABTS assays.

Dermatitis Artefacta: A Retrospective Descriptive Study on 46 Patients.

INTRODUCTION: Self-induced dermatoses are self-inflicted skin lesions, whose occurrence patient denies responsibility for. OBJECTIVES: The aim of this study was to retrospectively investigate all the clinical records of dermatitis artefacta (DA) in order to put special focus on: a) epidemiological aspects; b) location, shape and additional features of the lesions; c) availability of psychiatric details in the records. METHODS: A retrospective observational descriptive study on 46 patients affected by dermatitis artefacta was conducted from January 2015 to March 2021. The only inclusion criterion was clinical or histological diagnosis of DA in patients for which we had clinical images. RESULTS: The most frequent type of lesions were erosions/excoriations and ulcers (14/46, 30.4% and 13/46, 28.3% respectively) followed by ecchymoses (9/46, 19.5%), vasculitis-like lesions (5/46, 10.9%), crusted plaques (3/46, 6.5%), scales (1/46, 2.2%) and erythema (1/46, 2.2%). Thirty-three percent of the medical records generically referred to the presence of psychiatric disorder, but none of them included a specific psychiatric diagnosis. CONCLUSIONS: In our study the main dermatologic lesions observed in DA were represented by excoriations and ulcers and that the shape and location of the lesions are essential for a correct diagnosis.

Annurca Apple Oleolite as Functional Ingredient for the Formulation of Cosmetics with Skin-Antiaging Activity.

The identification of natural remedies for the management of the skin aging process is an increasingly growing issue. In this context, ursolic acid (UA), a ubiquitous molecule, mainly contained in Annurca apple (AA) fruit, has demonstrated valuable cosmetic potential. To this end, in the current study, the AA oleolite (AAO, extract in sunflower oil containing 784.40 ± 7.579 µg/mL of UA) was evaluated to inhibit porcine elastase enzymatic reactions through a validated spectrophotometric method. AAO has shown a valuable capacity to contrast the elastase enzyme with a calculated IC50 of 212.76 mg/mL, in comparison to UA (IC50 of 135.24 µg/mL) pure molecules and quercetin (IC50 of 72.47 µg/mL) which are used as positive controls. In this context and in view of the valuable antioxidant potential of AAO, its topical formulation with 2.5% (w/w) AAO was tested in a placebo-controlled, double-blind, two-arm clinical study on 40 volunteers. Our results indicated that after 28 days of treatment, a significant reduction of the nasolabial fold (-7.2 vs. baseline T0, p < 0.001) and forehead wrinkles (-5.3 vs. baseline T0, p < 0.001) were registered in combination with a valuable improvement of the viscoelastic skin parameters, where skin pliability/firmness (R0) and gross elasticity (R2) were significantly ameliorated (-13% vs. baseline T0, p < 0.001 for R0 and +12% vs. baseline T0, p < 0.001 for R2). Finally, considering the positive correlation between skin elasticity and hydration, the skin moisture was evaluated through the estimation of Trans epidermal water loss (TEWL) and skin conductance.

Agri-Food Waste Recycling for Healthy Remedies: Biomedical Potential of Nutraceuticals from Unripe Tomatoes (Solanum lycopersicum L.).

Unripe tomatoes represent an agri-food waste resulting from industrial by-processing products of tomatoes, yielding products with a high content of bioactive compounds with potential nutraceutical properties. The food-matrix biological properties are attributed to the high steroidal glycoalkaloid (SGA) content. Among them, α-tomatine is the main SGA reported in unripe green tomatoes. This review provides an overview of the main chemical and pharmacological features of α-tomatine and green tomato extracts. The extraction processes and methods employed in SGA identification and the quantification are discussed. Special attention was given to the methods used in α-tomatine qualitative and quantitative analyses, including the extraction procedures and the clean-up methods applied in the analysis of Solanum lycopersicum L. extracts. Finally, the health-beneficial properties and the pharmacokinetics and toxicological aspects of SGAs and α-tomatine-containing extracts are considered in depth. In particular, the relevant results of the main in vivo and in vitro studies reporting the therapeutic properties and the mechanisms of action were described in detail.

Phytochemical investigation and antioxidant properties of unripe tomato cultivars (Solanum lycopersicum L.).

Unripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.

Natural Chalcones for the Management of Obesity Disease.

In the last decade, the incidence of obesity has increased dramatically worldwide, reaching a dangerous pandemic spread. This condition has serious public health implications as it significantly increases the risk of chronic diseases such as type 2 diabetes, fatty liver, hypertension, heart attack, and stroke. The treatment of obesity is therefore the greatest health challenge of our time. Conventional therapeutic treatment of obesity is based on the use of various synthetic molecules belonging to the class of appetite suppressants, lipase inhibitors, hormones, metabolic regulators, and inhibitors of intestinal peptide receptors. The long-term use of these molecules is generally limited by various side effects and tolerance. For this reason, the search for natural alternatives to treat obesity is a current research goal. This review therefore examined the anti-obesity potential of natural chalcones based on available evidence from in vitro and animal studies. In particular, the results of the main in vitro studies describing the principal molecular therapeutic targets and the mechanism of action of the different chalcones investigated were described. In addition, the results of the most relevant animal studies were reported. Undoubtedly, future clinical studies are urgently needed to confirm and validate the potential of natural chalcones in the clinical prophylaxis of obesity.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones.

Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. In this scenario, the aim of the present work was the design of an innovative multi-component nutraceutical formulation (NF) for the management of urinary stones consisting of a synergistic combination of natural aqueous extracts of Oreganum vulgare L. (1% of saponin), Urtica dioica (0.8% of ß-sitosterol), Phyllanthus niruri (15% of tannins w/w), and Ceterach officinarum in association with bromelain, K, and Mg citrate. To assess the potential of NF also in the treatment of uric acid (UA) stones, the effects on the expression of the cellular UA transporters OAT1 and URAT1 were investigated in a renal tubular cell line. In addition, the myorelaxant effect of NF was investigated in a human pulmonary artery smooth muscle cell (HPASMC) model resulting in a decreased muscle contractility of -49.4% (p < 0.01) compared to the control. The treatment with NF also showed a valuable inhibition of in vitro calcium-oxalate crystal formation, both in prevention (-52.3% vs. control, p < 0.01) and treatment (-70.8% vs. control, p < 0.01) experiments. Finally, an ischemic reperfusion rat model was used to evaluate the NF anti-edema effects, resulting in a reduction in the edema-related vascular permeability (Normalized Gray Levels, NGL = 0.40 ± 0.09, p < 0.01, -67.1% vs. untreated rats). In conclusion, the present NF has shown to be a promising natural alternative for managing urinary tract stones.