Bioactive Compounds and Nanodelivery Perspectives for Treatment of Cardiovascular Diseases

Bioactive compounds are comprised of small quantities of extra nutritional constituents providing both health benefits and enhanced nutritional value, based on their ability to modulate one or more metabolic processes. Plant-based diets are being thoroughly researched for their cardiovascular properties and effectiveness against cancer. Flavonoids, phytoestrogens, phenolic compounds, and carotenoids are some of the bioactive compounds that aim to work in prevention and treating the cardiovascular disease in a systemic manner, including hypertension, atherosclerosis, and heart failure. Their antioxidant and anti-inflammatory properties are the most important characteristics that make them favorable candidates for CVDs treatment. However, their low water solubility and stability results in low bioavailability, limited accessibility, and poor absorption. The oral delivery of bioactive compounds is constrained due to physiological barriers such as the pH, mucus layer, gastrointestinal enzymes, epithelium, etc. The present review aims to revise the main bioactive compounds with a significant role in CVDs in terms of preventive, diagnostic, and treatment measures. The advantages of nanoformulations and novel multifunctional nanomaterials development are described in order to overcome multiple obstacles, including the physiological ones, by summarizing the most recent preclinical data and clinical trials reported in the literature. Nanotechnologies will open a new window in the area of CVDs with the opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues.

Immunonutritional Protease Inhibitors from T. durum and A. sativa Display Metabolic Similarities when Assayed on Human Macrophage-Like Cells

This study evaluated the immunonutritional effects caused by protease inhibitors from Avena sativa and Triticum durum to human macrophage-like cells. Macrophages were exposed (3 h) to extracts obtained from flours, and mitochondrial-associated oxygen consumption rates and inflammatory, metabolic, and proteome adaptations were quantified. Mass spectrometry ‘m/z’ signals of the extracts obtained from T. durum and A. sativa revealed molecular weights of 18–35 kDa and 16–22 kDa, respectively, for the compounds present at highest concentrations. Extracts from T. durum exhibited lower susceptibility to degradation by gastrointestinal enzymes than those from A. sativa: 9.5% vs. 20.2%. Despite their different botanical origin, both extracts increased TLR4 expression. Metabolic protein levels were indicative of a decreased glycolytic to lactate flux in cell cultures upon stimulation with A. sativa extracts, which improved mitochondrial respiration in relation to those from T. durum. Principal components analysis confirmed relative similarities between immune–metabolic events triggered by immunonutritional ingredients in T. durum and A. sativa. Collectively, immunonutritional effects help to interpret the differences between both crops, worsening or improving, macrophage immune reactivity (tolerogenicity), and better control of inflammatory processes.

In Vitro Assessment of Antioxidative Potential of Goat Milk, Casein and its Hydrolysates: Comparison of Goat Milk with Bovine and Buffalo milk

The present study was executed with an aim to explore the antioxidative potential of goat, cow, and buffalo milk. Buffalo milk has showed highest antioxidative potential than goat and cow milk as measured by ABTS, ORAC, and DPPH assays, whereas goat milk has showed better antioxidative potential than cow milk when measured by ORAC and DPPH. Further, the effect of temperature on the antioxidative potential of goat milk was assessed. An increase in temperature has a negatively affect the antioxidative potential of goat milk. The antioxidative potential of goat milk was in the following order: raw milk > pasteurized milk > boiled milk. Casein derived from goat milk by isoelectric precipitation was hydrolyzed by gastrointestinal enzymes pepsin (P), trypsin (T), chymotrypsin (C), and their combinations PT, PC, TC, and PTC. Among all the casein hydrolysates, the maximum antioxidative potential was found in PT hydrolysate, further fractionated by 10, 3 and 1 kDa ultrafiltration membranes. 3–10 kDa fraction exhibited maximum antioxidative potential in comparison to other fractions of PT hydrolysate. Our results suggested that antioxidative potential of goat milk and its hydrolysates could be an important mean to obtain natural antioxidative peptides.

Purification and Identification of Cholesterol Micelle Formation Inhibitory Peptides of Hydrolysate from High Hydrostatic Pressure-Assisted Protease Hydrolysis of Fermented Seabass Byproduct

This research focuses on the proteolytic capacity of sea bass byproduct (SB) and their hypocholesterolemic activity via the cholesterol micelle formation (CMF) inhibition. SB was fermented with seven mixed lactic acid bacteria for 5 h at 42 °C. The lactic fermented SB was hydrolyzed with Protease N for 6 h under HHP to obtain the SB hydrolysates (HHP-assisted Protease N hydrolysis after fermentation, F-HHP-PN6). The supernatant was separated from the SB hydrolysate and freeze-dried. As the hydrolysis time extended to 6 h, soluble protein content increased from 187.1 to 565.8 mg/g, and peptide content increased from 112.8 to 421.9 mg/g, while inhibition of CMF increased from 75.0% to 88.4%. Decreasing the CMF inhibitory activity from 88.4% to 42.1% by simulated gastrointestinal digestion (FHHP-PN6 was further hydrolyzed by gastrointestinal enzymes, F-HHP-PN6-PP) reduced the CMF inhibitory activity of F-HHP-PN6. Using gel filtration chromatography, the F-HHP-PN6-PP was fractioned into six fractions. The molecular weight of the fifth fraction from F-HHP-PN6-PP was between 340 and 290 Da, and the highest inhibitory efficiency ratio (IER) on CMF was 238.9%/mg/mL. Further purification and identification of new peptides with CMF inhibitory activity presented the peptide sequences in Ser-Ala-Gln, Pro-Trp, and Val-Gly-Gly-Thr; the IERs were 361.7, 3230.0, and 302.9%/mg/mL, respectively.

Proteases in the diet of monogastric animals

There are many proteases, and about 2% of the human genome is involved in the regulation of their formation. The share of proteases involved in digestion accounts for only a small part. Despite this, the mechanisms of action of digestive proteases are less studied than carbohydrases and lipases. The incorporation of exogenous proteases into young animal feeds is often accompanied by improved utilization of protein and other nutrients. Exogenous proteases degrade inhibitors of the endogenous protease and lectins in feed. Alkaline proteases are of interest due to their broader substrate specificity and activity throughout the entire gastrointestinal tract. This group includes keratinases, which digest proteins inaccessible for cleavage by proteases and peptidases of animals. Keratinases digest agglutinins, glycinin and b-conglycinin and connective tissue proteins, which are resistant to the action of gastrointestinal enzymes and a number of exogenous proteases. The alleged reasons for the inconsistent results when using feed proteases are described. Their mediated positive effects not associated with proteolysis are indicated. It is advisable to use proteases with keratinolytic activity as fodder proteases.

Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness

The chickpea (Cicer arietinum L.) is one of the most important pulses worldwide. The objective was to identify, compare and evaluate peptides from chickpea hydrolysates produced by two enzymatic treatments. The antidiabetic potential and bitterness of the peptides and induction of bitter receptors were identified in silico. Proteins were isolated from the Kabuli variety. Peptides were produced from the proteins using a simulated digestive system (pepsin/pancreatin, 1:50 Enzyme/Protein, E/P), and these peptides were compared with those produced via bromelain hydrolysis (1:50 E/P). The protein profiles, sequences and characteristics of the peptides were evaluated. The biochemical inhibition and molecular docking of dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase were also studied. The molecular docking identified peptides from enzymatic hydrolysis as inhibitors of DPP-IV. The high hydrophobicity of the peptides indicated the potential for bitterness. There was no correlation between peptide length and DPP-IV binding. Peptides sequenced from the pepsin/pancreatin hydrolysates, PHPATSGGGL and YVDGSGTPLT, had greater affinity for the DPP-IV catalytic site than the peptides from the bromelain hydrolysates. These results are in agreement with their biochemical inhibition, when considering the inhibition of sitagliptin (54.3 µg/mL) as a standard. The bitter receptors hTAS2R38, hTAS2R5, hTAS2R7 and hTAS2R14 were stimulated by most sequences, which could be beneficial in the treatment of type 2 diabetes. Chickpea hydrolysates could be utilized as functional ingredients to be included in the diet for the prevention of diabetes.

Influence of Sonication and Taraxacum Officinale Addition on the Antioxidant and Anti-ACE Activity of Protein Extracts from Sous Vide Beef Marinated with Sour Milk and after In Vitro Digestion

The present study assessed the effect of pretreating beef as a raw material for sous vide steak preparation. The pretreatment involved maceration of a batch of meat in sour milk with the simultaneous use of ultrasound (250 or 500 W) as well as the addition of Taraxacum officinale. The biological activity profile of the peptides was assessed in terms of their antioxidant activity and inhibiting activity against angiotensin-converting enzyme (ACE). Changes in the biological activity of peptides under the influence of hydrolysis by gastrointestinal enzymes, i.e., pepsin and pancreatin, were also considered. There was no significant effect of T. officinale addition and sonication of beef batches on the protein content (except for lot S6, after sonication at 500 W as acoustic power and with the addition of dandelion). It was observed that the interaction of maceration in sour milk with simultaneous ultrasound treatment as the initial production step of sous vide beef steak generates the formation of peptides with antioxidant properties. Moreover, peptide formation can be further enhanced by adding dandelion (based on the results of antiradical and chelating activity tests). In addition, the progression of hydrolysis under the influence of gastrointestinal enzymes promotes the release of peptides with antioxidant and anti-ACE activity.

1-Kestose supplementation mitigates the progressive deterioration of glucose metabolism in type 2 diabetes OLETF rats

The fructooligosaccharide 1-kestose cannot be hydrolyzed by gastrointestinal enzymes, and is instead fermented by the gut microbiota. Previous studies suggest that 1-kestose promotes increases in butyrate concentrations in vitro and in the ceca of rats. Low levels of butyrate-producing microbiota are frequently observed in the gut of patients and experimental animals with type 2 diabetes (T2D). However, little is known about the role of 1-kestose in increasing the butyrate-producing microbiota and improving the metabolic conditions in type 2 diabetic animals. Here, we demonstrate that supplementation with 1-kestose suppressed the development of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, possibly through improved glucose tolerance. We showed that the cecal contents of rats fed 1-kestose were high in butyrate and harbored a higher proportion of the butyrate-producing genus Anaerostipes compared to rats fed a control diet. These findings illustrate how 1-kestose modifications to the gut microbiota impact glucose metabolism of T2D, and provide a potential preventative strategy to control glucose metabolism associated with dysregulated insulin secretion.

Effect of replacing fish meal by full fat soybean meal on growth performance, feed utilization and gastrointestinal enzymes in diets for African catfish Clarias gariepinus

Study aimed to evaluate the effect of replacing fish meal with different levels of full fat soybean meal (FFSBM) on growth and digestive enzyme activities in the stomach, Liver and intestine for Clarias gariepinus. Four diets (D1, D2, D3 and D4) were formulated with 0, 15, 20 and 20 g 100-1 protein + DL-methionine by alternating FFSBM with fish meal. The growth of C. gariepinus was found to be significantly decreased when FFSBM replacement increased. Final body weight was 89.69, 79.70, 70.82 and 68.29 g for fish fed on D1, D2, D3 and D4, respectively, with significant differences between treatments. Specific growth rate (SGR) ranged between 3.11 to 2.78%. Proteolytic activity was higher only with alkaline pHs, whereas only very low activity was shown with acidic. Results of liver showed approximately similar results at acid and alkaline. In contrast, higher proteolytic activity in the stomach was observed at acid pHs 3.0 and 4.0 μg tyrosine-1 minute-1 mg-1 protein) whereas lower values were observed at neutral pH 7.0 g tyrosine-1 minute-1 mg-1 protein for catfish fed on the experimental diets. Moreover, trypsin activity was higher for the stomach, followed by the intestine and liver. However, higher amount of amylase observed in the liver than intestine and stomach.