Saffron against Neuro-Cognitive Disorders: An Overview of Its Main Bioactive Compounds,Their Metabolic Fate and Potential Mechanisms of Neurological Protection

Saffron (Crocus sativus L.) is a spice used worldwide as a colouring and flavouring agent. Saffron is also a source of multiple bioactive constituents with potential health benefits. Notably, saffron displays consistent beneficial effects against a range of human neurological disorders (depression, anxiety, sleeping alterations). However, the specific compounds and biological mechanisms by which this protection may be achieved have not yet been elucidated. In this review, we have gathered the most updated evidence of the neurological benefits of saffron, as well as the current knowledge on the main saffron constituents, their bioavailability and the potential biological routes and postulated mechanisms by which the beneficial protective effect may occur. Our aim was to provide an overview of the neuroprotective effects attributed to this product and its main bioactive compounds and to highlight the main research gaps that need to be further pursued to achieve full evidence and understanding of the benefits of saffron. Overall, improved clinical trials and adequately designed pre-clinical studies are needed to support the evidence of saffron and of its main bioactive components (e.g., crocin, crocetin) as a therapeutic product to combat neurological disorders.     

Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases

Fructus lycii (F. lycii) is an exotic “berry-type” fruit of the plant Lycium barbarum that is characterized by a complex mixture of bioactive compounds distinguished by their high antioxidant potential. F. lycii is used in traditional Chinese home cooking and in the Chinese Pharmacopeia as an aid to vision and longevity as well as a remedy for diabetes to balance “yin” and “yang” in the body for about two centuries. Although a myriad of bioactive compounds have been isolated from F. lycii, polysaccharides, carotenoids, flavonoids, and phenolics represent the key functional components of F. lycii. F. lycii has been shown to exhibit a wide range of biological activities in experimental settings including antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects. Despite its medicinal role dating back to the eighteenth century in the Far East and robust evidence of beneficial effects on ocular health and retinal diseases originating mainly from studies in animal models, the role of F. lycii in the clinical management of retinal diseases is yet to be established. This article comprehensively reviews the literature germane to F. lycii and retinal diseases with particular emphasis on age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa, which are commonly seen in clinical practice.     

Saffron Extract-Induced Improvement of Depressive-Like Behavior in Mice Is Associated with Modulation of Monoaminergic Neurotransmission

Depressive disorders represent a major public health concern and display a continuously rising prevalence. Importantly, a large proportion of patients develops aversive side effects and/or does not respond properly to conventional antidepressants. These issues highlight the need to identify further therapeutic strategies, including nutritional approaches using natural plant extracts with known beneficial impacts on health. In that context, growing evidence suggests that saffron could be a particularly promising candidate. This preclinical study aimed therefore to test its antidepressant-like properties in mice and to decipher the underlying mechanisms by focusing on monoaminergic neurotransmission, due to its strong implication in mood disorders. For this purpose, the behavioral and neurobiochemical impact of a saffron extract, Safr’Inside™ (6.5 mg/kg per os) was measured in naïve mice. Saffron extract reduced depressive-like behavior in the forced swim test. This behavioral improvement was associated with neurobiological modifications, particularly changes in serotonergic and dopaminergic neurotransmission, suggesting that Safr’Inside™ may share common targets with conventional pharmacological antidepressants. This study provides useful information on the therapeutic relevance of nutritional interventions with saffron extracts to improve management of mood disorders.     

Interactive effects of saffron with garlic and curcumin against cyclophosphamide induced genotoxicity in mice

Saffron is a well-known spice and food colorant commonly consumed in different parts of the world. Recently, much attention has been focused on the biological and medicinal properties of saffron. In the present study the interactive effects of saffron with two commonly consumed dietary agents, garlic and curcumin was evaluated for anti-genotoxic effects against cyclophosphamide (CPH) in the mouse bone marrow micronucleus test. Experimental animals were orally pretreated with saffron (100 mg/kg body weight), garlic (250 mg/kg body weight) and curcumin (10 mg/kg body weight), either alone or in combination for five consecutive days, 2h prior to the administration of CPH. Maximum reduction in the frequencies of micronucleated polychromatic erythrocytes (Mn PCEs) induced by CPH was observed when all the three test compounds were administered together. Furthermore, the protective effects were more pronounced in the garlic-administered groups compared to curcumin and/or saffron administered groups.     

Role of Antioxidant Lycopene in Cancer and Heart Disease

Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables; however, tomatoes and processed tomato products constitute the major source of lycopene in North American diet. Among the carotenoids, lycopene is a major component found in the serum and other tissues. Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in several recent studies. Serum and tissue lycopene levels have also been inversely related with the chronic disease risk. Although the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial properties, evidence is accumulating to suggest other mechanisms such as modulation of intercellular gap junction communication, hormonal and immune system and metabolic pathways may also be involved. This review summarizes the background information about lycopene and presents the most current knowledge with respect to its role in human health and disease.     

The Effect of Saffron Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials

Background: The favorable influences of saffron supplementation on metabolic diseases have previously been shown. We aimed to assess the effects of saffron supplementation on blood pressure in adults. Methods: A systematic search was performed in Scopus, Embase, and the Cochrane library databases to find randomized controlled trials (RCTs) related to the effect of saffron supplementation on blood pressure in adults up to March 2021. The primary search yielded 182 publications, of which eight RCTs were eligible. Results: Our results showed that saffron supplementation resulted in a significant decrease in systolic blood pressure (weighted mean difference (WMD): −0.65 mmHg; 95% CI: −1.12 to −0.18, p = 0.006) and diastolic blood pressure (DBP) (WMD: −1.23 mmHg; 95% CI: −1.64 to −0.81, p < 0.001). Moreover, saffron supplementation reduced DBP in a non-linear fashion, based on duration (r = −2.45, p-nonlinearity = 0.008). Conclusions: Saffron supplementation may significantly improve both systolic and diastolic blood pressure in adults. It should be noted that the hypotensive effects of saffron supplementation were small and may not reach clinical importance.     

Inhibitory effects of aqueous crude extract of Saffron (Crocus sativus L.) on chemical-induced genotoxicity in mice

Saffron (dried stigmas of Crocus sativus L.), was evaluated in the mouse bone marrow micronucleus test for its possible protective effects against chromosomal damage induced by cisplatin (CIS), mitomycin-C (MMC) and urethane (URE). Three doses of saffron (25, 50 and 100 mg/kg body weight) were orally administered to mice for five consecutive days prior to administration of genotoxins under investigation. From the results obtained, it was evident that the administration of 50 and 100 mg saffron/kg body weight could significantly inhibit the in vivo genotoxicity of these genotoxins. However, all the three doses of saffron were effective in exerting a protective effect against urethane.     

Influence of corm provenance and environmental condition on yield and apocarotenoid profiles in saffron (Crocus sativus L.)

Saffron is well known for its use as a condiment spice, as a dye and in traditional medicine, but very little information is available on the relationship between agronomic management and the qualitative features of this spice, the latter strictly associated with its unique metabolic profile represented by the crocetin esters, picrocrocin and safranal. There is increasing interest in saffron because of its specific and multiple properties. The aim of this study was to evaluate the influence of climatic condition and genotype on compositional characteristics of saffron. Flower number and stigma yield were significantly affected by environment and corm provenance. The content of the main crocetin esters, namely trans-crocetin di-(β-d-gentibiosyl) ester (1), trans-crocetin (β-d-glucosyl)-(β-d-gentibiosyl) ester (2), trans-crocetin (β-d-gentibiosyl) ester (3), trans-crocetin (β-d-glucosyl) ester (4), and picrocrocin, were evaluated according to the spectrophotometric ISO standard methodology, which ranked the samples into three qualitatively decreasing categories (I–III); composition was evaluated mainly through the application of HPLC equipped with ultraviolet visible diode array detector and electro-spray mass spectrometer detectors (HPLC–UV–vis-DAD–ESI-MS), which made it possible to determine the metabolic profiles of stigma samples in terms of crocetin esters and picrocrocin content. The chemical data were combined with the environmental conditions and genotype, and the results showed that crocetin esters 1 and 2 represent the major components of total crocetin ester amount, as indicated by the high positive correlation (0.971 and 0.833, respectively). Moreover crocetin esters 2 and 4, and total crocetin esters amount resulted correlated with picrocrocin content (0.794, 0.818 and 0.678, respectively). Finally, a Pearson correlation was performed in order to individuate any possible relationship between yield characteristics (flower number, total yield and unitary stigma weight) and the qualitative parameters of saffron.     

Lutein and Zeaxanthin and Their Roles in Age-Related Macular Degeneration—Neurodegenerative Disease

Lutein and zeaxanthin belong to the xanthophyll family of carotenoids, which are pigments produced by plants. Structurally, they are very similar, differing only slightly in the arrangement of atoms. Key sources of these carotenoids include kale, savoy cabbage, spinach, broccoli, peas, parsley, corn, and egg yolks. The recommended daily intake of lutein is approximately 10.0 mg and that of zeaxanthin is 2 mg. Lutein intake in adults varies, with average intakes being 1–2 mg/day. Due to the lack of synthesis of consumption of these compounds in humans, these substances are extremely important for the proper functioning of certain organs of the body (eye, skin, heart, intestines). Eating a lot of dark leafy vegetables and some fruits can help to prevent our bodies from developing diseases. The protective effects of carotenoids are mainly related to their defense against oxidative stress and their ability to scavenge free radicals. Lutein and zeaxanthin are the only dietary carotenoids that accumulate in the retina, specifically the macula, and are called macular pigments. These carotenoids are concentrated by the action of specific binding proteins such as StARD3, which binds lutein, and GSTP1, which binds zeaxanthin and its dietary metabolite, mesozeaxanthin. It has been shown that supportive therapy with lutein and zeaxanthin can have a beneficial effect in delaying the progression of eye diseases such as age-related macular degeneration (AMD) and cataracts. This article presents the current state of knowledge on the role of lutein and zeaxanthin, especially from human studies targeting their metabolism and bioavailability, with recommendations to consume xanthophyll-rich foods.     

The Role of Resveratrol in Eye Diseases—A Review of the Literature

Resveratrol (3,5,4′-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.     

Nutritional and clinical relevance of lutein in human health

Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine.     

Role of antioxidant lycopene in cancer and heart disease

Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables; however, tomatoes and processed tomato products constitute the major source of lycopene in North American diet. Among the carotenoids, lycopene is a major component found in the serum and other tissues. Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in several recent studies. Serum and tissue lycopene levels have also been inversely related with the chronic disease risk. Although the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial properties, evidence is accumulating to suggest other mechanisms such as modulation of intercellular gap junction communication, hormonal and immune system and metabolic pathways may also be involved. This review summarizes the background information about lycopene and presents the most current knowledge with respect to its role in human health and disease.     

Hispanic and non-Hispanic white elders from Massachusetts have different patterns of carotenoid intake and plasma concentrations

Carotenoids have been linked with protective roles against diseases associated with aging, including cancer, cardiovascular disease, cataracts, and age-related macular degeneration. With data from a semiquantitative, validated FFQ, we examined carotenoid intake of 340 Puerto Ricans, 98 Dominicans, and 146 non-Hispanic whites (>60 y old) in Massachusetts. Compared with non-Hispanic white men, Hispanic men reported a higher intake of lycopene and lower intakes of alpha-carotene, lutein + zeaxanthin, beta-carotene (from diet only), and total beta-carotene (diet and supplements) (P < 0.001). Hispanic women reported higher intakes of beta-cryptoxanthin and lycopene but lower intakes of lutein + zeaxanthin (P < 0.001) than non-Hispanic white women. The frequency of consumption of fruit and vegetables was higher among Hispanic women, relative to non-Hispanic white women (P < 0.05). Plasma concentrations of alpha-carotene and lycopene were higher in Hispanic than in non-Hispanic white men and women. For both ethnic groups, higher intakes of carotenoids were associated with higher plasma concentrations of the respective carotenoids, except for lycopene (Hispanics) and lutein + zeaxanthin (non-Hispanic whites). Food sources contributing most to total intakes differed among the groups. The major sources of alpha- and beta-carotene were carrots for non-Hispanic whites and winter squash for Hispanics. The major source of lycopene was cooked tomato products for Hispanics, and pasta dishes for non-Hispanic whites. Traditional foods such as beans and plantains were also important contributors of carotenoids for Hispanics. Because of the potential importance of carotenoids as protective factors against chronic diseases, more attention to food-related practices associated with carotenoid intake in differing population groups is warranted.     

Comparison of the postprandial chylomicron carotenoid responses in young and older subjects

Summary. Background: The plant carotenoids may contribute to the beneficial health effect of fruits- and vegetables-rich diet. Epidemiological studies consistently associated high plasma carotenoids status with reduced age-related diseases. However, the data concerning the bioavailability of carotenoids in the elderly are scarce. Objective: To test whether there is an age effect on carotenoid bioavailability. Design: Eight young (20–35 y) and eight older (60–75 y) healthy adults ingested three different meals containing 40 g triacylglycerols (TG) and vegetable sources of carotenoids. These sources were either 188 g carrot purée which provided 30 mg betacarotene as the main carotenoid, or 61 g tomato purée providing 30mg lycopene, or 260 g cooked chopped spinach providing 30 mg lutein. TG and carotenoids were assayed in chylomicrons (CM) collected for 9 h postprandially. Results: There was no major effect of age on the postprandial CM/TG response (0–9 h area under the curve (AUC)). There was no major effect of age on the postprandial CM all-trans beta-carotene, cis betacarotene, alpha-carotene, and lutein responses.Adjustment of these responses by the CM TG responses did not reveal any age effect. While there was no significant effect of age on the CM lycopene response, the CM TG-adjusted lycopene response was significantly lower (–40 %) in the older than in the younger subjects (P < 0.04). The cis-trans ratios of CM betacarotene were not significantly different between the old and the young subjects. There was no significant effect of age on the ratio of CM retinyl-palmitate to the sum of alpha-carotene and beta-carotene measured after the carrot meal. Conclusions: The bioavailability of lycopene is apparently impaired in the old,while there is no major difference in the bioavailability of beta-carotene, alpha-carotene and probably lutein. There is also no major effect of age on the cis-trans isomerization of beta-carotene during absorption, and in the intestinal conversion of provitamin A carotenoids into vitamin A.This study has been carried out with financial support from the Commission of the European Communities, specific RTD program Quality of Life and Management of Living Resources, QLK1-CT-1999–00830. It does not necessarily reflect its views and in no way anticipates the Commissions future policy in this area.     

Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer

In addition to his many research achievements, James Allen Olson made important contributions to evaluations of the role of dietary carotenoids in prevention of chronic diseases such as cancer, heart disease and age-related macular degeneration in well-nourished populations. This paper reviews recent scientific evaluations of the role of carotenoids in disease, recommendations for future research, and consumer-related trends of relevance to carotenoids. Authoritative scientific evaluations by key leading thinkers have not been able to ascribe a disease prevention function to carotenoids because of the absence of definitive evidence. These leading thinkers recommend that future research on the role of carotenoids in disease focus on the complexities of diet, genetics and environment in the disease process. This research is important to make it possible for consumers to derive optimal health promoting benefits from fruits and vegetables in the context of changing dietary patterns.     

Oxidative stress and cognitive impairment in the elderly

Cognitive impairment is a major component of age-related dementing diseases and it has been suggested that it could share the same pathological pathways with neurodegenerative processes and cerebrovascular lesions. The free radical theory of aging could be one of these pathways. Observational studies of relationships between cognitive impairment and antioxidant status are based on the evaluation of dietary intake or on the levels of carotenoids, selenium and vitamins A, C and E in plasma. More convincing results were obtained on vitamin C and carotenoids. Despite some limitations, the comparison between results obtained in various populations is becoming increasingly informative and these studies argue for a protective effect of antioxidants on cognitive performance.     

Anti-Aging and Neuroprotective Properties of Grifola frondosa and Hericium erinaceus Extracts

Nutrition has relevant consequences for human health and increasing pieces of evidence indicate that medicinal mushrooms have several beneficial effects. One of the main issues in Western countries is represented by the challenges of aging and age-related diseases, such as neurodegenerative disorders. Among these, Parkinson’s disease (PD) affects 10 million people worldwide and is associated with α-synuclein misfolding, also found in other pathologies collectively called synucleinopathies. Here, we show that aqueous extracts of two edible mushrooms, Grifola frondosa and Hericium erinaceus, represent a valuable source of β-glucans and exert anti-aging effects in yeast. Their beneficial effects are mediated through the inhibition of the Ras/PKA pathway, with increased expression of heat shock proteins, along with a consistent increase of both mean and maximal lifespans. These fungal extracts also reduce the toxicity of α-synuclein heterologously expressed in yeast cells, resulting in reduced ROS levels, lower α-synuclein membrane localization, and protein aggregation. The neuroprotective activity of G. frondosa extract was also confirmed in a PD model of Drosophila melanogaster. Taken together, our data suggest the use of G. frondosa and H. erinaceus as functional food to prevent aging and age-related disorders, further supporting the neuro-healthy properties of these medicinal mushroom extracts.     

The strawberry: composition, nutritional quality, and impact on human health

Strawberries are a common and important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to have relevant biological activity in human health. Among these phytochemicals, anthocyanin and ellagitannins are the major antioxidant compounds. Although individual phytochemical constituents of strawberries have been studied for their biological activities, human intervention studies using whole fruits are still lacking. Here, the nutritional contribution and phytochemical composition of the strawberry are reviewed, as is the role played by the maturity, genotype, and storage effects on this fruit. Specific attention is focused on fruit absorption, metabolism, and the possible beneficial biological activity on human health.     

The Role of Bioactive Compounds of Nigella sativa in Rheumatoid Arthritis Therapy—Current Reports

Black cumin (Nigella sativa, NS) is included in the Ranunculaceae family and is classified as a medicinal plant due to very high levels of various bioactive compounds. They determine its therapeutic effects, including anti-inflammatory, anti-allergic, anti-cancer, hypoglycemic, antioxidant, hypotensive, hypolipidemic, and immunomodulating properties. The results of scientific studies indicate a supporting role of black cumin in the treatment of autoimmune diseases, including rheumatoid arthritis, due to the health-promoting properties of its bioactive ingredients. The aim of the current article is to analyze the results of scientific publications on the role of bioactive ingredients contained in black cumin in the treatment of rheumatoid arthritis.