Nutraceuticals

Plant-derived pharmaceuticals represent a highly compelling area of research and continue to attract significant interest from countries, regions, scientific communities, and pharmaceutical companies worldwide. Among these, α- and β-amyrins have been identified as high-value triterpenoid compounds with a broad spectrum of potential therapeutic properties, including anti-inflammatory, antidiabetic, antiatherosclerotic, analgesic, antigout, neuroprotective, anti-Parkinsonian, anticancer, antibacterial, and anti-HIV activities. Relevant information and data were obtained through comprehensive searches of major scientific databases, including Web of Science, Elsevier, and the National Library of Medicine. This study highlighted the pharmaceutical potential of α- and β-amyrins, supported by specific evidence from in vivo, in vitro, and clinical trials. Various extraction methods for α- and β-amyrins are discussed, followed by recommendations for future directions in the development of these compounds as pharmaceutical agents and functional food ingredients. This review highlights the therapeutic of α- and β-amyrin compounds in the prevention and treatment of various serious diseases worldwide, potentially opening new opportunities and directions for the pharmaceutical industry. Full article

The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article

Short-chain fatty acids (SCFAs) are metabolites derived from the fermentation of dietary fibre by gut bacteria. SCFAs function as essential regulators of host-microbiome interactions by participating in numerous physiological and pathological processes within the gastrointestinal (GI) tract. In recent years, the depletion of SCFAs has been increasingly linked to the pathogenesis of GI diseases. In this review, we summarize the current understanding of the therapeutic mechanisms of SCFAs in GI diseases, including inflammatory bowel disease, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, and acute pancreatitis. We next highlight potential therapeutic approaches that increase the endogenous production of SCFAs, including prebiotics, probiotics, and fecal microbiota transplantation. We conclude that, although SCFAs are promising therapeutic agents, further research is necessary due to variability in treatment efficacy, inconsistent clinical outcomes, and a limited understanding of SCFAs’ mechanisms of action. Full article

This study aimed to evaluate the impregnation process of apple slices with bioactive compounds (BCs) that were obtained from the richest antioxidant fruit powder extracts. Acaí, beetroot, blueberry, cranberry, dragon fruit, and pomegranate powders were assessed on their main BCs, antioxidant capacity (AC), and reducing power (RP) before and after heat treatment to select the extract with the highest and most stable BCs and AC. The effect of pH (3–7) and the total soluble solids (TSSs) (5–15%) on the BCs and AC of selected fruit powder extracts were also evaluated to decide which one should be used to impregnate apple slices. Results indicate that the pomegranate extract presented the highest BCs, AC, and RP among the fruit powders tested, even after heat treatment. Moreover, the TSSs did not affect the BCs from the pomegranate extract; however, pH affected the stability, showing higher values of BCs as the pH was reduced. Apple slices impregnated with pomegranate extract (pH 2) showed an increase in their total phenolic compounds, total anthocyanins, AC, and RP at 25.94, 3085.00, 19.80, and 56.94%, respectively, compared to control apple slices. This study indicates that reducing the pH of pomegranate extracts may increase their antioxidant compounds, showing a higher impregnation of them on apple slices. Full article

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. Full article

Endometrial stromal cells (EnSCs) undergo decidualization in response to progesterone. Decidualization facilitates spiral artery remodeling, immune tolerance in the endometrium, and fetal cell invasion and placentation—all essential for successful embryo implantation. Therefore, we aimed to investigate whether ergothioneine (EGT) plays a role in reproduction, particularly in decidualization and implantation. In this study, we found that solute carrier family 22 member 4 (SLC22A4), a specific transporter of EGT—a functional food ingredient with strong anti-aging properties—is upregulated in decidualized EnSCs. The effects of EGT were examined using uterine tissues from patients, primary cultured EnSCs, EnSC cell lines, and co-cultures with a fetal cell line. We observed a significant increase in SLC22A4 expression in secretory-phase human uterine tissue, decidualized EnSCs, and EnSC cell lines. We also found that EGT regulates insulin-like growth factor binding protein 1 expression, which promotes placentation. In co-cultures of EnSC and fetal cell lines, EGT upregulated ectonucleoside triphosphate diphosphohydrolase 1 and major histocompatibility complex, class I, G expression in fetal cell lines—both critical for placentation. These findings suggest that EGT is crucial to regulating decidualization and its markers, particularly insulin-like growth factor-binding protein 1, which contributes to placentation. Full article

Ergothioneine is a diet-derived antioxidant with emerging evidence of neuroprotective benefits, but no dose-ranging study has evaluated its effects in healthy older adults. In this 16-week randomized, double-blind, placebo-controlled trial, 147 adults aged 55–79 with subjective memory complaints received ergothioneine (10 mg or 25 mg/day ErgoActive^®) or placebo. The primary outcome was the change in composite memory (CNS Vital Signs). Secondary outcomes included other cognitive domains, subjective memory and sleep quality, and blood biomarkers. At baseline, participants showed slightly above-average cognitive function (neurocognitive index median = 105), with plasma ergothioneine levels of median = 1154 nM (interquartile range = 889.9). Plasma ergothioneine increased by ~3- and ~6-fold for 10 mg, and ~6- and ~16-fold for 25 mg, at weeks 4 and 16, respectively (p < 0.001). 25 mg ergothioneine showed a within-group improvement in composite memory at week 4 (p < 0.05), although this was not sustained. Reaction time improved in both groups, dependent on time. Other domains showed null or limited effects. Subjective prospective memory and sleep initiation improved dose-dependently, with significant effects at 25 mg (p < 0.05). Liver function improved and a within-group increase in telomere length was noted. In conclusion, ergothioneine supplementation was safe and well tolerated, with evidence suggesting some benefits in this cohort of healthy older adults. Longer trials in individuals with lower baseline ergothioneine or cognitive function are warranted. Full article

This study aimed to evaluate the effects of ButyraGen^®, a direct butyrate generator, on digestive health in a real-world setting. A 6-week, randomized, double-blind, placebo-controlled, virtual clinical study was conducted starting with 596 participants. Participants were randomly assigned to either the 200 mg ButyraGen^® active or placebo group. Questionnaires were administered electronically to assess gastrointestinal health outcomes. Statistically significant improvements were observed in belly pain for the active ButyraGen^® group compared with the placebo group, particularly in women, and particularly in post-menopausal women. The active group showed a higher likelihood of achieving clinically significant improvements in digestive health measures. ButyraGen^® supplementation demonstrated statistically significant benefits in rapidly improving gastrointestinal health and quality of life, especially in women and those with upper and lower GI symptoms. Full article

Background/Objectives: The term “nutraceuticals” refers to food and dietary supplements promoted for their health benefits in addition to their nutritional value. These products contain plant- or animal-derived nutrients, vitamins, minerals, trace elements, and similar compounds aimed at enhancing skin health and influencing visible skin quality. This review provides an overview of the current research on nutraceuticals and the scientific evidence supporting their effects on skin health. Methods: The literature on more than 50 selected nutraceuticals was examined to assess any clinically substantiated, beneficial effects on skin health. The assessment was based on scientific evidence, including the quality and quantity of empirically gathered and evaluated findings. Results: A total of 17 common dietary supplements, either as individual compounds or categorized into groups, along with some combination products, were identified as nutraceuticals with well-supported effects on skin health. These include, among others, vitamins A, B7, C, and E; collagen peptides; carotenoids; and various plant extracts. For many other nutraceuticals, clinical evidence for their effects on skin health is limited or insufficient. Conclusions: The literature indicates that many nutraceuticals marketed for skin health are more or less suitable for this application based on the evidence assessment. Full article

Cherries are well known to be a rich source of (poly)phenols, especially anthocyanins, with exhibited antioxidant and anti-inflammatory properties. The aim of this review is to describe the effects of cherry extract observed in clinical trials and the respective tolerability indications, highlighting the differences in efficacy depending on the type of extract, cherry, formulation, and dosage used. In particular, the supplementation of standardized tart cherry extracts has been shown to improve different markers of human health, exercise performance, and quality of sleep. Most clinical studies conducted to date have reported the total (poly)phenol and anthocyanin doses administered that were contained in cherry extracts, which ranged from 143 to 2140 mg/day and 15 to 547 mg/day, respectively, as well as the duration of treatments, which ranged from acute supplementation to 84 days. Although cherry extracts are currently prescribed as dietary supplements in several areas of medicine, further investigations of the mechanisms of action and long-term randomized clinical trials (RCTs) are required in order to validate the efficacy and safety of clinical applications. In addition, a real challenge for the next few years is the standardization of cherry’s (poly)phenolic fractions. In this context, the optimization of the extraction procedure and downstream processing represents a key point in reliable active guiding principles for the formulation of food supplements. In fact, due to the different extraction methods of cherries, the relative efficacy is closely related to the specific (poly)phenol profile obtained, which cannot be extrapolated from the literature. Future research should include an analysis reporting the total (poly)phenol content and the specific analytical methods used to quantify total and individual anthocyanin contents. Full article

The solid-state fermentation (SSF) of agro-industrial by-products such as okara, pomegranate peel, and cranberry pomace presents a sustainable approach to enhance the release of bioactive compounds. This study investigated the effects of different microbial cultures—Rhizopus oligosporus, Aspergillus oryzae, Streptococcus thermophilus, and a co-culture of R. oligosporus and S. thermophilus—on the bioconversion of bioactive compounds in 100% okara, okara with 2% pomegranate peel, and okara with 1% cranberry pomace. The objective was to assess whether co-culture fermentation with molds and S. thermophilus augments the release of bioactive compounds in okara-based fermentations through synergistic enzymatic activity. Over a period of 72 h, isoflavone transformation (daidzin, daidzein, genistin, and genistein), pH evolution, and water activity were assessed. The co-culture system exhibited improved bioconversion, leading to significant (p < 0.01) increases in daidzein and genistein in pure okara compared to the starting material. The highest polyphenol content (0.908 mg/g) and antioxidant capacity (24.9 mg Trolox eq/g) were recorded in 100% okara. However, pomegranate peel inhibited β-glucosidase activity, delaying the release of isoflavone aglycones. These findings confirm that co-culture fermentation is an effective strategy for enhancing the bioactive properties of okara-based fermentations. This facilitates the release of bioactive aglycones and supports the upcycling of agro-industrial by-products into functional food ingredients. Future research should focus on optimizing fermentation parameters to further enhance the release of bioactive compounds. Full article

This feasibility study investigates the relationship between functional food consumption and mental well-being, focusing on natural foods traditionally linked to mental health benefits. This research also examines consumer preferences to identify key characteristics that novel functional foods designed to enhance mental well-being should possess. Additionally, this study lays the groundwork for a clinical trial exploring the effects of a novel functional food on mental health and well-being. Data were collected through an online bilingual survey (Greek/English) from 362 participants across Greece and Cyprus, using an adapted Functional Food Frequency Questionnaire (FFFQ) featuring 30 foods with documented effects on cognitive function and mood regulation. The survey included validated scales measuring mental well-being, health-related quality of life (HRQoL), sleep quality, and food choice motives, along with demographic and anthropometric data. Analysis revealed significant associations between functional food consumption and mental health outcomes, particularly in HRQoL, sleep quality, and body mass index (BMI). Most functional foods consumed were natural and aligned with the Mediterranean dietary pattern, such as fruits, vegetables, nuts, herbal infusions, and honey, all demonstrating positive effects on mental and physical health. Consumer preferences showed a strong inclination toward functional foods that balance sensory appeal with health benefits, including milk-based and plant-based beverages, protein bars, and granola bars. Ingredients like St. John’s wort and Greek mountain tea were identified as potentially beneficial for mental well-being, consistent with their established efficacy in psychological health. A significant majority of participants (66.9%) expressed interest in participating in clinical trials, highlighting the need for further research into the efficacy of functional food components. This study provides a foundation for future clinical trials examining the impact of novel functional food formulations on mental and physical health, addressing the growing consumer demand for products that enhance psychological resilience and well-being. Full article

In these times and with the pace of life that we have developed, many people need help falling asleep due to poor sleep hygiene, among other reasons. Thus, in mild cases, it is recommended to use natural therapies, such as phytotherapy, avoiding in the first instance the use of drugs. Melatonin is considered a versatile molecule widely used today. It is included as a main ingredient in dietary supplements that are, in some cases, accompanied by medicinal plants as botanical mixes, generating beneficial products for sleep disorders among other conditions. The dietary phytotherapeutic supplements evaluated in this work contain various concentrations of melatonin and other products, resulting in different effects on sleep therapy. The aim of this work is to reveal the quantitative differences that exist between the melatonin contents labeled in the products and those analyzed. The degradation rate of this hormone at three years in the phytotherapeutic supplements is also studied in order to re-evaluate the expiration dates of these products. In conclusion, the mixture between synthetic melatonin and different botanical mixes is very common in the supplements studied here and aimed at improving sleep. However, the most natural thing would be to be able to use only plants with sufficient phytomelatonin content to eliminate the inclusion of chemically synthesized melatonin in preparation. We propose the use of a particular raw plant material with excellent characteristics for this purpose. Full article

Lyophilized organ extracts from livestock such as beef or elk are widely commercially proposed as animal-sourced nutraceuticals. Such preparations contain blends of vitamins and nutrients that may be employed for general or specific dietary supplementation. The first objective of this study was to develop an optimized and function-oriented manufacturing process for stabilized organ-specific extracts of American buffalo (Bison bison). The second objective of the study was to perform functional benchmarking of the obtained stabilized extracts by focusing on antioxidant attributes, which are key properties of nutraceuticals. Methodologically, a two-step lyophilization process, hard-shell capsule formulation, and process quality control elements were adapted from pharmaceutical technology practices. Stabilized extracts (300 mg capsules) were derived from the spleen, heart, liver, kidneys, lungs, and thymus of grass-fed and grass-finished American bison (born and raised in a tempered climate in Geneva, Switzerland). Functional benchmarking of the obtained extracts was performed using orthogonal methods of antioxidant activity determination (TEAC, FRAP, and H₂O₂ challenge assays). Firstly, the developed biomass transformation process enabled the considered organs to be effectively stabilized while reaching the desired quality attributes. Secondly, functional characterization of the formulated extracts revealed significant and organ-specific antioxidant attributes, wherein liver-derived materials were found to be the most potent. Thirdly, key quality and functional parameters (residual moisture levels and TEAC) were found to be stable over 12 months of storage following extract preparation. Overall, the present study provides an evidence-based technical/functional rationale for the preparation and control of American bison organ-specific lyophilized extracts to be included in nutraceutical preparations. Full article

The aim of the present study was to investigate the phenolic composition and the efficacy of an innovative formulation based on Mg, Vitamin B6, and water extracts from Vitex agnus-castus, Crocus sativus, Melissa officinalis, Betula pendula, and Betula pubescens developed as an effective tool to face neuroinflammation and depression symptoms occurring in premenstrual syndrome (PMS). The formulation was analyzed through colorimetric and liquid chromatography methods for determining the content in phenols and flavonoids. Additionally, scavenging/reducing properties were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH,) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and horseradish peroxidase assays. The biocompatible limits were determined via allelopathy, the brine shrimp lethality test, and Daphnia magna cardiotoxicity assay. The formulation was then assayed in an experimental model constituted by isolated mouse cortex specimens exposed to K⁺ 60 mM Krebs–Ringer buffer, a toxic depolarizing stimulus able to reproduce the burden of inflammation/oxidative stress and the increased serotonin (5-hydroxytryptamine, 5-HT) impoverishment occurring in different neurological and psychiatric conditions, including depression. The results of the phytochemical analysis showed that the formulation is rich in benzoic acids, namely gentisic acid (155.31 µg/mL) and phenylethanoid compounds, namely hydroxytyrosol (39.79 µg/mL) that support the antioxidant effects measured via DPPH (IC₅₀: 1.48 mg/mL), ABTS (IC₅₀: 0.42 mg/mL), and horseradish peroxidase (IC₅₀: 2.02 mg/mL) assays. The ecotoxicological models indicated the formulation as non-toxic, permitting the identification of a biocompatible concentration (1000 µg/mL) to be used in isolated mouse cortex exposed to K⁺ 60 mM Krebs–Ringer buffer. In this model, the gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), estrogen receptor-1 (ESR1), prolactin receptor (PRLR), brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) was determined by real-time PCR. In the isolated mouse cortex, the formula reduced COX-2, IL-6, SERT, ESR1, and PRLR gene expression and increased BDNF and IL-10 gene expression. Overall, the study corroborated the use of the formulation as an innovative tool to contrast inflammation, oxidative stress, and neurotransmitter impairment associated with PMS. Full article

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol is known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol’s impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol’s efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peritumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol’s influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced in the melanoma model after stroma deterioration caused xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol’s mechanisms of action and its role in cancer therapy. Full article

The use of plants for therapeutic purposes is an ancestral practice that dates back to the earliest times in the history of mankind. Even today the exploitation of plants for medicinal purposes plays a big role for the communities, especially in Africa, despite advances in modern medicine. According to the World Health Organization, about 80% of the population in developing countries use plants for their primary health care. In Niger, the use of medicinal plants is a foundation of traditional medicine across all ages. It remains a very common practice, especially in rural areas. This practice concerns all ages of life, including mother–child care. In infants and young children, mothers use plants as fortifiers for their prophylactic or curative powers, or to facilitate growth and weight gain, and also to fight major causes of infant morbidity and mortality. Mothers also use medicinal plants for their galactogenic power to stimulate lactation. This is even more important in rural areas where breastfeeding is the main source of infant nutrition. Over the years, these medicinal plants have been the subject of chemical and biological investigations to back up their therapeutic potential and virtues. This study aims to summarize current knowledge on the most commonly used medicinal plants in Niger in mother–child care. This helps emphasize the validation of ancestral medicinal plants through the scientific evaluation of the bioactive components and mechanisms. Elements of sustainability are discussed in future developments. Full article