Nutraceuticals

Rheumatoid arthritis is an autoimmune pathology that follows a chronic course characterized by the involvement of the synovial membrane of joints all over the body. Clinically, the disease is characterized by persistent and painful immune-mediated inflammation, which culminates in bone deformations and joint movement limitation. Alternative therapies, such as garlic, ginger, curcumin, and resveratrol, are beneficial given their anti-inflammatory properties. These alternative therapies are a secondary option for treating the clinical manifestations of rheumatoid arthritis, helping to improve the patient’s quality of life further and preventing future complications. Full article

The bioavailability of vitamin C, or ascorbic acid, depends on limiting transport mechanisms that may be bypassed by liposome-encapsulation. The goal for this study was to evaluate the uptake, antioxidant, and immune-modulating effects of liposome-encapsulated vitamin C (LEC) using Lypo-Spheric^® technology, compared to three controls: ascorbic acid (AA), the phospholipid fraction composing the liposome, and placebo. A double-blinded placebo-controlled cross-over study design involved twelve healthy participants attending four clinic visits. At each visit, a baseline blood draw was performed, followed by consumption of 1 g LEC, 1 g AA, the phospholipid component of LEC, or placebo. Additional blood draws were performed at 2, 4, and 6 h. Consuming LEC and AA increased blood levels of vitamin C; the levels were significantly higher after consuming LEC at all timepoints when compared to AA (p < 0.01). LEC consumption increased serum antioxidant capacity (p < 0.01 at 2 h) and protection. Consuming LEC increased IFN-γ levels at 6 h, while consuming the phospholipid fraction rapidly decreased inflammatory cytokines IL-6, MCP-1, and MIP-1α at 2 h. Consuming LEC provided enhanced vitamin C bioavailability and antioxidant protection compared to AA. Consuming the phospholipids had anti-inflammatory effects. The results suggest that LEC provides antioxidant and immune benefits above AA, useful in preventive medicine. Full article

The purpose of this study was to determine whether a combined L-arginine and L-citrulline beverage can enhance total nitric oxide (NOx), as well as physiological (cardiopulmonary metrics) and perceptual (rate of perceived exertion) responses to a repeated bout of high-intensity exercise among university soccer players. Thirty male soccer players were included in a randomized double-blind, placebo-controlled, parallel design. Participants performed two bouts of high-intensity running, spaced two hours apart. Forty minutes before the second bout only, participants consumed a 500 mL beverage containing 6 g L-arginine and 6 g L-citrulline (n = 15) or placebo (n = 15). Blood NOx concentration was measured immediately before and after both bouts. There was no significant increase in NOx or significant interaction effects for physiological, performance, or perceptual variables between the L-arginine/L-citrulline and placebo groups. The peak volume of oxygen uptake of the L-arginine/L-citrulline group was significantly higher in the second compared with the first exercise bout (54.92 ± 4.81 vs. 50.54 ± 9.22 mL/kg/min; p = 0.01). In the second bout of exercise, time to exhaustion in the L-arginine/L-citrulline group increased by 8.5% (~60 s) compared to the first. In conclusion, these results suggest that a single dose of L-arginine/L-citrulline beverage did not increase NOx yet seemed to impact aerobic metabolism in university soccer players. Full article

There is increasing interest in Australian finger lime (Citrus australasica) due to its nutritional and bioactive potential. In this study, polar extracts from five finger lime cultivars were investigated for their potential bioactivity using a range of assays: antioxidant capacity (total phenolic content (TPC), ferric reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC)), total monomeric anthocyanin content (TMAC), anti-diabetic activity (α-glucosidase and α-amylase inhibition), anti-Alzheimer activity (acetylcholinesterase inhibition), Skin-whitening activity skin-brightening activity (tyrosinase inhibition), and anti-inflammatory activity (COX-2 inhibition). Commercial Tahitian lime was used as a “control” (comparison). The TPC ranged from 328 to 779 mg GAE/100 g dry weight (DW) in the pulp (compared to 1043 mg GAE/100 g for Tahitian lime) and from 755 to 1048 mg GAE/100 g in the peel (1704 mg GAE/100 g for Tahitian lime). A similar range of variation was seen for FRAP, ranging from 114 to 436 mg TE/100 g DW in the pulp (422 mg TE/100 g for Tahitian lime) and 259 to 495 mg TE/100 g DW in the peel (491 mg TE/100 g for Tahitian lime). Similarly, the TFC was generally lower in finger lime pulp (100–392 mg QE/100 g DW) compared to Tahitian lime (312 mg QE/100 g). The polar extracts did not show any significant inhibition of α-glucosidase, α-amylase, tyrosinase, or COX-2. One finger lime variety showed moderate (>50%) inhibition of acetylcholinesterase (AChE) at the highest concentration screened (~1500 mg/L), as did Tahitian lime. Additionally, in silico docking against acetylcholinesterase suggested that some of the polyphenols present, including catechin, quercetin-3-glucoside, and cyanidin-3-glucoside, could potentially dock to AChE and inhibit it. This is the first time the species has been investigated for many of these bioactive properties, and also the first time in silico docking has been performed to explore which potential compounds from this species could provide its bioactivity. Although little bioactivity was generally found across the applied bioassays, these findings nevertheless provide important basic data for future research and any claims about the potential health benefits of Australian finger lime. Full article

The major constituent of turmeric, curcumin, is a bioactive phenolic compound that has been studied for its potential health benefits and therapeutic properties. Within this article, the anti-inflammatory, antioxidant and antithrombotic properties and mechanisms of action of curcumin are thoroughly reviewed and the main focus is shifted to its associated health-promoting effects against inflammation-related chronic disorders. An overview of the cardio-protective, anti-tumor, anti-diabetic, anti-obesity, anti-microbial and neuro–protective health-promoting properties of curcumin are thoroughly reviewed, while relative outcomes obtained from clinical trials are also presented. Emphasis is given to the wound-healing properties of curcumin, as presented by several studies and clinical trials, which further promote the application of curcumin as a bioactive ingredient in several functional products, including functional foods, nutraceuticals, cosmetics and drugs. Limitations and future perspectives of such uses of curcumin as a bio-functional ingredient are also discussed. Full article

Inflammation and thrombosis are implicated in several non-communicable chronic disorders, including cardiovascular diseases, diabetes, renal and neurodegenerative disorders, skin diseases, and especially in cancer. Natural bioactives and especially phytochemicals like phenolic compounds have been proposed to reduce the inflammatory burden with several health benefits against these disorders. Vanillin is a phenolic compound found in the seeds of various species of vanilla plants. It has been known since ancient times for its aromatic and soothing properties; however, recent outcomes have outlined several other pleiotropic actions for this phenolic bioactive compound. Within this article, the potent anti-inflammatory activities of vanillin and its derivatives are thoroughly reviewed, with emphasis on their anti-cancer, anti-infective, wound-healing, and neuroprotective health-promoting properties. The mechanisms of their action(s), along with recent outcomes from in vitro and in vivo studies and clinical trials, on the benefits of these vanillin-based phenolic bioactives against each of these disorders, and especially against specific types of cancer, are also outlined. Limitations and future perspectives of their use solely as bioactive ingredients, as ingredients in several functional products—such as functional foods, supplements, nutraceuticals, or even cosmetics and drugs—and even as adjuvant therapies are also discussed. Full article

The increasing protein demand driven by global population growth necessitates the search for an alternative protein source. Soybean meal (SM), with approximately 47–49% proteins, is a viable option. Soymeal protein isolate (SMPI) is a cost-efficient protein source with a well-balanced amino acid profile, making it suitable for addressing this demand. This study attempts to address the lack of information regarding the extractability and nutritional potential of SMPI obtained utilizing a weak base and recoverable solvent. In this work, the structural and compositional studies of SMPI, as well as the aqueous extractability of ammonium hydroxide (NH₄OH), are investigated. Furthermore, we examined the effects of heat treatment during oil extraction, where a comparison between protein isolates from soymeal and whole soybeans was carried out. The maximum extraction yield of 24.1% was achieved by increasing the concentration of NH₄OH from 0.25–1%. In comparison to the soy protein isolate from whole soybeans (SPI), the compositional analysis report revealed that SMPI had higher levels of crude protein, moisture, and ash content, but lower levels of fat and carbohydrates. Furthermore, the examination of the amino acid composition confirms the existence of vital amino acids in SMPI. The amino acid score indicates that methionine, lysine, and threonine are the limiting amino acids. SMPI and SPI share structural and functional group similarities, as demonstrated by Fourier-transform infrared spectroscopy. Gel electrophoresis using sodium dodecyl sulfate–polyacrylamide shows that the protein molecular weight distributions of SPI and SMPI are similar. This in-depth evaluation emphasizes the advantages of SM by advocating its application in other sectors beyond conventional animal feed, such as nutritional supplements and bio-based products, and by improving the environmental sustainability and global food chains. Full article

High-density lipoprotein (HDL) has been proposed to provide cardio-protective properties through the functionality of its anti-inflammatory and antioxidant enzymatic machinery. Within this article, the beneficial effects of several functional foods on HDL levels and functionality for cardio-protection are thoroughly reviewed. Emphasis is given to functional foods and their antioxidant and anti-inflammatory health-promoting effects for the cardiovascular system through their benefits on HDL, which act either solely or synergistically as an adjuvant approach with well-established anti-atherogenic therapies. Promising outcomes from both in vitro and in vivo studies in animal models and clinical trials, which outline the beneficial effects of such functional foods on HDL levels and functionality, are thoroughly discussed. The mechanisms of the obtained antioxidant, anti-inflammatory, antithrombotic, and cardio-protective effects on HDL activities of functional foods containing natural bioactives are also outlined. Limitations and future perspectives on the overall benefits that these natural bioactive compounds exert as important ingredients in functional foods to induce HDL-related benefits and to strengthen cardiovascular health are also discussed. Full article

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