Hydrolysates and peptides from chicken foot proteins to manage hypertension

La hipertensió arterial es considera un dels problemes de salut pública més importants en la nostra societat. El tractament d’aquesta patologia es basa en una combinació de canvis en l’estil de vida i tractament farmacològic. No obstant, per aquells pacients en fases de desenvolupament de la malaltia i que encara no necessiten tractament farmacològic, l’ús de nutricèutics o aliments funcionals amb propietats antihipertensives està rebent molta atenció ja que podria ser una bona estratègia per evitar el desenvolupament de la hipertensió. En aquest sentit, aquesta tesi té com a objectiu principal l’obtenció de pèptids antihipertensius a partir de la hidròlisi de proteïnes de pota de pollastre, un subproducte de la indústria avícola. Així, mitjançant la hidròlisi de la proteïnes de pota de pollastre sota condicions d’hidròlisi optimitzades es va obtenir un hidrolitzat, Hpp11, que mostrava efecte antihipertensiu després d’una administració aguda i crònica. L’hidrolitzat Hpp11 administrat agudament produïa l’efecte antihipertensiu mitjançant la reducció de l’activitat de l’enzim convertidor d’angiotensina, mentre que després d’una administració crònica, l’efecte antihipertensiu estava mediat per una millora en la funció endotelial. Addicionalment es van caracteritzar els pèptids presents en l’Hpp11 i dos d’ells, AVFQHNCQE i QVGPLIGRYCG van mostrar efecte antihipertensiu. En particular, el pèptid AVFQHNCQE no era absorbit i produïa el seu efecte antihipertensiu mitjançant la interacció amb receptors opioides presents en el tracte gastrointestinal. La interacció aquests receptors desencadenava un efecte antihipertensiu mediat pel vasodilatador òxid nítric, del qual se’n veia augmentada la seva biodisponibilitat gràcies a l’efecte antioxidant i de millora de la funció endotelial que també mostrava el pèptid. Els resultats d’aquesta tesi obren les portes a l’ús del l’hidrolitzat i dels pèptids antihipertensius obtinguts en aliments funcionals o nutricèutics que permetrien el control i prevenció del desenvolupament de la hipertensió.La hipertensión arterial se considera uno de los problemas de salud pública más importante de nuestra sociedad. El tratamiento de esta patología se basa en una combinación de cambios en el estilo de vida y tratamiento farmacológico. No obstante, para esos pacientes que se encuentran en fase de desarrollo de la enfermedad i que aún no requieren de tratamiento farmacológico, el uso de nutraceuticos o alimentos funcionales con propiedades antihipertensivas está recibiendo mucha atención ya que podrían ser una buena estrategia para evitar el desarrollo de la hipertensión. En este sentido, esta tesis tiene como objetivo principal la obtención de péptidos antihipertensivos a partir de la hidrólisis de proteínas de pata de pollo, un subproducto de la industria avícola. Así, mediante la hidrólisis de las proteínas de la pata de pollo bajo condiciones de hidrólisis optimizadas se obtuvo un hidrolizado, Hpp11, que mostró efecto antihipertensivo después de una administración aguda y crónica. El hidrolizado Hpp11 administrado agudamente producía el efecto antihipertensivo mediante la reducción de la actividad de la enzima convertidora de angiotensina, mientras que después de su administración crónica, el efecto antihipertensivo estaba mediado por una mejora en la función endotelial. Adicionalmente se caracterizaron los péptidos presentes en Hpp11 y dos de ellos AVFQHNCQE y QVGPLIGRYCG mostraron efecto antihipertensivo. En particular, el péptido AVFQHNCQE no era absorbido y producía su efecto antihipertensivo mediante la interacción con receptores opioides presentes en el tracto gastrointestinal. La interacción con estos receptores desencadenaba un efecto antihipertensivo mediado por el vasodilatador óxido nítrico, del cual se veía aumentada su biodisponibilidad gracias al efecto antioxidante y de mejora de la función endotelial que también mostró el péptido. Los resultados de esta tesis abren las puertas al uso del hidrolizado y de los péptidos antihipertensivos obtenidos en alimentos funcionales o nutraceuticos que permitirían el control y prevención del desarrollo el a hipertensión.Hypertension is considered one of the most important public health problems in our society. The treatment of this pathology is based on lifestyle modifications and pharmacology treatment. However, for those patients developing hypertension, whose blood pressure is not high enough to warrant pharmacology treatment, the use nutraceuticals or functional foods with antihypertensive properties have attracted considerable interest as good strategy to avoid the development of hypertension In this regard, this thesis aims to obtain antihypertensive peptides through the hydrolysis of chicken foot proteins, a by-product from poultry industries. Thus, through the hydrolysis of chicken foot proteins, it was obtained an hydrolysate, Hpp11, exerting antihypertensive effect after acute and chronic administration. Hpp11 administered acutely produced antihypertensive effect by reducing the activity of angiotensin converting enzyme, while when administered chronically the antihypertensive effect was mediated by an improvement in the endothelial function. Additionally the peptides contained in Hpp11 were characterised and two of them, AVFQHNCQE and QVGPLIGRYCG, showed antihypertensive effect. In particular, the peptide AVFQHNCQE was not absorbed and produced its antihypertensive effect through the interaction with opioid receptors from the gastrointestinal tract. The interaction with those receptors leaded to a nitric oxide-mediated antihypertensive effect. Moreover, the peptide contributed to enhance nitric oxide by exhibiting antioxidant effect and improving endothelial function. The results of this thesis open the doors to the use of the antihypertensive hydrolysate and peptides in functional foods or nutraceuticals for the control and prevention of hypertension

Evidence that Nitric Oxide is Involved in the Blood Pressure Lowering Effect of the Peptide AVFQHNCQE in Spontaneously Hypertensive Rats

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17–20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post administration, animals of both groups were intra peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties

The Catalan Surveillance Network of SARS-CoV-2 in Sewage: design, implementation, and performance

Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20-March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.The authors wish to thank the staff from all the WWTPs monitored for their help and technical support during the sampling campaigns. The authors acknowledge the funding received from the ACA and the ASPCAT from the Catalan Government (Generalitat de Catalunya). ICRA authors acknowledge the funding provided by the Generalitat de Catalunya through the Consolidated Research Group grants ICRA-ENV 2017 SGR 1124 and ICRA-TiA 2017 SGR 1318. ICRA researchers also thank the funding from the CERCA program of the Catalan Government.Peer reviewe

Novel Antihypertensive Peptides Derived from Chicken Foot Proteins

Contains fulltext : 205038.pdf (publisher's version ) (Open Access

LONG-TERM ADMINISTRATION OF GALLIC ACID DECREASES BLOOD PRESSURE IN METABOLIC SYNDROME ANIMAL MODEL VIA AN IMPROVEMENT OF ENDOTHELIAL FUNCTION

Gallic acid (GA, 3,4,5-trihidroxibenzoic) is a phenolic compound, widely represented in the plant kingdom, which has been demonstrated to exert beneficial health effects, including antihypertensive effect . The aim of this study was to evaluate the chronic antihypertensive effect of GA in hypertensive cafeteria diet-fed rats and the mechanisms involved in this effect. After 8 weeks of cafeteria diet feeding, male Wistar rats (n=6 per group) were daily orally supplemented with GA (6.65 mg/kg), Captopril (50 mg/kg) as a positive control or vehicle as a negative control for 3 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by the tail cuff method and thoracic aorta was extracted to evaluate endothelium-dependent genes expression. After 3 weeks of GA administration, there was a significant reduction in blood pressure (BP) (-20 mmHg decrement of SBP and -15 mmHg decrement on DBP) when compared to animals from the vehicle group. Regarding gene expression, GA produced the upregulation of Sirt-1 and eNOS gene expression resulting in an increase of NO production and promoting a vasodilatation effect. In addition, GA downregulated the gene expression of the vasoconstrictor agent, ET-1, which could contribute to BP reduction observed after GA administration. Moreover, the antihypertensive effect of GA could be explained through the overexpression of NOX4 which has been reported to exert vasoprotective effects. Considering these results, we can conclude that GA had chronic antihypertensive effect in cafeteria diet-fed rats through an improvement in the endothelial function

Dose-Related Antihypertensive Properties and the Corresponding Mechanisms of a Chicken Foot Hydrolysate in Hypertensive Rats

The antihypertensive properties of different doses of a chicken foot hydrolysate, Hpp11 and the mechanisms involved in this effect were investigated. Spontaneously hypertensive rats (SHR) were administered water, Captopril (50 mg/kg) or Hpp11 at different doses (25, 55 and 85 mg/kg), and the systolic blood pressure (SBP) was recorded. The SBP of normotensive Wistar-Kyoto (WKY) rats administered water or Hpp11 was also recorded. Additionally, plasmatic angiotensin-converting enzyme (ACE) activity was determined in the SHR administered Hpp11. Moreover, the relaxation caused by Hpp11 in isolated aortic rings from Sprague-Dawley rats was evaluated. Hpp11 exhibited antihypertensive activity at doses of 55 and 85 mg/kg, with maximum activity 6 h post-administration. At this time, no differences were found between these doses and Captopril. Initial SBP values of 55 and 85 mg/kg were recovered 24 or 8 h post-administration, respectively, 55 mg/kg being the most effective dose. At this dose, a reduction in the plasmatic ACE activity in the SHR was found. However, Hpp11 did not relax the aortic ring preparations. Therefore, ACE inhibition could be the mechanism underlying Hpp11 antihypertensive effect. Remarkably, Hpp11 did not modify SBP in WKY rats, showing that the decreased SBP effect is specific to the hypertensive state

Optimization of a polyphenol extraction method for sweet orange pulp (Citrus sinensis L.) to identify phenolic compounds consumed from sweet oranges.

The consumption of sweet oranges has been linked to several health benefits, many of which are attributed to hesperidin, a flavanone that is present in high amounts in these fruits. However, other phenolic compounds can contribute to the bioactivity of sweet orange. To link those effects to their phenolic profile, the complete characterization of the phenolic profile is mandatory. Although many studies have profiled the phenolic composition of orange juices, their pulps, which retain phenolic compounds, are overlooked. This fact is particularly relevant because dietary guidelines recommend the consumption of whole fruits. Therefore, this study aimed to develop a specific method for the optimal extraction of phenolics from orange pulp and to use this method to characterize these fruits grown at different locations by HPLC-ESI-MS/MS. The extraction conditions that reported the highest total polyphenol content (TPC) and hesperidin contents were 20 mL/g, 55 °C, and 90% methanol. The extraction time and number of sequential steps were further evaluated and optimized as 20 min and two extraction steps, respectively. Although lower extraction rates were achieved when using ethanol as the extraction solvent, high TPC and hesperidin yields were obtained, suggesting the potential use of this methodology to produce phenolic-rich extracts for the food industry. By applying the optimized methodology and analyzing the extracts by HPLC-ESI-MS/MS, geographic cultivation regions were demonstrated to affect the phenolic profiles of oranges. In short, we developed a quick, easy-to-perform methodology that can be used to extract orange phenolics from pulp for their identification and quantification and to evaluate the factors that affect the phenolic profile in sweet orange pulps

Dose-Related Antihypertensive Properties and the Corresponding Mechanisms of a Chicken Foot Hydrolysate in Hypertensive Rats

The antihypertensive properties of different doses of a chicken foot hydrolysate, Hpp11 and the mechanisms involved in this effect were investigated. Spontaneously hypertensive rats (SHR) were administered water, Captopril (50 mg/kg) or Hpp11 at different doses (25, 55 and 85 mg/kg), and the systolic blood pressure (SBP) was recorded. The SBP of normotensive Wistar-Kyoto (WKY) rats administered water or Hpp11 was also recorded. Additionally, plasmatic angiotensin-converting enzyme (ACE) activity was determined in the SHR administered Hpp11. Moreover, the relaxation caused by Hpp11 in isolated aortic rings from Sprague-Dawley rats was evaluated. Hpp11 exhibited antihypertensive activity at doses of 55 and 85 mg/kg, with maximum activity 6 h post-administration. At this time, no differences were found between these doses and Captopril. Initial SBP values of 55 and 85 mg/kg were recovered 24 or 8 h post-administration, respectively, 55 mg/kg being the most effective dose. At this dose, a reduction in the plasmatic ACE activity in the SHR was found. However, Hpp11 did not relax the aortic ring preparations. Therefore, ACE inhibition could be the mechanism underlying Hpp11 antihypertensive effect. Remarkably, Hpp11 did not modify SBP in WKY rats, showing that the decreased SBP effect is specific to the hypertensive state