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.

Neuroprotective Effect Of Peptide Fractions from Chia (Salvia hispanica) on H2O2-Induced Oxidative Stress-Mediated Neuronal Damage on N1E-115 Cell Line.

Neurodegenerative diseases (ND) affect around a billion people worldwide. Oxidative stress plays a critical role in the activation of neuronal death mechanisms, implicated in the ND etiology. In the present research, the neuroprotective effect of the S. hispanica protein derivatives is evaluated, on neuronal cells N1E-115, after the damage induction with H2O2. From the protein-rich fraction of S. hispanica, three peptide fractions were obtained (3-5, 1-3 y < 1 kDa) and its neuroprotective effect on neuronal cells N1E-115 was evaluated, through the antioxidant pathway. In the toxicity assay, the peptide fractions showed viability greater than 90%. When N1E-115 cells were incubated with 100 µM H2O2, fractions 1-3 and < 1 kDa, presented cell viability of 66.64% ± 3.2 and 67.32% ± 2.8, respectively. Fractions 1-3 and < 1 kDa reduced by 41.73% ± 3.2 and 40.87% ± 2.8, respectively, the ROS production compared to the control, without significant statistical difference between both fractions (p < 0.05), while F3-5 kDa, only reduced the ROS production by 21.95% ± 2.4. The protective effect observed in the < 3 kDa fractions could be associated with its antioxidant activity, which represents an important study target.

Peptides from Mucuna pruriens L., with protection and antioxidant in vitro effect on HeLa cell line.

BACKGROUND: Mucuna pruriens L. is a legume sown in the Mexican southeast with an important protein content. Studies have shown the potential use of by-products derived from Mucuna as a functional food because of the hypoglycemic and antihypertensive activities. Thus, this study aims to assess the antioxidant and protective effect of the peptide fractions derived from M. pruriens L., in vitro on the HeLa cell line. An enzymatic hydrolysis with pepsin-pancreatin was performed on the total protein concentrate, from which five peptide fractions were obtained. RESULTS: All protein derivatives from M. pruriens L., except F5-10 kDa, decreased the hydrogen peroxide production by more than 50%. The highest antioxidant activity was exhibited by F1-3 kDa, which lowered the intracellular reactive oxygen species by 207 ± 4.20%. No significant differences were found in the protective effects of the protein hydrolysate, F5-10 kDa, F3-5 kDa and F1-3 kDa relative to the N-acetylcysteine control group. CONCLUSION: This elucidated the potential action mechanisms of M. pruriens L. protein derivatives for future investigations and their role in the prevention and treatment of oxidative stress. © 2019 Society of Chemical Industry.

Protein hydrolysates and ultrafiltered < 1 KDa fractions from Phaseolus lunatus, Phaseolus vulgaris and Mucuna pruriens exhibit antihyperglycemic activity, intestinal glucose absorption and α-glucosidase inhibition with no acute toxicity in rodents.

BACKGROUND: Protein hydrolysates from food plants, such as legumes, have emerged as a new alternative to treat hyperglycemia, an important risk factor contributing to the development of type 2 diabetes mellitus (T2DM) and its complications. The aim of this work was to assess the antihyperglycemic activity and inhibition of α-glucosidase, and intestinal glucose absorption, and acute toxicity of total hydrolysates and < 1 kDa fractions from Phaseolus lunatus L., Phaseolus vulgaris L., and Mucuna pruriens (L.) DC., obtained by hydrolysis with Alcalase®-Flavourzyme® or pepsine-pancreatin enzymatic systems. RESULTS: In vivo results showed that three of six total hydrolysates and four of six < 1 kDa fractions suppressed starch-induced postprandial hyperglycemia (ED50 range between 1.4 and 93 mg kg-1 ). In vitro, total hydrolysates and fractions, particularly from M. pruriens, inhibited carbohydrate intestinal absorption (from 19.2 to 40%), and α-glucosidase activity (IC50 from 0.86 to 75 mg mL-1 ). Finally, none of the hydrolysates and fractions tested did not show any signs of toxicity (LD50 > 5000 mg kg-1 ). CONCLUSION: These results suggest that hydrolysates and < 1 kDa fractions from P. lunatus, P. vulgaris and M. pruriens are suitable candidates to treat or prevent T2DM. © 2018 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.

Some Nutritional Characteristics of Enzymatically Resistant Maltodextrin from Cassava (Manihot esculenta Crantz) Starch.

Cassava (Manihot esculenta Crantz) native starch was treated with pyroconversion and enzymatic hydrolysis to produce a pyrodextrin and an enzyme-resistant maltodextrin. Some nutritional characteristics were quantified for both compounds. Pyroconversion was done using a 160:1 (p/v) starch:HCl ratio, 90 °C temperature and 3 h reaction time. The resulting pyrodextrin contained 46.21% indigestible starch and 78.86% dietary fiber. Thermostable α-amylase (0.01%) was used to hydrolyze the pyrodextrin at 95 °C for 5 min. The resulting resistant maltodextrin contained 24.45% dextrose equivalents, 56.06% indigestible starch and 86.62% dietary fiber. Compared to the cassava native starch, the pyrodextrin exhibited 56% solubility at room temperature and the resistant maltodextrin 100%. The glycemic index value for the resistant maltodextrin was 59% in healthy persons. Its high indigestible starch and dietary fiber contents, as well as its complete solubility, make the resistant maltodextrin a promising ingredient for raising dietary fiber content in a wide range of foods, especially in drinks, dairy products, creams and soups.

Nutritional, amylolytic enzymes inhibition and antioxidant properties of bread incorporated with Stevia rebaudiana.

Wheat bread with sucrose content replaced with different levels of stevia extract was compared with traditional wheat bread. The ability to reduce glucose intake was highlighted by performing enzymatic assays using α-amylase and α-glucosidase. Antioxidant activity was measured by determining the scavenging effect on α,α-diphenyl-ß-picrylhydrazyl radical. In comparison with the control, the bread with stevia extract was softer and had lower microbial growth during the shelf-life study. The sensory test showed that the substitution of 50% stevia extract was more acceptable when comparing with all the quality characteristics. Regarding the nutritional contribution, the content of dietary fiber and digestible carbohydrates in the bread with stevia extract was higher and lower respectively, so caloric intake was significantly reduced. The results showed that the biological properties of Stevia rebaudiana extract were retained after the bread making process and that the proposed bread could be suitable as functional food in human nutrition.

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.

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 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.