Nutraceuticals

Angiogenesis, the process of forming new blood vessels from existing ones, is crucial in both physiological and pathological conditions, such as tumor growth, metastasis, and inflammatory disorders. Targeting angiogenesis has emerged as a promising therapeutic strategy. Recent research has increasingly focused on the role of bioactive components found in food in regulating angiogenesis, although there are certain limitations. This review provides a comprehensive examination of the origins, composition, pharmacological activities, and mechanisms of action of these components in medicinal foods, reflecting the growing intersection of medicine and nutrition. The goal is to aid in preventing angiogenesis-related complications and fostering healthier habits. The insights offered in this review aim to advance the development of effective, low-toxicity antiangiogenic drugs. Additionally, there has been a notable rise in interest in plant-derived compounds with antiangiogenic properties. This review investigates the potential of phytoconstituents from plants as drug candidates targeting angiogenesis, exploring their mechanisms of action, the research conducted thus far, and the challenges associated with transitioning these compounds into clinical applications. Full article

Red clover (Trifolium pratense L.) is found in southeast Europe and Anatolia. Its primary traditional medicinal use includes the treatment of various conditions of the upper respiratory tract. In recent years, its isoflavones have become the focus of research aimed at developing treatments to alleviate menopausal symptoms. Reduced levels of circulating estrogen due to reduced ovarian function can cause short-term symptoms such as hot flashes, palpitations, difficulty sleeping, headaches, fatigue, mood disorders and reduced concentration but also long-term chronic conditions, such as cardiovascular disease, accelerated weight and bone mass loss, atrophic vaginitis, osteoporosis, and cognitive impairment. The aim of this narrative review was to analyze the effects of commercially available and standardized red clover extracts on menopausal women. Eight randomized controlled trials on a total of 8769 menopausal women (aged 40 to 65 years) evaluated the effect of red clover isoflavone extract on menopausal symptoms. In all studies, isoflavone extract treatment showed improvement in all menopausal symptoms, including some common comorbidities, namely, hot flashes (1487 women, 25%), blood lipids (1155 women, 19%), atherosclerosis (6938 women, 79%), risk of breast cancer and endometrial cancer (428 women, 5%), osteoporosis and osteopenia (555 women, 6%), and menopause-related cognitive impairment (3530 women, 40%). Full article

Avocado seed contains 64% of the phenolic compounds of the whole fruit. This makes avocado seed a potential candidate for the development of treatments for different illnesses, including obesity (the major risk factor for metabolic disorders). The aim of this study was to investigate the effects of avocado seed powder on high-fat diet-induced obesity in rats. Sprague Dawley rats (16 rats) were fed a high-fat diet for 10 weeks. After 10 weeks, the rats were assigned into two groups of eight animals each and were fed either a high-fat diet (HFD; control group) or a high-fat diet containing avocado seed powder (HFD-A; treatment group) for 6 weeks. Animals were weighed weekly, and weekly weight gain was determined. Animals in the treatment (avocado seed) group showed significantly lower body weight gain (7.8 ± 9.63 g) than animals in the control group (33.9 ± 10.84 g) at the end of this study. The treatment group presented with lower triglycerides than the control, with LDL and HDL comparable to the control group. Avocado seed powder showed potential to reduce obesity in rats fed a high-fat diet. Avocado seed can therefore be investigated further as a potential anti-obesity nutraceutical. Full article

γ-Tocopherol (γT) is the major form of vitamin E contained in plants and seed oils. Although it is readily metabolized in the liver, the function of the metabolites is not fully understood. This study investigated the antioxidant activities of the γT metabolite 2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman (γCEHC) in comparison to its parent compound. The pretreatment of mouse hepatoma Hepa1c1c7 cells with γCEHC showed a cytoprotective effect on the hydrogen peroxide-induced cytotoxicity to a lesser extent than that of γT. A mechanistic investigation revealed that both γ-CEHC and γT significantly up-regulated the gene and protein expressions of heme oxygenase-1 (HO-1) via the promotion of the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the combination of γCEHC and γT significantly increased the gene and protein levels of HO-1 and the nuclear translocation of Nrf2, suggesting that it was an additive effect. Tin protoporphyrin IX (SnPP), a representative HO-1 inhibitor, significantly impaired the cytoprotection of γCEHC and γT against the hydrogen peroxide-induced cytotoxicity. These results suggested that not only γT but also its metabolite, γCEHC, are a promising cytoprotective factor against oxidative stress-induced cytotoxicity and that the cytoprotective effect is attributable to the cooperation of both compounds. Full article

The enteric nervous system (ENS) interacts bidirectionally with the local immune system, responding to inflammation within the gastrointestinal (GI) tract. In a previous study using the same samples, several gene targets were identified as being differentially expressed in the inflamed colonic tissue of pigs challenged with dextran sodium sulphate (DSS). Additionally, animals in the basal DSS group, exhibited reduced growth and increased fecal and pathology scores, while the relative abundance of beneficial taxa was reduced and harmful bacteria increased. While changes in the innate immune response and barrier function are widely cited regarding inflammatory bowel disease (IBD), the effects of inflammation on the local structures of the enteric nervous system (ENS) are less well understood. Hence, the objectives of this study were to: (1) evaluate the expression of a range of functionally diverse neuroactive receptors, transporters and neurotrophic factors in RNA derived from the colonic tissue from the same pigs; (2) examine associations with these neuroactive components and inflammatory, barrier function and matrix remodeling targets. Mature pigs were split into two experimental groups: (1) basal diet (n = 10); (2) basal diet + DSS (n = 11). The pigs were orally challenged with DSS once daily for four days and sacrificed humanely. Colonic tissue was collected for gene expression analysis. Most of the targets evaluated in this study were present at low levels or in some cases were undetectable by QPCR, including the dopamine receptor DRD5 and the serotonin receptor HTR3A. The dopamine receptors (DRD1, DRD3, DRD4), serotonin receptor (HTR4), and other selected neuroactive receptors (GRM7, GABRA2) were down-regulated in the DSS-challenged animals relative to the basal group (p < 0.05). Most notably, DRD2, was up-regulated four-fold, suggesting an active process involving this receptor (p < 0.05). Relationships with (previously published) gene expression data from the same samples suggest that DRD1 and DRD2 are influenced by different pathways and may also be interlinked with matrix remodeling and, more specifically, genes relevant to the epithelial to mesenchymal transition (CDH1, CDH2, IL6, IL13, IL10, MMP1, MMP2) an important fibrotic process in the pathogenesis of IBD. Full article

Colorectal cancer is the third leading cause of cancer-related deaths, and the five-year survival rate of the metastatic disease is less than 15%. Treatment approaches include surgery, systemic chemotherapy and radiotherapy. The aggressive nature and low five-year survival rate of metastatic colorectal cancer indicate a need for new treatment options to help combat this disease. Ursolic acid is a pentacyclic triterpenoid naturally occurring in many plants, with high concentrations found in cranberries. This review summarizes evidence from the last ten years of the effects of ursolic acid on colorectal cancer. Overall, the available studies indicate that the treatment of colon cancer cells with ursolic acid results in a significant inhibition of proliferation and induction of apoptosis. In addition, the limited in vivo studies indicate a significant reduction in tumor volume and tumor angiogenesis in animal models of colorectal cancer administered ursolic acid. More in vivo animal studies are required to better understand the potential anticancer properties of ursolic acid and to form the basis for human clinical trials. Full article

Jabuticaba fruit (Plinia cauliflora) is widely consumed in various forms such as juice, jam, wine, and liquors; however, its potential therapeutic effects on diabetic complications remain inadequately explored. We aimed to investigate the potential antiglycation activity of Jabuticaba, identify the active compounds through bioassay-guided fractionation, and assess its effects on cataract formation in a Streptozotocin-induced diabetic type 1 rat model. Through bioassay-guided fractionation, we identified gallic acid (IC₅₀: 24.7 µg/mL), protocatechuic acid (IC₅₀: 1.22 µg/mL), and an ellagitannin, Repandinin B (IC₅₀: 0.55 µg/mL), as active compounds contributing to antiglycation effects. In the animal study, the addition of Jabuticaba juice extract to the drinking water at a concentration of 0.5% (w/v) for 12 weeks demonstrated an amelioration in cataract progression. These results suggest that Jabuticaba has high antiglycation effects leading to the delaying of cataract formation in type 1 diabetes. Full article

Seaweeds have been utilized for millennia in Asian countries, although they have only more recently become popular in Western society. They began to be used in ancient times because of their long-term properties and, nowadays, seaweeds are being targeted as a potential tool to combat climate change. There are not many laws governing seaweeds because they have just lately been utilized as food. However, guidelines are being developed to regulate their manufacture and use. Because of seaweed’s tendency to accumulate components, whether helpful or poisonous, limited doses of certain substances have been established to prevent consumer overdosage. Aside from chemical safety, microbiological safety is important for people, and preventing any pathogen from spreading and infecting seaweeds is critical. As a result, systems and ways to safeguard consumers must be developed. Because various seaweed species have varied compositions, certain seaweeds may be safer nutraceuticals than others. To ensure the safety of seaweed-based food items, the HACCP (Hazard Analysis Critical Control Point) system needs to be used. The majority of seaweeds consumed come from aquaculture; however, others come from wild harvesting. To ensure the success of the cultures, the waters must be tested for chemicals and biological risks, as well as for the pH, salinity, and temperature. Seaweeds have enormous promise in many industries, but in the food industry, they are beginning to play a major role, and seizing the chances to produce innovative, safe, and sustainable food sources is strongly advised. This critical review investigates the real potential of seaweed as a human food source and as a nutraceutical solution. This review also focuses on the usage of seaweed as a food product and the procedures required to prepare it. In addition, it compiles information on the applicable legislation and regulations, and it addresses the lengthy road that has to be traveled to increase human well-being by employing a new food source in a controlled manner while simultaneously reducing the human population’s health problems. Full article

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. The psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine. Full article

Euglena gracilis (EG) microalgae has immune-modulating properties, partly due to its unique intracellular β-glucan-granules (paramylon). We evaluated the effects of EG consumption on immune status in vivo, ex vivo, and in vitro. A placebo-controlled cross-over study evaluated acute immune surveillance, followed by a 1-week open-label phase. Immune training was documented using ex vivo immune challenges and cytokine profiles. In vitro testing of monocytes compared the effects of EG to pure β-glucan. Compared to placebo, EG consumption triggered increased T cell numbers in the blood circulation (1 h: p < 0.01) and decreased monocyte numbers (2 h: p < 0.05). Natural killer cells showed increased CD25 expression (1 and 2 h: p < 0.01) and reduced CD69 expression (2 h: p < 0.01). T cells showed reduced CD25 and CD69 expression (p < 0.01). There were no significant changes to serum cytokines. After EG consumption, ex vivo cultures of peripheral blood mononuclear cells showed significant changes to spontaneous and inflammation-induced cytokine levels after 2 h (increased G-CSF: p < 0.01, reduced IL-1β and TNF-α (p < 0.05)) and one week (reduced TNF-α (p < 0.01) and increased IL-10 (p < 0.05)). In vitro, EG-trained monocytes responded differently to a second stimulus than β-glucan-trained monocytes (increased IL-1b: p < 0.1, TNF-α: p < 0.01). EG-mediated training of innate immunity, combined with long-term modulation of inflammation, suggests a nutraceutical strategy for preventive immune support. Full article

The present study screened various fungal species for inhibitors of alpha-glucosidase, alpha-amylase, and DPP-4, enzymes that are crucial in carbohydrate metabolism. Ethanolic extracts exhibited superior inhibitory activity compared to water extracts, suggesting their potential as sources of anti-diabetic agents. Further fractionation revealed fomentariol from Fomes fomentarius as a potent inhibitor of alpha-glucosidase and DPP-4, with higher activity against alpha-glucosidase than acarbose. Fomentariol presents a novel avenue for diabetes management, demonstrating the simultaneous inhibition of key enzymes in glucose metabolism. However, comprehensive clinical studies are needed to evaluate its safety and efficacy in humans. Full article

Melatonin (MLT), a natural compound found in the animal and vegetable kingdom, participates in several physiological processes. MLT exerts antioxidant and anti-inflammatory activities, among others, but information about its action on lipid metabolism is still scarce. For this reason, mice deficient in apolipoprotein E (ApoE^−/−) fed a Western diet (WD) were intragastrically treated with different concentrations of MLT (2 and 9 mg/kg) for 12 weeks. The lipid parameters were quantified, and, since links between cardiovascular risk and immune function and oxidative stress have been established, we also analyzed the population of leukocytes and the oxidative stress status. Although there was no change in the weight of the mice, a significant reduction in low-density lipoprotein cholesterol (LDL-C) was observed in mice treated with the higher concentration of MLT tested in this study. Additionally, an improvement in cardiovascular risk indexes was observed. A reduction in the hepatic total cholesterol (TC) and LDL-C levels was also observed in the treated mice. Finally, a decrease in leukocytes and lymphocytes in particular, as well as an increase in the antioxidant status, were shown in MLT-treated mice. In conclusion, MLT is a promising candidate that could be considered as a possible functional ingredient capable of preventing cardiovascular risk. Full article

Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical role of GABA in disease-free brain function. The review examines the intricate interplay between the gut–brain axis and CNS function. The potential impact of dietary GABA on the brain, either by traversing the blood–brain barrier (BBB) or indirectly through the gut–brain axis, is explored. While traditional beliefs questioned GABA’s ability to cross the BBB, recent research challenges this notion, proposing specific transporter systems facilitating GABA passage. Animal studies provide some evidence that small amounts of GABA can cross the BBB but there is a lack of human data to support the role of transporter-mediated GABA entry into the brain. This review also explores GABA-containing food supplements, investigating their impact on brain activity and functions. The potential benefits of GABA supplementation on pain management and sleep quality are highlighted, supported by alterations in electroencephalography (EEG) brain responses following oral GABA intake. The comprehensive overview encompasses GABA’s sources in the diet, including brown rice, soy, adzuki beans, and fermented foods. GABA’s presence in various foods and supplements, its association with gut microbiota, and its potential as a therapeutic strategy for neurological disorders are thoroughly examined. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords “GABA”, “oral GABA“, “sleep”, “cognition”, “neurodegenerative”, “blood-brain barrier”, “gut microbiota”, “supplements” and “therapeutic”, and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that suggest oral GABA benefits range from neuroprotection to blood pressure control. The literature suggests that oral intake of GABA affects the brain illustrated by changes in EEG scans and cognitive performance, with evidence showing that GABA can have beneficial effects for multiple age groups and conditions. The potential clinical and research implications of utilizing GABA supplementation are vast, spanning a spectrum of diseases ranging from neurodegeneration to blood pressure regulation. Importantly, recommendations for the use of oral GABA should consider the dosage, formulation, and duration of treatment as well as potential side effects. Effects of GABA need to be more thoroughly investigated in robust clinical trials to validate efficacy to progress the development of alternative treatments for a variety of disorders. Full article

This study investigated the effect of a commercially available ketone supplement on heart rate (HR), perceived exertion (RPE), blood lactate, glucose, and ketone concentrations, along with time to fatigue (TTF) during a running task to voluntary fatigue. Twelve NCAA Division I cross-country athletes took part in this randomized, double-blind, placebo-controlled cross-over study. Bayesian methodologies were employed for all statistical analyses, and point estimates were determined to be statistically significant if the 95% highest-density intervals (HDI) excluded zero. TTF was not significantly different between conditions with a Mean_diff = 48.7 ± 6.3 s (95% HDI: −335, 424) and a 0.39 probability derived from the posterior distribution, indicating the likelihood that the supplement would increase TTF compared to the placebo control. Lactate concentrations immediately post-exercise were significantly lower in the supplement trial relative to placebo with an estimated Mean_diff = −4.6 ± 1.9 mmol; 95% HDI: −8.3, −0.9. There were no significant interaction effects observed for either blood glucose or ketone concentrations nor HR or RPE. These findings imply that the acute ingestion of ketones before running at lactate threshold pace has a low probability of increasing TTF in highly trained Division I runners. Full article

All over the world, wild edible plants are an essential source of chemical components that justify their use in folk medicine. The aim of this review is to document and summarize the knowledge of ten wild plants analyzed in a previous study for their ethnomedical significance. Achillea millefolium, Borago officinalis, Foeniculum vulgare, Gentiana lutea, Juniperus communis, Laurus nobilis, Malva sylvestris, Satureja montana, Silybum marianum and Urtica dioica were the subjects of our study. They are commonly found in the central Italian Apennines and the Mediterranean basin. Phytochemicals contained in wild plants, such as phenols, polyphenols, flavonoids, condensed tannins, carotenoids, etc., are receiving increasing attention, as they exert a wide range of biological activities with resulting benefits for human health. Based on the 353 studies we reviewed, we focused our study on the following: (a) the ethnobotanical practices and bioactive phytochemicals; (b) the composition of polyphenols and their role as antioxidants; (c) the methodologies commonly used to assess antioxidant activity; (d) the most advanced spectroscopic and spectrometric techniques used to visualize and characterize all components (metabolomic fingerprinting). The potential of pure compounds and extracts to be used as nutraceuticals has also been highlighted through a supposed mechanism of action. Full article

Functional food factors can play a preventive and therapeutic role in several human diseases. The marine alga Sargassum horneri (S. horneri) has restorative effects in several types of metabolic disorders, including osteoporosis, diabetes, inflammatory conditions, and cancer cell growth. Osteoporosis is widely recognized as a major public health problem. Bone loss associated with ageing and diabetic states was prevented through the intake of bioactive compounds from S. horneri water extract in vivo by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption in vitro. The intake of S. horneri water extract was found to have preventive effects on diabetic findings with an increase in serum glucose and lipid components. Furthermore, the S. horneri component has been shown to suppress adipogenesis from rat bone marrow cells and inflammatory conditions in vitro. Notably, the growth of bone metastatic human breast cancer MDA-MB-231 cells, which induce bone loss with osteolytic effects, was suppressed through culturing with the S. horneri water extract component in vitro. The S. horneri component, which has a molecular weight of less than 1000, was found to suppress the activation of NF-κB signaling by tumor necrosis factor-α, a cytokine associated with inflammation, in osteoblastic cells and macrophage RAW264.7 cells in vitro, suggesting a molecular mechanism. The bioactive component of S. horneri may play a multifunctional role in the prevention and treatment of metabolic disorders. This review outlines the advanced knowledge of the biological activity of the aqueous extract components of S. horneri and discusses the development of health supplements using this material. Full article

Neuroinflammation plays a crucial role in the development of various neurological diseases, including neurodegenerative disorders, leading to significant neuronal dysfunction. Current treatments involve the use of non-steroidal anti-inflammatory drugs and steroids; however, they are associated with serious adverse effects, limiting their efficacy. Exploring natural products with anti-inflammatory properties appears promising, with resveratrol, a polyphenol found in various plants, standing out for its potential benefits. Studies on resveratrol and its anti-inflammatory properties have been increasing in recent years, and analyzing the profile of this knowledge area can bring benefits to the scientific community. Therefore, this study conducted bibliometric analyses, using “resveratrol AND neuroinflammation” as search terms in the Web of Science Core Collection database. The analysis, performed with VOSviewer software version 1.6.18, encompasses 323 publications. Key terms in the studies include “resveratrol”, “neuroinflammation”, and “oxidative stress”, with China leading in the number of publications. The Federal University of Rio Grande do Sul in Brazil emerges as the institution with the highest contribution, and a phase 2 clinical study on resveratrol was the most cited. These results provide an overview of the global research landscape related to resveratrol and neuroinflammation, aiding decision making for future publications and advancing scientific understanding in this field. Full article

The phytonutraceutical Ormona^® is a product composed of purified oil of Bixa orellana Linné, dry extract of Myrciaria dubia McVaugh, dry extract of Trifolium pratense L., and dry extract of Euterpe oleracea Mart. obtained using Evolve^® technology. This study evaluated the effects of Ormona^® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of five groups (n = 5): OVW: treated with distilled water (1 mL/kg, p.o); ADS: alendronate sodium (4 mg/kg p.o); EST: conjugated estrogen (2 µg/kg, p.o); ORM: Ormona^® (20 mg/kg, p.o); ORM + EST: Ormona^® (20 mg/kg, p.o) + conjugated estrogen (2 µg/kg, p.o). Biochemical and hormonal parameters of bone histopathology and trabecular and femoral diaphysis size were evaluated through scanning electron microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca²⁺ concentration. However, Ormona^® showed higher serum estradiol levels (p < 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona^®, therefore, produced better results than the groups treated with estrogen and alendronate sodium. Full article

The immune system plays a crucial role in defending the body against foreign invaders, and the balance of various polyunsaturated fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), can impact immune cell functions and overall immune responses. This study aimed to assess the effectiveness of mussel oil extracts in modulating inflammatory responses by analysing their effects on immune cell lines and cytokine expression. Four different mussel oil extracts were obtained using two extraction methods (organic solvent and supercritical CO₂ extraction) from two tissue sources (fresh and commercial). These extracts were then tested at various concentrations on T lymphocyte (Jurkat) cells, monocytes, and macrophages (THP-1 and U-937). Cytokine levels were quantified using ELISA. The results showed that the solvent-extracted samples had a dose-dependent effect on tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) cytokine secretion in THP-1 and U937 cells, with the extract from a commercial mussel powder being more efficient than the extract from fresh powder. However, supercritical CO₂ samples showed elevated cytokine secretion levels despite their high omega-3 content. Furthermore, 100 ug/mL extract from fresh powder successfully reduced interleukin-2 (IL-2) secretion while maintaining cell viability after stimulation. The study demonstrated that solvent-extracted mussel oil can effectively regulate cytokine secretion, modulate immune cell activation, and alleviate inflammation. These findings offer valuable insights into using mussel oil extracts to treat inflammatory disorders and enhance immune responses. Full article