The seed of industrial hemp (Cannabis sativa L.): Nutritional Quality and Potential Functionality for Human Health and Nutrition.

Hempseeds, the edible fruits of the Cannabis sativa L. plant, were initially considered a by-product of the hemp technical fibre industry. Nowadays, following the restorationing of the cultivation of C. sativa L. plants containing an amount of delta-9-tetrahydrocannabinol (THC) <0.3% or 0.2% (industrial hemp) there is a growing interest for the hempseeds production due to their high nutritional value and functional features. The goal of this review is to examine the scientific literature concerning the nutritional and functional properties of hempseeds. Furthermore, we revised the scientific literature regarding the potential use of hempseeds and their derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic-degenerative diseases on animal models and humans too. In the first part of the work, we provide information regarding the genetic, biochemical, and legislative aspects of this plant that are, in our opinion essential to understand the difference between "industrial" and "drug-type" hemp. In the final part of the review, the employment of hempseeds by the food industry as livestock feed supplement and as ingredient to enrich or fortify daily foods has also revised. Overall, this review intends to encourage further and comprehensive investigations about the adoption of hempseeds in the functional foods field.

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut⁻Retina Axis.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30⁻50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

A simple microsatellite-based method for hazelnut oil DNA analysis.

Molecular food traceability requires continuous updates to identify more robust, efficient and affordable methodologies to guarantee food quality and safety and especially consumers' health. Available commercial kits are often unsatisfactory and require modifications to successfully detect single components on complex and transformed food matrices. Here we report a simple method for molecular traceability of cold-pressed hazelnut oil based on microsatellite DNA markers. Different genomic extraction methodologies were tested and a total genome pre-amplification step was applied on PCR-negative samples. PCR-capillary electrophoresis using nine microsatellites demonstrates the accuracy of the fingerprint analysis even for filtered oil.

Impact of Omega-3 Fatty Acids on the Gut Microbiota.

Long-term dietary habits play a crucial role in creating a host-specific gut microbiota community in humans. Despite the many publications about the effects of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined. The few studies completed in adults showed some common changes in the gut microbiota after omega-3 PUFA supplementation. In particular, a decrease in Faecalibacterium, often associated with an increase in the Bacteroidetes and butyrate-producing bacteria belonging to the Lachnospiraceae family, has been observed. Coincidentally, a dysbiosis of these taxa is found in patients with inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by reverting the microbiota composition in these diseases, and increase the production of anti-inflammatory compounds, like short-chain fatty acids. In addition, accumulating evidence in animal model studies indicates that the interplay between gut microbiota, omega-3 fatty acids, and immunity helps to maintain the intestinal wall integrity and interacts with host immune cells. Finally, human and animal studies have highlighted the ability of omega-3 PUFAs to influence the gut-brain axis, acting through gut microbiota composition. From these findings, the importance of the omega-3 connection to the microbiota emerges, encouraging further studies.

Effect of Dietary ω-3 Polyunsaturated Fatty Acid DHA on Glycolytic Enzymes and Warburg Phenotypes in Cancer.

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.

Pasta containing tartary buckwheat sprouts prevents DNA damage in spontaneously hypertensive rats.

Recent studies have shown that DNA damage occurs more often in hypertensive patients than non-hypertensive individuals. Here, we analyzed the in vivo effect of pasta containing 30% of tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY) to elucidate if TBSP could have an anti-genotoxic effect in hypertensive animal models. Both SHRs and WKY rats were divided into two groups and fed for six weeks with 5 g of TBSP and durum wheat flour commercial pasta, respectively. Our results showed that a diet rich in TBSP has anti-genotoxic effect. Indeed, SHRs fed with TBSP exhibited a significant decrease in DNA damage (38%) and more efficient DNA repair (84%) compared to SHRs fed with commercial pasta.

Development of gluten-free bread using tartary buckwheat and chia flour rich in flavonoids and omega-3 fatty acids as ingredients.

In this study, chia seed flour, which is rich in omega-3 alpha-linolenic acid, and common and tartary buckwheat flour, which has a high antioxidant activity, were integrated into different types of bread with the aim of improving their nutritional value and healthy features. Our results indicate that bread made with chia and tartary buckwheat flour was more acceptable in many nutritional aspects compared to the control (common wheat bread); it contained a higher amount of protein (20%), insoluble dietary fibres (74%), ash (51%), and alpha-linolenic acid (67.4%). Moreover, this bread possessed lower energy (14%) and carbohydrate contents (24%) compared to the control. Tartary buckwheat also improved the total antioxidant capacity of the bread (about 75%) and provided a considerable amount of flavonoids, which are healthy non-nutritional compounds. Overall, chia and tartary buckwheat represent excellent raw materials for the formulation of gluten-free bread with high nutritional value.

A new "functional" pasta containing tartary buckwheat sprouts as an ingredient improves the oxidative status and normalizes some blood pressure parameters in spontaneously hypertensive rats.

Epidemiological studies have reported that some foods, particularly those rich in (poly)phenols, may reduce cardiovascular risk and metabolic disorders such as hypertension. Buckwheat sprouts have been suggested as a new raw material for the production of functional foods due to their high content of healthy compounds such as rutin and quercetin. The aim of this paper is to evaluate the biological hypotensive and antioxidant responses of pasta containing tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHR). In this study, dry tartary buckwheat sprouts were milled to obtain a powder that was used in the production of pasta containing 30% dry buckwheat sprouts and 70% durum wheat semolina. Afterwards, we analyzed the in vitro TBSP features compared with the control (durum wheat flour pasta, DWFP), and the in vivo effects of TBSP on SHR and their normotensive counterpart, Wistar Kyoto rats (WKY rats). The total phenolic content and antioxidant activity were higher in TBSP compared to DWFP. The results showed that SHR fed TBSP exhibited higher plasma levels of the endogenous vasodilators bradykinin (BK) and nitric oxide (NO), a lower level of the vasoconstrictor endothelin-1 (ET-1), and an improved antioxidant capacity. These data suggest that TBSP may help reduce hypertension and oxidative stress in vivo.

Dietary ω -3 polyunsaturated fatty acid DHA: a potential adjuvant in the treatment of cancer.

ω -3 Polyunsaturated fatty acids (PUFAs), mainly present in fish oil, are part of the human diet. Among PUFAs, docosahexaenoic acid (DHA) has received particular attention for its anti-inflammatory, antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties. These data suggest that DHA can exert antitumor activity potentially representing an effective adjuvant in cancer chemotherapy. This review is focused on current knowledge supporting the potential use of DHA for the enhancement of the efficacy of anticancer treatments in relation to its ability to enhance the uptake of anticancer drugs, regulate the oxidative status of tumor cells, and inhibit tumor cell invasion and metastasis.

Docosahexaenoic acid inhibits invasion of human RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-modulation of granzyme B expression.

Fish oil-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) inhibit invasion of some tumor cell types in vitro and in vivo. The mechanisms underlying this activity are unclear. Here, we examined the capability of n-3 PUFA-docosahexaenoic acid (22:6n-3; DHA) to affect the invasiveness of human RT112 urinary bladder and PT45 pancreatic carcinoma cell lines in vitro and the mechanism underlying this activity; n-6 PUFA-arachidonic acid (20:4n-6; AA) served as control. We showed that, in contrast to AA, 25, 50 and 100 µM DHA significantly inhibited in a dose-dependent manner the invasion through Matrigel of both RT112 and PT45 cells. Then, we analyzed whether the serine proteinase granzyme B (GrB), originally known as cytotoxic molecule of lymphocytes and recently also characterized for its extracellular functions such as invasion promotion of bladder cancer cells, might be involved in the invasion inhibitory activity exerted by DHA. We demonstrated that, accordingly to RT112 bladder cancer cells, PT45 cells expressed GrB and GrB promoted their invasion, since stealth RNA interference-mediated down-regulation of GrB dramatically suppressed PT45 cell invasion. Notably, we also showed that, in contrast to AA, 25, 50 and 100 µM DHA induced a dose-dependent down-modulation of GrB expression in both RT112 and PT45 cells. In conclusion, DHA can reduce the invasive phenotype of bladder and pancreatic carcinoma cells, and we provide the first evidence for a possible causative role of GrB in DHA-induced inhibition of cancer cell invasion. The potential use of fish oil as adjuvant antibladder and antipancreatic cancer agent may be suggested.

Docosohaexanoic acid-supplemented PACA44 cell lines and over-activation of Krebs cycle: an integrated proteomic, metabolomic and interactomic overview.

Recent investigations have pointed out the ability of fatty acids, in particular of docosohaexanoic acid (DHA), to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line through a series of mechanisms which has been hypothesized to mimic apoptosis. While preliminary evidences indicated the involvement of lipid-targeting oxidative stress in DHA-induced apoptotic processes, mainly through the alteration of the glutathione (GSH) homeostasis and oxidized-glutathione (GSSG) turn-over through their extra-cellular extrusion, no further molecular data have been hitherto accumulated. To this end, we hereby propose simultaneous protein-targeting and metabolite-oriented analyses, which have been integrated through the auxilium of in silico elaboration of those protein-protein interaction pathways and enrichment of biological/molecular functions. To determine the most suitable time window for the early onset of the DHA-triggered apoptosis phenomena we performed flow cytometry-based apoptotic assessment at 24, 48 and 72 h. Results indicated that the focus of apoptosis onset ranged from 48 to 72 h. From these analyses it emerges that the metabolism of control human PaCa-44 pancreatic cancer cell line mainly leans on glycolytic pathways, while it is promptly switched to Kreb's cycle activation (overexpression of Kreb's cycle enzymes in DHA-treated cells against controls) and modulation of the GSH homeostasis through an increased production of GSSG-reducing NADPH coenzyme via the shift of the glycolytic energy flux towards the pentose phosphate pathway. Interestingly, it also emerges a role for structural protein alteration in DHA-treated cells, which might be linked to cytoskeletal alterations occurring during apoptosis.

Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer.

It has recently become clear the role played by alterations in apoptosis during the development of several chronic diseases (i.e. inflammatory, neurodegenerative and neoplastic pathologies). For this reason, the research for possible therapeutic strategies involving the modulation of the apoptotic pathways has attracted considerable interest in the past few years. In particular, it has been shown that apoptosis may be induced or inhibited by a variety of nutritional compounds providing health benefits. The aim of this review is to examine the ability of different dietary polyunsaturated fatty acids (PUFAs) to induce apoptosis, especially in the cancer field. The molecular effects of different PUFAs found in dairy products, meat, fish, vegetable seeds and oils, and known to affect the incidence and progression of cancer and other chronic diseases, will be analyzed. To this aim, our effort will concentrate in critically reviewing the published works concerning the effects of: (a) the n-6 PUFAs gamma-linolenic acid, arachidonic acid, and conjugated linoleic acid; (b) the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid on the apoptotic process. We will also pay attention to the recent findings regarding the possible role of PUFAs as regulators of the endoplasmic reticulum stress-pathway of apoptosis.

Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation.

We investigated the ability of fatty acids to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line and the mechanism(s) underlying apoptosis. Butyric acid, alpha-linoleic acid, and docosahexaenoic acid (DHA) were supplemented at 200 microM concentration in the medium of cell cultures. Our results showed that all fatty acids inhibited cell growth, whereas only DHA induced cell apoptosis. An oxidative process was implicated in apoptosis induced by DHA because butylated hydroxytoluene and vitamin E prevented lipid peroxidation and reversed apoptosis. Intracellular and extracellular glutathione [reduced glutathione (GSH) and oxidized glutathione (GSSG)] concentrations were measured following DHA treatment in the presence or in the absence of GSH extrusion inhibitors such as cystathionine or methionine. DHA induced intracellular GSH depletion without affecting intracellular GSSG concentration and increased extracellular GSH and GSSG levels. Intracellular GSH depletion and extracellular GSH increase were both reversed by cystathionine. Inhibition of active GSH extrusion from the cell by cystathionine or methionine completely reversed lipid peroxidation and apoptosis. These data document the antiproliferative and apoptotic activities of DHA. The date provide evidence that intracellular GSH depletion represents an active extrusion process rather than a consequence of an oxidative stress, suggesting a causative role of GSH depletion in DHA-induced apoptosis.