Flavonoids as a therapeutical option for the treatment of thrombotic complications associated with COVID-19.

The SARS-CoV-2 outbreak has been one of the largest public health crises globally, while thrombotic complications have emerged as an important factor contributing to mortality. Therefore, compounds that regulate the processes involved in thrombosis could represent a dietary strategy to prevent thrombotic complications involved in COVID-19. In August 2022, various databases were consulted using the keywords "flavonoids", "antiplatelet", "anticoagulant", "fibrinolytic", and "nitric oxide". Studies conducted between 2019 and 2022 were chosen. Flavonoids, at concentrations mainly between 2 and 300 µM, are capable of regulating platelet aggregation, blood coagulation, fibrinolysis, and nitric oxide production due to their action on multiple receptors and enzymes. Most of the studies have been carried out through in vitro and in silico models, and limited studies have reported the in vivo and clinical effect of flavonoids. Currently, quercetin has been the only flavonoid evaluated clinically in patients with COVID-19 for its effect on D-dimer levels. Therefore, clinical studies in COVID-19 patients analyzing the effect on platelet, coagulant, fibrinolytic, and nitric oxide parameters are required. In addition, further high-quality studies that consider cytotoxic safety and bioavailability are required to firmly propose flavonoids as a treatment for the thrombotic complications implicated in COVID-19.

Chia Oil and Mucilage Nanoemulsion: Potential Strategy to Protect a Functional Ingredient.

Nanoencapsulation can increase the stability of bioactive compounds, ensuring protection against physical, chemical, or biological degradations, and allows to control of the release of these biocompounds. Chia oil is rich in polyunsaturated fatty acids-8% corresponds to omega 3 and 19% to omega 6-resulting in high susceptibility to oxidation. Encapsulation techniques allow the addition of chia oil to food to maintain its functionality. In this sense, one strategy is to use the nanoemulsion technique to protect chia oil from degradation. Therefore, this review aims to present the state-of-the-art use of nanoemulsion as a new encapsulation approach to chia oil. Furthermore, the chia mucilage-another chia seed product-is an excellent material for encapsulation due to its good emulsification properties (capacity and stability), solubility, and water and oil retention capacities. Currently, most studies of chia oil focus on microencapsulation, with few studies involving nanoencapsulation. Chia oil nanoemulsion using chia mucilage presents itself as a strategy for adding chia oil to foods, guaranteeing the functionality and oxidative stability of this oil.

Vasorelaxant Activity of Salvia hispanica L.: Involvement of the Nitric Oxide Pathway in Its Pharmacological Mechanism.

Salvia hispanica L., commonly known as chía, and its seeds have been used since ancient times to prepare different beverages. Due to its nutritional content, it is considered a dietary ingredient and has been reported with many health benefits. Chia seed components are helpful in cardiovascular disease (CVD) by reducing blood pressure, platelet aggregation, cholesterol, and oxidation. Still, its vasodilator effects on the vascular system were not reported yet. The hexanic (HESh), dichloromethanic (DESh), and methanolic (MESh) extracts obtained from chía seeds were evaluated on an aortic ring ex-vivo experimental model. The vasorelaxant efficacy and mechanism of action were determined. Also, phytochemical data was obtained through 13C NMR-based dereplication. The MESh extract showed the highest efficacy (Emax = 87%), and its effect was partially endothelium-dependent. The mechanism of action was determined experimentally, and the vasorelaxant curves were modified in the presence of L-NAME, ODQ, and potassium channel blockers. MESh caused a relaxing effect on KCl 80 mM-induced contraction and was less potent than nifedipine. The CaCl2-induced contraction was significantly decreased compared with the control curve. Phytochemical analysis of MESh suggests the presence of mannitol, previously reported as a vasodilator on aortic rings. Our findings suggest NO-cGMP pathway participation as a vasodilator mechanism of action of S. hispanica seeds; this effect can be attributed, in part, to the mannitol presence. S. hispanica could be used in future research focused on antihypertensive therapies.

Proteins and peptides from vegetable food sources as therapeutic adjuvants for the type 2 diabetes mellitus.

Proteins and peptides are fundamental components of the cereals, pseudocereals, and legumes, giving them numerous health-beneficial properties. Previous studies have demonstrated that these molecules exerted effects on current therapeutic targets related to type 2 diabetes mellitus, such as incretin hormones (responsible for appetite suppression), dipeptidyl peptidase IV (an enzyme involved in the inactivation and degradation of the incretin hormones), and glucose transporters (molecules that transport glucose in or out of cells). Therefore, this review presents the current biological activity of protein derivatives and peptides isolated from cereals, pseudocereals, and legumes on these therapeutic markers, highlighting their potential as a possible pharmacological treatment for type 2 diabetes mellitus.

Amaranth, quinoa and chia bioactive peptides: a comprehensive review on three ancient grains and their potential role in management and prevention of Type 2 diabetes.

Worldwide prevalence of Type 2 Diabetes (T2D) has become a major concern with several implications for public health, economy, and social well-being, especially in developing countries. Conventional pharmacological management of T2D have proved effective, but possess underlying side effects, leading the scientific community to research alternative compounds that exert beneficial effects on current therapeutic targets of T2D. Bioactive peptides (BAPs) from food sources, have shown relative advantages in this matter, moreover, BAPs have proved to impart anti-diabetic activity through one or more mechanisms such as enzymatic inhibition of α-glucosidase, α-amylase and DPP-IV. Several plants and animal have been used as protein sources of anti-diabetic BAPs, in the sense of this matter, the pseudo-cereals amaranth and quinoa, along with the ancestral grain chia, have gained attention. Due, to their high protein content and balanced amino-acid composition, along with proved anti-diabetic features, the three seeds are top choices for the obtention of anti-diabetic BAPs. With a comprehensive overview of the most recent reported in silico and in vitro anti-diabetic studies in relation to biomarkers α-glucosidase, α-amylase and DPP-IV, the present review aims to examine the current knowledge of amaranth, quinoa and chia derived anti-diabetic BAPs and their effects on T2D therapeutic markers.

A Pharmacokinetic Study of Mix-160 by LC-MS/MS: Oral Bioavailability of a Dosage Form of Citroflavonoids Mixture.

This study was performed to evaluate and compare the pharmacokinetic parameters between two dosage formulations of hesperidin and naringenin: mixture and tablet. Our objective was to determine that the flavonoid tablet does not significantly modify the pharmacokinetic parameters compared with the mixture. For this study, we administered 161 mg/kg of either mixture (Mix-160) or tablet composed of hesperidin and by intragastric administration. Blood microsamples were collected from tail vein up to 24 h. Serum flavonoid extraction was performed by solid phase extraction and analyzed by LC-MS/MS of triple quadrupole (QqQ). Serum concentration vs. time plot showed that data fitted for a first-order model. The pharmacokinetic parameters were calculated by a noncompartmental model. The results showed that the absorption constant is higher than the elimination constant. The first concentration was found at five minutes, and minimal concentration at 24 h after administration, suggesting a enterohepatic recirculation phenomena and regulation of liver cytochromes' activity. We did not find meaningful differences between the pharmacokinetic parameters of both samples. We concluded that tablet form did not interfere with the bioavailability of hesperidin and naringenin, and it could be a suitable candidate for developing a drug product.

Antibacterial peptide fractions from chia seeds (Salvia hispanica L.) and their stability to food processing conditions.

Foodborne pathogens are one of the major causes of food deterioration and a public health concern worldwide. Antimicrobial peptides (AMPs) encrypted in protein sequences from plants, such as chia (Salvia hispanica), might have a crucial role in the inhibition of bacteria. In this study, the antibacterial activity and stability of chia peptide fractions (CPFs) were evaluated for potential applications in food preservation. Three CPFs (F < 1, F 1-3, and F 3-5 kDa) were obtained by enzymatic hydrolysis of a protein-rich fraction and subsequent ultrafiltration. Gram-positive bacteria were susceptible to F < 1. This fraction's more significant inhibition effect was reported against Listeria monocytogenes (635.4 ± 3.6 µg/mL). F < 1 remained active after incubation at 4-80 °C and a pH range of 5-8 but was inactive after exposure to pepsin and trypsin. In this sense, F < 1 could be suitable for meat and dairy products at a maximum reference level of 12-25 mg/kg. Multicriteria analysis suggested that KLKKNL could be the peptide displaying the antimicrobial activity in F < 1. These results demonstrate the potential of this sequence as a preservative for controlling the proliferation of Gram-positive bacteria in food products.

Bioactive Peptides as Therapeutic Adjuvants for Cancer.

Conventional cancer treatments such as chemotherapy, radiotherapy and surgery cause serious side effects on cancer patients which decrease their quality of life. In the past few years, cancer patients have been interested in the use of complementary medicine to improve the efficacy of conventional cancer treatments and decrease the side effects. Among the broad spectrum of complementary medicine, bioactive peptides from natural sources have gained great interest due to their potential use in the treatment of chronical diseases such as cancer. This review reports an updated survey of bioactive peptides, from natural sources, with anticancer and immunomodulatory activities obtained by enzymatic hydrolysis. Several peptides have demonstrated anticancer effects on In Vitro and In Vivo essays, such as: selective cytotoxicity, inhibition of growth, tumor size reduction and immunomodulation. However, there is absence of formal pharmacokinetic profiles and standardized extraction procedures of bioactive peptides. Further clinical trials are necessary to verify these anticancer effects and, facilitate the use of peptides in the treatment of cancer.

Renal and Hepatic Disease: Cnidoscolus aconitifolius as Diet Therapy Proposal for Prevention and Treatment.

The lack of prevention of noncommunicable diseases (NCDs) has caused an increase in the mortality rate including conditions such as chronic kidney disease (CKD) and liver disease (LD). The high complexity of CKD and LD results in alterations in the metabolism of carbohydrates, proteins, and lipids. One of the changes observed in CKD and LD is the decrease in albumin, elevation of PO4-3, K+, creatinine, urea, and transaminase enzymes. The pharmacological treatment is expensive. Nowadays, phytotherapy is an option to treat NCDs. Aqueous, ethanolic, methanolic, and ethyl acetate extracts of Cnidoscolus aconitifolius have shown nephroprotective and hepatoprotective potential and can be an alternative to prevent and treat CKD and LD. C. aconitifolius, known as Chaya by Mayas in Yucatán, is a shrub that is consumed in Mexico and in the world, has a low cost, it is very accessible, and can growth in extreme weather. The aim of this review is to show the potential biological effects of C. aconitifolius extracts, and the association of the phytochemicals in the extract. It is known that different solvents result in the uptake of different phytochemicals. These have shown various effects such as hypoglycemic, hypotensive, hypolipidemic, and antioxidant, being a natural alternative to the treatment of NCDs.Key teaching pointsPhytotherapy is a proposal to treat NCDs.Cnidoscolus aconitifolius extracts have a hypotensive effect.Cnidoscolus aconitifolius extracts reduce blood sugar in diabetic rats.Chaya extracts are no toxic for renal and hepatic cells.

Antihyperglycemic and hypoglycemic activity of Mayan plant foods in rodent models.

BACKGROUND: Postprandial hyperglycemia and decreased insulin secretion are relevant to risk factors in the development of type 2 diabetes and its complications. Plant foods with antidiabetic properties could be an affordable alternative in the prevention and treatment of this disease. In the present study, the antihyperglycemic and hypoglycemic activity of Bixa orellana, Psidium guajava L., Cucurbita moschata, Raphanus sativus L. and Brassica oleracea var. capitata - Mayan plant foods - were evaluated at doses of 5 and 10 mg kg-1 . Antihyperglycemic activity was measured in healthy Wistar rats and those with obesity induced by high-sucrose diet (group HSD) (20%). The hypoglycemic activity was measure in healthy CD1 mice. RESULTS: Fasting glucose, Lee index and the body weight of HSD rats increased significantly (P ≤ 0.05) after 12 weeks of induction compared to healthy rats. In healthy rats, P. guajava and Bixa orellana (10 mg kg-1 ) demonstrated higher and statistically different (P ≤ 0.05) antihyperglycemic activity compared to control acarbose (0.5 mg kg-1 ). In the HSD rat group, all Mayan plant foods (10 mg kg-1 ) demonstrated antihyperglycemic activity statistically equal (P ≤ 0.05) to control acarbose. However, Brassica oleracea and R. sativus registered the highest antihyperglycemic activity. Bixa orellana and P. guajava (5 mg kg-1 ) showed similar hypoglycemic activity (P ≤ 0.05) to glibenclamide (0.5 mg kg-1 ) but was not significant (P ≤ 0.05) compared to insulin (5 UI kg-1 ). CONCLUSION: The present study provides valuable evidence on the possible health benefits of Mayan plant foods. These foods could contribute to the development of therapeutic diet strategies for the prevention and treatment of diabetes. © 2021 Society of Chemical Industry.

Biological activity of Stevia rebaudiana Bertoni and their relationship to health.

The leaves of Stevia rebaudiana Bertoni has nutrients and phytochemicals, which make it an adequate source for the extraction and production of functional food ingredients. Preclinical and clinical studies suggest therapeutic and pharmacological applications for stevia and their extracts because they are not toxic and exhibit several biological activities. This review presents the biological activity of Stevia rebaudiana Bertoni and their relationship to antidiabetic, anticariogenic, antioxidant, hypotensive, antihypertensive, antimicrobial, anti-inflammatory and antitumor activities. Consumption and adverse effects were also reviewed.

Encapsulation of vegetable oils as source of omega-3 fatty acids for enriched functional foods.

Polyunsaturated omega-3 fatty acids (PUFAs), a functional component present in vegetable oils, are generally recognized as being beneficial to health. Omega-3 PUFAs are rich in double bonds and unsaturated in nature; this attribute makes them highly susceptible to lipid oxidation and unfit for incorporation into long shelf life foods. The microencapsulation of oils in a polymeric matrix (mainly polysaccharides) offers the possibility of controlled release of the lipophilic functional ingredient and can be useful for the supplementation of foods with PUFAs. The present paper provides a literature review of different vegetable sources of omega-3 fatty acids, the functional effects of omega-3 fatty acids, different microencapsulation methods that can possibly be used for the encapsulation of oils, the properties of vegetable oil microcapsules, the effect of encapsulation on oxidation stability and fatty acid composition of vegetable oils, and the incorporation of long-chain omega-3 polyunsaturated fatty acids in foods.

Novel peptides derived from S. hispanica seeds induce selective cytotoxicity on human cancer cells.

Cancer prevails as one of the major health concerns worldwide due to the consistent rise in incidence and lack of effective therapies. Previous studies identified the peptides KLKKNL, MLKSKR, and KKYRVF from Salvia hispanica seeds and stated their selective anticancer activity. Thus, this study aimed to determine the cell death pathway induced by these peptides on five cancer cell lines (MCF-7, Caco2, HepG2, DU145, and HeLa). Based on the results of this work, it is possible to suggest that KLKKNL primarily induces selective cancer cell death through the apoptotic pathway in the Caco2 and HeLa lines. On the other hand, the peptide KKYRVF reported the highest statistical (p < 0.05) selective cytotoxic effect on the MCF-7, Caco2, HepG2, and DU145 cancer cell lines by induction of the necrotic pathway. These findings offer some understanding of the selective anticancer effect of KLKKNL, MLKSKR, and KKYRVF.

Therapeutic Effects of Amaranth: Analysis of the Antidiabetic Potential of the Plant.

Amaranth is a pseudocereal rich in macronutrients and micronutrients, with about 60 species cultivated worldwide. It is a high nutritional value food because of its many essential amino acids. Recent investigations demonstrate that the phytochemicals and extracts of amaranth have beneficial effects on health, including antidiabetic potential, a decrease in plasmatic cholesterol and blood pressure, and protection from oxidative stress and inflammation. Nowadays, type 2 diabetes has increased worldwide, becoming a problem of public health that makes it necessary to look for alternative strategies for its prevention and treatment. This review aims to summarize the antidiabetic potential of diverse species of the Amaranth genus. A bibliographical review was updated on the plant's therapeutic potential, including stem, leaves, and seeds, to know the benefits and potential as an adjuvant in treating and managing diabetes and associated pathologies (hypertension, dyslipidemia, and heart disease). This analysis contributes to the generation of knowledge about the therapeutic effects of amaranth, promoting the creation of new products, and the opportunity to conduct clinical trials to assess their safety and efficacy.

In vitro evaluation of multifunctional peptides PW, PF, PPG, PM, IW, and SW for metabolic syndrome management.

Multifunctional peptides derived from various food sources, including ancestral grains, hold significant promise for managing metabolic syndrome. These bioactive peptides exhibit diverse properties that collectively contribute to improving the components of metabolic syndrome. In this study, we investigated the in vitro multifunctionality of six peptides (PW, PM, SW, PPG, PW, and IW) identified through in silico analysis and chemically synthesized. These peptides were evaluated for their potential to address metabolic syndrome-related activities such as antidiabetic, antiobesity, antihypertensive, and antioxidative properties. Assessment included their capacity to inhibit key enzymes associated with these activities, as well as their free radical scavenging and cellular antioxidative activities. Principal component analysis was employed to cluster the peptides according to their multifunctionality. Our results revealed that peptides containing tryptophan (SW, PW, and IW) exhibited the most promising multifunctional attributes, with SW showing particularly high potential. This multifunctional peptide represents a promising avenue for addressing metabolic syndrome.

Therapeutic Potential of Brassica oleracea and Raphanus sativus Aqueous Extracts on a Prediabetic Rat Model.

Type 2 diabetes (T2D) is a serious health problem, and its prevalence is expected to increase worldwide in the years ahead. Cruciferous vegetables such as Brassica oleracea var. capitata L. (green cabbage) and Raphanus sativus L. (radish) have therapeutic properties that can be used to support the treatment of T2D. This study evaluated the effect of B. oleracea (BAE) and R. sativus (RAE) aqueous extracts on zoometric parameters, glycemic profiles, and pancreas and liver in prediabetic rats induced by a high-sucrose diet (HSD). BAE and RAE were administered to male HSD-induced Wistar rats (n = 35) at 5 and 10 mg/kg doses for 5 weeks. Zoometric and biochemical changes were measured, and then the pancreas and liver histological preparations were analyzed to observe the protective effect. BAE decreased feed intake and weight gain. Both extracts decreased fasting glucose and insulin levels compared with control (not treated), although not significantly (P > .05). The extracts significantly (P < .05) reduced homeostatic model assessment for insulin resistance, homeostasis model assessment of ß-cell function, and glucose intolerance, similar to metformin control. In addition, minor damage occurred in the pancreas and liver. The results indicated that BAE and RAE decreased weight gain, improved glucose regulation, and protected the pancreas and liver in HSD rats. Therefore, they have multiple therapeutical properties and may be helpful in the prevention of T2D.

Bioassay-guided identification of antithrombotic compounds from Cnidoscolus aconitifolius (Mill.) I. M. Jhonst.: molecular docking, bioavailability, and toxicity prediction.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Conventional antithrombotic therapy has reported hemorrhagic accidents. Ethnobotanical and scientific reports point to Cnidoscolus aconitifolius as an antithrombotic adjuvant. Previously, C. aconitifolius leaves ethanolic extract displayed antiplatelet, anticoagulant, and fibrinolytic activities. This work aimed to identify compounds from C. aconitifolius with in vitro antithrombotic activity through a bioassay-guided study. Antiplatelet, anticoagulant, and fibrinolytic tests guided the fractionation. Ethanolic extract was subjected to a liquid-liquid partitioning, followed by vacuum liquid, and size exclusion chromatography to obtain the bioactive JP10B fraction. The compounds were identified through UHPLC-QTOF-MS, and their molecular docking, bioavailability, and toxicological parameters were determined computationally. Kaempferol-3-O-glucorhamnoside and 15(S)-HPETE were identified; both showed affinity for antithrombotic targets, low absorption, and safety for human consumption. Further in vitro and in vivo evaluations will better understand their antithrombotic mechanism. This bioassay-guided fractionation demonstrated that C. aconitifolius ethanolic extract has antithrombotic compounds.Communicated by Ramaswamy H. Sarma.

Bioactive compounds and functional foods as coadjuvant therapy for thrombosis.

Cardiovascular diseases (CVDs) are the leading cause of death. The most common cardiovascular pathologies are thromboembolic diseases. Antithrombotic therapy prevents thrombus formation or dissolves that previously constituted. However, it presents a high rate of accidents such as gastric bleeding and cerebrovascular embolism. Plant foods and their secondary metabolites have been reported to regulate blood hemostasis. This review article aims to propose plant foods and their metabolites as adjuvant therapy for the management of thromboembolic diseases. Various databases were consulted, using antiplatelet, anticoagulant, and fibrinolytic as key terms. In total, 35 foods and 24 secondary metabolites, via in vitro, in vivo, and clinical studies, have been reported to regulate platelet aggregation, blood coagulation, and fibrinolysis. According to the studies presented in this review, plant foods with effects at concentrations less than 50 µg mL-1 and secondary metabolites with IC50 less than 100 µM can be considered agents with high antithrombotic potential. This review suggests that plant foods and their secondary metabolites should be used to develop foods, ingredients and nutraceuticals with functional properties. The evidence presented in this review shows that plant foods and their bioactive compounds could be used as adjuvants for the treatment and prevention of thrombotic complications. However, further in vivo and clinical trials are required to establish effective and safe doses.

Antibacterial properties of peptides from chia (Salvia hispanica L.) applied to pork meat preservation.

Chia-derived peptides might represent a novel alternative to conventional preservatives in food. Despite the antibacterial potential of these molecules, their food application is still limited. This study aimed to evaluate chia-derived peptides' antibacterial and antibiofilm potential in food preservation. The peptides YACLKVK, KLKKNL, KLLKKYL, and KKLLKI were synthesized, and their antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Salmonella Enteritidis was evaluated through microdilution tests. A bacterial killing kinetic assay determined bacterial growth over time. The ability to prevent and eradicate S. aureus biofilm was assessed by crystal violet staining. The hemolytic and cytotoxic activities were determined in human red blood cells and fibroblasts using free hemoglobin detection and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays, respectively. Finally, a microbial challenge was performed on meat samples inoculated with L. monocytogenes and S. Enteritidis to determine their inhibitory effects on pork meat. Results showed the potential antibacterial activity of these peptides, with minimum inhibitory concentrations ranging from 0.23 to 5.58 mg/mL. Biofilm inhibition percentages were above 40%, and eradication percentages were lower than 20%. In vitro assays in human red blood cells and fibroblasts demonstrated that peptides are not hemolytic or cytotoxic agents. In microbiological challenge testing, KKLLKI showed the most promising antibacterial effects against S. Enteritidis on refrigerated pork meat samples. These findings suggest that chia-derived peptides have the potential as natural food preservatives due to their antibacterial and antibiofilm properties. Notably, KKLLKI demonstrated promising antibacterial effects against Salmonella spp. on a complex food matrix, such as pork meat. PRACTICAL APPLICATION: Chia-derived peptides can be a safer alternative to synthetic preservatives in the food industry because the latter may be detrimental to human health. Salmonella spp. growth on chilled pork meat was shown to be inhibited by the peptide KKLLKI, indicating that the use of these peptides may offer a more secure and natural alternative to synthetic preservatives.

Using plant-based compounds as preservatives for meat products: A review.

The susceptibility of meat and meat products (MP) to oxidation and microbial deterioration poses a risk to the nutritional quality, safety, and shelf life of the product. This analysis provides a brief overview of how bioactive compounds (BC) impact meat and MP preservation, and how they can be utilized for preservation purposes. The use of BC, particularly plant-based antioxidants, can reduce the rate of auto-oxidation and microbial growth, thereby extending the shelf life of MP. These BC include polyphenols, flavonoids, tannins, terpenes, alkaloids, saponins, and coumarins, which have antioxidant and antimicrobial properties. Bioactive compounds can act as preservatives and improve the sensory and physicochemical properties of MP when added under appropriate conditions and concentrations. However, the inappropriate extraction, concentration, or addition of BC can also lead to undesired effects. Nonetheless, BC have not been associated with chronic-degenerative diseases and are considered safe for human consumption. MP auto-oxidation leads to the generation of reactive oxygen species, biogenic amines, malonaldehyde (MDA), and metmyoglobin oxidation products, which are detrimental to human health. The addition of BC at a concentration ranging from 0.025 to 2.5% (w/w in powdered or v/w in oil or liquid extracts) can act as a preservative, improving color, texture, and shelf life. The combination of BC with other techniques, such as encapsulation and the use of intelligent films, can further extend the shelf life of MP. In the future, it will be necessary to examine the phytochemical profile of plants that have been used in traditional medicine and cooking for generations to determine their feasibility in MP preservation.