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Food Chemistry Aug 2024Cabernet Sauvignon grape juice and wine underwent in vitro digestion, resulting in a reduction of most phenolic compounds (10%-100% decline), notably impacting...
Cabernet Sauvignon grape juice and wine underwent in vitro digestion, resulting in a reduction of most phenolic compounds (10%-100% decline), notably impacting anthocyanins (82%-100% decline) due to pH variations. However, specific phenolics, including p-hydroxybenzoic, protocatechuic, vanillic, p-coumaric, gallic and syringic acids, and coumarin esculetin, increased in concentration (10%-120%). Grape juice and wine samples showed comparable polyphenolic profile during all phases of digestion. Antioxidant activity persisted, and inhibition of angiotensin-I converting enzyme was improved after the digestion process, likely because of increased concentrations of listed phenolic acids and esculetin. Digested grape juice displayed comparable or superior bioactivity to red wine, indicating it as a promising source of accessible grape polyphenols for a broader audience. Nevertheless, Caco-2 cell model metabolization experiments revealed that only 3 of 42 analyzed compounds passed to the basolateral compartment, emphasizing the significant impact of digestion on polyphenol bioactivity, suggesting potential yet unmeasurable and overlooked implications for human health.
Topics: Wine; Humans; Vitis; Caco-2 Cells; Digestion; Fruit and Vegetable Juices; Phenols; Antioxidants; Polyphenols; Models, Biological
PubMed: 38604033
DOI: 10.1016/j.foodchem.2024.139228 -
American Journal of Physiology. Cell... Apr 2024Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and...
Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.
Topics: Humans; Angiotensin II; Dipeptidyl Peptidase 4; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Inflammation; Fibrosis; Cardiovascular Diseases; Angiotensin I
PubMed: 38581656
DOI: 10.1152/ajpcell.00734.2023 -
Heliyon Apr 2024In this research, we unveil the medical potential of pearls by identifying a novel bioactive peptide within them for the first time. The peptide, termed KKCHFWPFPW,...
In this research, we unveil the medical potential of pearls by identifying a novel bioactive peptide within them for the first time. The peptide, termed KKCHFWPFPW, emerges as a pioneering angiotensin I-converting enzyme (ACE) inhibitor, originating from the pearl matrix of . Employing quadrupole time-of-flight mass spectrometry, this peptide was meticulously selected and pinpointed. With a molecular weight of 1417.5 Da and a theoretical isoelectric point of 9.31, its inhibitory potency was demonstrated through a half-maximal inhibitory concentration (IC50) of 4.17 μM, established via high-performance liquid chromatography. The inhibition of ACE by this peptide was found to be competitive, as revealed by Lineweaver-Burk plot analysis, where an increase in peptide concentration correlated with an enhanced rate of ACE inhibition. To delve into the interaction between KKCHFWPFPW and ACE, molecular docking simulations were conducted using the Maestro 2022-1 Glide software, shedding light on the inhibitory mechanism. This investigation suggests that peptides derived from the pearl matrix hold promise as a novel source for antihypertensive agents.
PubMed: 38560194
DOI: 10.1016/j.heliyon.2024.e28060 -
Scientific Reports Mar 2024The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin...
The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.
Topics: Rats; Male; Animals; Quercetin; Renin; Catalase; Aldosterone; Rats, Sprague-Dawley; Reactive Oxygen Species; Hypoxia; Antioxidants; Oxidative Stress; Angiotensin I; Kidney
PubMed: 38556603
DOI: 10.1038/s41598-024-58134-3 -
International Journal of Biological... May 2024This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent...
A novel angiotensin I-converting enzyme inhibitory peptide from walnut (Juglans sigillata) protein hydrolysates and its evaluation in Ang II-induced HUVECs and hypertensive rats.
This study aims to seek angiotensin-I-converting enzyme inhibitory (ACEi) peptides from walnut using different enzymatic hydrolysis, and further to validate the potent ACEi peptides identified and screened via peptidomics and in silico analysis against hypertension in spontaneously hypertensive rats (SHRs). Results showed that walnut protein hydrolysate (WPH) prepared by combination of alcalase and simulated gastrointestinal digestion exhibited high ACEi activity. WPH was separated via Sephadex-G25, and four peptides were identified, screened and verified based on their PeptideRanker score, structural characteristic and ACE inhibition. Interestingly, FDWLR showed the highest ACEi activity with IC value of 8.02 μg/mL, which might be related to its close affinity with ACE observed in molecular docking. Subsequently, high absorption and non-toxicity of FDWLR was predicted via in silico absorption, distribution, metabolism, excretion and toxicity. Furthermore, FDWLR exhibited positively vasoregulation in Ang II-induced human umbilical vein endothelial cells, and great blood pressure lowering effect in SHRs.
Topics: Juglans; Animals; Angiotensin-Converting Enzyme Inhibitors; Humans; Human Umbilical Vein Endothelial Cells; Protein Hydrolysates; Rats; Rats, Inbred SHR; Hypertension; Molecular Docking Simulation; Angiotensin II; Peptides; Male; Peptidyl-Dipeptidase A; Antihypertensive Agents; Blood Pressure; Plant Proteins
PubMed: 38556230
DOI: 10.1016/j.ijbiomac.2024.131152 -
International Journal of Food Science 2024Tempe is an Indonesian food product traditionally obtained from soybeans through solid-state fermentation with . A variety of substrates can be processed into tempe in...
Tempe is an Indonesian food product traditionally obtained from soybeans through solid-state fermentation with . A variety of substrates can be processed into tempe in the presence of other microorganisms. In this study, grass pea seeds with the addition of flaxseed oil cake (20% w/w) were either fermented using individual mould strains-, , and -or cofermented with the moulds and . In the obtained products, the content of dietary fibre, B group vitamins, and the level of peptides and antioxidant potential in aqueous extracts were measured. Moreover, peptides, angiotensin I convertase inhibitor, and antioxidant activity were determined after digestion. The effect of digestates on the differentiation of enterocytes was also investigated. Fermentation generally resulted in a decrease in the dietary fibre, especially the insoluble fraction (30-50%). The product obtained with was the best source of riboflavin and thiamine among all tested. The fermentation process promoted the accumulation of water-soluble peptides and antioxidant compounds. After digestion, the largest amount of antioxidant and antiradical compounds was released from tempe obtained with . However, the enrichment of the products with antioxidants resulting from solid-state fermentation did not simply translate into an improvement in antioxidant potential after digestion. Generally, fermentation carried out in the presence of brought positive effects only in the case of DSM 1964. Digestion products obtained from tempe had a positive effect on the viability of Caco-2 cells differentiated into enterocytes. Interestingly, a higher activity of differentiation markers (alkaline phosphatase and sucrase-isomaltase) was observed under the influence of digestate of and tempe.
PubMed: 38549663
DOI: 10.1155/2024/5596798 -
Pharmaceuticals (Basel, Switzerland) Feb 2024Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol's isomers, and...
Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol's isomers, and flavonoids, among others. This study assessed the potential variance in the functional features presented by olive leaves from three different Portuguese cultivars-Cobrançosa, Madural, and Verdeal-randomly mix-cultivated in the geographical area of Vale de Salgueiros. Inorganic analysis determined their mineral profiles while an organic analysis measured their total phenolic and flavonoid content, and scanned their phenolic and tocopherol and fatty acid composition. The extracts' biological activity was tested by determining their antimicrobial and antioxidant power as well as their ability to inhibit acetylcholinesterase, butyrylcholinesterase, MAO-A/B, and angiotensin-I-converting enzyme. The inorganic profiles showed them to be an inexpensive source able to address different mineral deficiencies. All cultivars appear to have potential for use as possible antioxidants and future alternative antibiotics against some multidrug-resistant microorganisms, with caution regarding the arsenic content in the Verdeal cultivar. Madural's extract displayed properties to be considered a natural multitarget treatment for Alzheimer's and Parkinson's diseases, depression, and cardiometabolic and dual activity for blood pressure modulation. This work indicates that randomly cultivating different cultivars significantly modifies the leaves' composition while keeping their multifaceted therapeutic value.
PubMed: 38543060
DOI: 10.3390/ph17030274 -
Foods (Basel, Switzerland) Mar 2024The angiotensin-I converting enzyme (ACE) plays a pivotal role in hypertension, and while ACE inhibitors are conventional in hypertension management, synthetic...
The angiotensin-I converting enzyme (ACE) plays a pivotal role in hypertension, and while ACE inhibitors are conventional in hypertension management, synthetic medications often carry undesirable side effects. This has spurred interest in alternative ACE inhibitors derived from natural sources, such as edible insects. The silkworm, recognized for its bioactive peptides with potent ACE-inhibitory properties, has emerged as a promising candidate. This study aims to evaluate the acute toxicity and assess the antihypertensive efficacy of crude mature silkworm hydrolysate powder (MSHP) obtained from mature Thai silkworms. Utilizing the commercial protease Alcalase2.4L, MSHP was administered at various doses, including 50, 100, and 200 mg kg, to hypertensive rats. The investigation spans a 14-day period to observe any potential acute toxic effects. Results indicate that MSHP exhibits LD50 values equal to or exceeding 2000 mg kg, signifying a low level of acute toxicity. Furthermore, the effective dose for blood pressure reduction in hypertensive rats surpasses 100 mg kg of rat body weight. These findings suggest that MSHP derived from Thai mature silkworms holds promise as a natural antihypertensive food source. The implications of this research extend to the development of functional foods, functional ingredients, and dietary supplements aimed at managing hypertension.
PubMed: 38540933
DOI: 10.3390/foods13060943 -
Journal of Agricultural and Food... Apr 2024PepXLcMY-3, an X-prolyl dipeptidyl aminopeptidase derived from MY-3, was screened and recombinantly expressed in . The enzyme could exhibit about 40% activity within...
PepXLcMY-3, an X-prolyl dipeptidyl aminopeptidase derived from MY-3, was screened and recombinantly expressed in . The enzyme could exhibit about 40% activity within the pH range of 6.0-10. To further improve the pH robustness, site E396 located in the active pocket was discovered through alanine scanning. The mutant E396I displayed both developed activity and /. The optimal pH of E396I shifted from 6.0 to 10 compared to WT, with the relative activity within the pH range of 6.0-10 significantly increased. The site K648 was then proposed by semirational design. The activity of mutant E396I/K648D reached 4.03 U/mg. The optimal pH was restored to 6.0, and the pH stability was further improved. E396I/K648D could totally hydrolyze β-casomorphin 7 within 30 min. The hydrolysate showed 64.5% inhibition on angiotensin I converting enzyme, which was more efficient than those produced by E396I and WT, 23.2 and 44.7%, respectively.
Topics: Lactococcus lactis; Amino Acid Sequence; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Peptides; Hydrolases; Aminopeptidases; Hydrogen-Ion Concentration
PubMed: 38519413
DOI: 10.1021/acs.jafc.4c00146 -
Molecules (Basel, Switzerland) Mar 2024Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However,...
Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the protein (P) and had low IC values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of .
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Peptidyl-Dipeptidase A; Chromatography, Liquid; Reproducibility of Results; Tandem Mass Spectrometry; Peptides; Angiotensins
PubMed: 38474646
DOI: 10.3390/molecules29051134