ABSTRACT
Vegetarian diets are plant-based diets including all the edible foods from the Plant Kingdom, such as grains, legumes, vegetables, fruits, nuts, and seeds. Dairy and eggs can be added in small amounts in the lacto-ovo-vegetarian subtype, or not at all in the vegan subtype. The abundance of non-processed plant foods-typical of all well-planned diets, including vegetarian ones-can provide the body with numerous protective factors (fiber, phytocompounds), while limiting the intake of harmful nutrients like saturated fats, heme-iron, and cholesterol. The beneficial effects on health of this balance have been reported for many main chronic diseases, in both observational and intervention studies. The scientific literature indicates that vegetarians have a lower risk of certain types of cancer, overall cancer, overweight-obesity, type 2 diabetes, dyslipidemia, hypertension, and vascular diseases. Since the trend of following a vegetarian diet is increasing among citizens of developed countries, the knowledge in the field will benefit from further studies confirming the consistency of these findings and clarifying the effects of vegetarian diets on other controversial topics.
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Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest for their possible health benefits. In this review, we summarized the results of clinical studies on vascular outcomes of flavan-3-ol supplementation and we focused on the role of the microbiota in CVD. Clinical trials included in this review showed that supplementation with flavan-3-ols mostly derived from cocoa products significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals. From a mechanistic point of view, emerging evidence suggests that microbial metabolites may play a role in the observed effects. Their function extends beyond the previous belief of ROS scavenging activity and encompasses a direct impact on gene expression and protein function. Although flavan-3-ols appear to have effects on cardiovascular health, further studies are needed to clarify and confirm these potential benefits and the rising evidence of the potential involvement of the microbiota.
Subject(s)
Cardiovascular Diseases , Flavonoids , Humans , Flavonoids/pharmacology , Cardiovascular Diseases/prevention & control , Cacao/chemistry , Tea/chemistry , Dietary Supplements , Blood Pressure/drug effects , Endothelium, Vascular/drug effectsABSTRACT
In the last decades, the world population and demand for any kind of product have grown exponentially. The rhythm of production to satisfy the request of the population has become unsustainable and the concept of the linear economy, introduced after the Industrial Revolution, has been replaced by a new economic approach, the circular economy. In this new economic model, the concept of "the end of life" is substituted by the concept of restoration, providing a new life to many industrial wastes. Leaves are a by-product of several agricultural cultivations. In recent years, the scientific interest regarding leaf biochemical composition grew, recording that plant leaves may be considered an alternative source of bioactive substances. Plant leaves' main bioactive compounds are similar to those in fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. Bioactive compounds can positively influence human health; in fact, it is no coincidence that the leaves were used by our ancestors as a natural remedy for various pathological conditions. Therefore, leaves can be exploited to manufacture many products in food (e.g., being incorporated in food formulations as natural antioxidants, or used to create edible coatings or films for food packaging), cosmetic and pharmaceutical industries (e.g., promising ingredients in anti-aging cosmetics such as oils, serums, dermatological creams, bath gels, and other products). This review focuses on the leaves' main bioactive compounds and their beneficial health effects, indicating their applications until today to enhance them as a harvesting by-product and highlight their possible reuse for new potential healthy products.
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Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.
Subject(s)
Colonic Neoplasms , Epithelial-Mesenchymal Transition , Honey , Neoplastic Stem Cells , Neovascularization, Pathologic , Epithelial-Mesenchymal Transition/drug effects , Humans , Neoplastic Stem Cells/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Neovascularization, Pathologic/drug therapy , Cell Line, Tumor , Snail Family Transcription Factors/metabolism , Snail Family Transcription Factors/genetics , Fluorouracil/pharmacology , Leptospermum/chemistry , Cell Movement/drug effects , Neoplasm Metastasis , Telomere/drug effects , Telomere Homeostasis/drug effects , AngiogenesisABSTRACT
Although recent evidence indicated significant phenol and alkylamide interaction in aqueous solutions, the gastrointestinal digestion influence of the combination remains unclear. This study aims to investigate phenol and alkylamide interaction during in vitro digestion, focusing on bioaccessibility and bioactivity, including α-glucosidase inhibition and cellular antioxidant activity. Additionally, the structural mechanism of phenol and alkylamide interaction during in vitro digestion was explored. The results indicated that the presence of phenols and alkylamides significantly increased or decreased their respective bioaccessibility, depending on the Zanthoxylum varieties. Furthermore, although antagonistic phenol/alkylamide interaction was evident during α-glucosidase inhibition, cellular oxidative stress alleviation, and antioxidant gene transcription upregulation, this effect weakened gradually as digestion progressed. Glycoside bond cleavage and the methylation of phenols as well as alkylamide isomerization and addition were observed during digestion, modifying the hydrogen bonding sites and interaction behavior. This study provided insights into the phenol/alkylamide interaction in the gastrointestinal tract.
Subject(s)
Amides , Antioxidants , Digestion , Glycoside Hydrolase Inhibitors , Plant Extracts , Zanthoxylum , alpha-Glucosidases , Zanthoxylum/chemistry , Zanthoxylum/metabolism , Antioxidants/chemistry , Antioxidants/metabolism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/metabolism , alpha-Glucosidases/chemistry , alpha-Glucosidases/genetics , Humans , Amides/chemistry , Amides/metabolism , Amides/pharmacology , Plant Extracts/chemistry , Plant Extracts/metabolism , Plant Extracts/pharmacology , Phenols/chemistry , Phenols/metabolism , Models, Biological , Phenol/metabolism , Phenol/chemistryABSTRACT
Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.
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Over the last decades, the Mediterranean diet gained enormous scientific, social, and commercial attention due to proven positive effects on health and undeniable taste that facilitated a widespread popularity. Researchers have investigated the role of Mediterranean-type dietary patterns on human health all around the world, reporting consistent findings concerning its benefits. However, what does truly define the Mediterranean diet? The myriad of dietary scores synthesizes the nutritional content of a Mediterranean-type diet, but a variety of aspects are generally unexplored when studying the adherence to this dietary pattern. Among dietary factors, the main characteristics of the Mediterranean diet, such as consumption of fruit and vegetables, olive oil, and cereals should be accompanied by other underrated features, such as the following: (i) specific reference to whole-grain consumption; (ii) considering the consumption of legumes, nuts, seeds, herbs and spices often untested when exploring the adherence to the Mediterranean diet; (iii) consumption of eggs and dairy products as common foods consumed in the Mediterranean region (irrespectively of the modern demonization of dietary fat intake). Another main feature of the Mediterranean diet includes (red) wine consumption, but more general patterns of alcohol intake are generally unmeasured, lacking specificity concerning the drinking occasion and intensity (i.e., alcohol drinking during meals). Among other underrated aspects, cooking methods are rather simple and yet extremely varied. Several underrated aspects are related to the quality of food consumed when the Mediterranean diet was first investigated: foods are locally produced, minimally processed, and preserved with more natural methods (i.e., fermentation), strongly connected with the territory with limited and controlled impact on the environment. Dietary habits are also associated with lifestyle behaviors, such as sleeping patterns, and social and cultural values, favoring commensality and frugality. In conclusion, it is rather reductive to consider the Mediterranean diet as just a pattern of food groups to be consumed decontextualized from the social and geographical background of Mediterranean culture. While the methodologies to study the Mediterranean diet have demonstrated to be useful up to date, a more holistic approach should be considered in future studies by considering the aforementioned underrated features and values to be potentially applied globally through the concept of a "Planeterranean" diet.
Subject(s)
Diet, Mediterranean , Humans , Diet , Feeding Behavior , Olive Oil , Spices , Life StyleABSTRACT
Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-ß- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.
Subject(s)
Alzheimer Disease , Brassica , Caenorhabditis elegans Proteins , Animals , Antioxidants/metabolism , Oxidative Stress , Caenorhabditis elegans Proteins/metabolism , Brassica/metabolism , Acetylcholinesterase , Plant Extracts/pharmacology , Aging , Caenorhabditis elegans , Reactive Oxygen Species , Oxidation-Reduction , Longevity , BiologyABSTRACT
In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.
Subject(s)
Antioxidants , Iridoid Glucosides , Olea , Phenylethyl Alcohol/analogs & derivatives , Antioxidants/chemistry , Acetylcholinesterase , Olea/chemistry , Cyclooxygenase 2 , Plant Extracts/chemistry , Iridoids/analysis , Phytochemicals/analysis , Plant Leaves/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/analysis , Cholinergic Antagonists/analysisABSTRACT
Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol-a microbiota-derived metabolite-seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.
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Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.
Subject(s)
Atherosclerosis , Carotid Intima-Media Thickness , Humans , Pulse Wave Analysis , Cross-Sectional Studies , Healthy Volunteers , Risk Factors , Vegetarians , Diet, VegetarianABSTRACT
Correction for 'Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis' by Alicia Saz-Lara et al., Food Funct., 2024, https://doi.org/10.1039/D3FO05061K.
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The development of an analytical method for assessing pungency intensity and determining geographical origins is crucial for evaluating the quality of visually similar Zanthoxylum bungeanum pericarp (PZB). This study analyzed 210 PZB samples from 14 origins across China, focusing on origin adulteration identification and pungency intensity using a combination of differential pulse voltammetry (DPV) and machine learning algorithms. The artificial neural network (ANN) and K-nearest neighbor (KNN) algorithms provided the highest accuracy in origin identification (100 %) and adulteration detection (97.9 %) respectively. Moreover, the ANN excelled in predicting pungency intensity (R2 = 0.918). Assessment via feature importance analysis of DPV features revealed that segments of polyphenols (0.34-0.52 V and 1.0-1.2 V) and alkylamides (1.0-1.2 V) contributed significantly to the PZB pungency intensity. These findings highlight the potential of DPV as a reliable method for assessing the quality of PZB, and offer a promising solution for ensuring the geographical authenticity of this important crop.
Subject(s)
Capsicum , Zanthoxylum , Algorithms , Neural Networks, Computer , Machine LearningABSTRACT
Twenty years after its discovery, hepcidin is still considered the main regulator of iron homeostasis in humans. The increase in hepcidin expression drastically blocks the flow of iron, which can come from one's diet, from iron stores, and from erythrophagocytosis. Many anemic conditions are caused by non-physiologic increases in hepcidin. The sequestration of iron in the intestine and in other tissues poses worrying premises in view of discoveries about the mechanisms of ferroptosis. The nutritional treatment of these anemic states cannot ignore the nutritional modulation of hepcidin, in addition to the bioavailability of iron. This work aims to describe and summarize the few findings about the role of hepcidin in anemic diseases and ferroptosis, as well as the modulation of hepcidin levels by diet and nutrients.
Subject(s)
Anemia , Hepcidins , Humans , Hepcidins/metabolism , Anemia/etiology , Iron/metabolismABSTRACT
Epidemiological studies have shown that eating fish significantly reduces cardiovascular disease (CVD) incidence and mortality. However, more focused meta-analyses based on the most recent results from prospective cohort studies are needed. This systematic review and meta-analysis aims to update the association between fish intake and cardiovascular disease (CVD) risk using recent prospective studies. A systematic review and meta-analysis following the PRISMA guideline was conducted based on a random effects synthesis of multivariable-adjusted relative risks (RRs) of high vs. low categories of fish intake in relation to CVD incidence and mortality. Non-linear meta-regression was applied to investigate the shape of the association between fish intake and CVD risk. Sensitivity analysis and stratifications by type of CVD outcome, type of fish intake and type of cooking were performed. Based on 18 papers reporting 17 independent estimates of CVD risk (1,442,407 participants and 78,805 fatal and non-fatal CVD events), high vs. low intake of fish corresponded to about 8% reduced CVD risk (RR = 0.93 [0.88-0.98]). According to a non-linear dose-response meta-regression, 50 g of fish intake per day corresponded to a statistically significant 9% reduced fatal and non-fatal CVD risk (RR = 0.92 [0.90-0.95]). Similarly, fish intake in the range of a weekly intake of two to three portions of fish with a size of 150 g resulted in 8% fatal and non-fatal CVD risk reduction (RR = 0.93 [0.91-0.96]). The recommended two portions of fish a week reduces the risk of CVD outcomes by approximately 10%. A full portion of fish a day reduces CVD risk by up to 30%.
Subject(s)
Cardiovascular Diseases , Animals , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Prospective Studies , Risk Factors , Cohort Studies , IncidenceABSTRACT
The health concerns associated with high dietary sodium and the quest for a sensory experience have prompted the need for new strategies that can reduce the salt content of foods and have good acceptability. To investigate the cross-modal interaction effects of "má là" umami flavor (total of eight carriers) on the saltiness perception and effective sodium reduction in low-to-strong NaCl aqueous solutions (0.203 %-1.39 %) and oil-added systems (5 %, 10 %, 15 %, 20 %, 25 % canola oil, wt%), sixteen assessors were selected and two methods including saltiness intensity comparison with a category scale and rating with a generalized Labeled Magnitude Scale (gLMS) were used. The results showed PnSnUn carriers significantly enhance saltiness at moderate-to-strong NaCl solutions, and higher saltiness intensity with the addition of canola oil, especially at 25 % oil level. In addition, based on the developed Stevens' power function the sodium reduction was calculated, it was evident that two "má là" umami flavor combinations (one flavor combination was low "má", low "là" and moderate umami, and the other flavor combination with moderate "má", low "là" and moderate umami) were found to perform best with maximum sodium reduction of 18.88 % and 18 %, respectively, and when incorporating 25 % canola oil, the maximum sodium reduction raised by approximately 10 % (to 28.00 % and 28.42 %). This research not only confirmed the positive modulating effect of the "má là" umami flavor on saltiness perception in NaCl solutions, but also showed that the presence of oil further enhanced this effect. This work offered a new and promising insight into the development of foods with reduced sodium content while maintaining the saltiness properties.
Subject(s)
Sodium Chloride , Taste , Sodium Chloride/pharmacology , Rapeseed Oil , Sodium Chloride, Dietary , Water , SodiumABSTRACT
Diabetes is a metabolic disease due to impaired or defective insulin secretion and is considered one of the most serious chronic diseases worldwide. Gamma-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid commonly present in a wide range of foods. A number of studies documented that GABA has good anti-diabetic potential. This review summarized the available dietary sources of GABA as well as animal and human studies on the anti-diabetic properties of GABA, while also discussing the underlying mechanisms. GABA may modulate diabetes through various pathways such as inhibiting the activities of α-amylase and α-glucosidase, promoting ß-cell proliferation, stimulating insulin secretion from ß-cells, inhibiting glucagon secretion from α-cells, improving insulin resistance and glucose tolerance, and increasing antioxidant and anti-inflammatory activities. However, further mechanistic studies on animals and human are needed to confirm the therapeutic effects of GABA against diabetes.
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The leaves of the olive tree (Olea europaea L.) are one of the major solid wastes from the olive industry. Globally, the European Union is the largest producer of olive by-products, with Spain, Italy, Greece, and Portugal accounting for almost the entire production. Many questions remain to be solved concerning olive leaves (OL), including those related to possible differences in composition and/or biological activities depending on their geographical origin. In the present work, OL from Spain, Italy, Greece, and Portugal have been characterized according to their phytochemical profile, antioxidant capacity, neuroprotective activity, and anti-inflammatory effects. The Spanish and Italian OL samples presented the highest antioxidant and neuroprotective activities, while the Greek OL showed the lowest. These results were strongly associated with the content of oleoside methyl ester and p-hydroxybenzoic acid for the Spanish and Italian samples, respectively, whereas the content of decarboxymethyl elenolic acid dialdehyde form (hydrated) was negatively associated with the mentioned biological activities of the Greek samples. No country-related effect was observed in the anti-inflammatory activity of OL. Comprehensively, this work could provide a useful tool for manufacturers and R&D departments in making environmentally friendly decisions on how OL can be used to generate nutraceutical products based on the composition and origin of this by-product.
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Asparagus species is recognized as a perennial herb with several valuable functional ingredients, and has been widely used as medicine and food since ancient times. Among its main chemical constituents, saponins play a vital role in the health benefits and biological activities including anti-cancer, antioxidant, immunomodulatory, anti-microbial, anti-inflammatory, and hypoglycemic. This review summarizes the preparation methods, structure and classification, biological functions, as well as the food and non-food applications of asparagus saponins, with a special emphasis on its anti-cancer effects in vitro and in vivo. Further, the main challenges and limitations of the current research trends in asparagus saponins are highlighted after a detailed analysis of the recent research information. This review bridges the gap between bioactive components and human health and aids current research on functional and health-promoting foods and medicinal application of Asparagus saponins.
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Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/ß-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects.