Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

Is medical management useful in Moyamoya disease?

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

Process optimization,texture and microstructure of novel kelp tofu

Laminaria japonica Aresch as an edible and medicine dual-purpose marine algae,has been gradually accepted by people.Tofu was Chinese traditional food,combining kelp function ingredients with tofu has practical value.The extraction-optimization methodology and the sequences of kelp antihypertensive peptide(KAP)were investigated.The sensory,whiteness,water retention ability(WRA)and microstructure of KAP tofu were evaluated.The scanning electron microscope(SEM)results showed KAP addition(20%)significantly improved the tofu texture,with a denser network composed of relatively even pores.Compared with gypsum tofu and glucose-δ-interior fat(GDL)tofu,KAP tofu had significantly higher WRA(94.49±0.49)%and sensory evaluation score value(92.54±0.52),and a significantly lower IC_(50) value at(2.06±0.04)mg/mL(P<0.05).The maximum IC_(50) value(4.14 mg/mL)of kelp enzymatic hydrolysate was observed at enzyme(at an alkaline protease:trypsin ratio of 2:1)concentration 1.5%,temperature 55℃ and time 2 h.The sequences of 8 identified peptides were Lys-Tyr,Phe-Tyr,Gly-Lys-Tyr,Ala-Lys-Tyr,Ser-Lys-Thr-Tyr,Lys-Lys-Phe-Tyr,Lys-Phe-Lys-Tyr and Ala-Lys-Tyr-Ser-Tyr with IC_(50) values of 5.24,4.83,7.94,7.52,20.63,15.33,10.73 and 2.42μmol/L,respectively.These results indicated the potential use of KAP tofu as a valuable resource for development of functional foods.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Assessment of the Level of Metal(loid)s Pollution and Bioactive Compounds Screening of Anthill Soil

The anthill soil is used by hypertensive elderly and teenagers from Oshikoto region (Namibia) and many of them testified stabilization of their blood pressure to normal after consuming the anthill soil-derived aqueous extracts. This study therefore investigated and/or assessed the physicochemical parameters, the contents of some metal(loid)s (and their associated potential health risks) and the qualitative composition of bioactive compounds of this anthill soil. The homogenous soil sample collected from various anthill soils in the Oshikoto region was used to obtain the measurements of physiochemical parameters. The elemental contents were determined (using an Inductively Coupled Plasma Optical Emission Spectrophotometer) after acid digestion in accordance with the EPA method 350B and their potential health risk assessments were performed. Methanol, aqueous methanol, and aqueous-based extracts were generated via maceration extraction process prior to the screening of bioactive compounds using standard diagnostic assays. The oxidation reduction potential (164.4 ± 16.6 mV) was the only physicochemical parameter whose value was within the World Health Organization limits for drinking water whereas, total dissolved solids (23 ± 5.5 mg/L), electrical conductivity (44 ± 10.1 uS/cm) and pH (5.35 ± 0.33) were out of specifications. Phenolic compounds, flavonoids, terpenoids, and cardiac glycosides were present in anthill soil (with respect to the extractants used) to which its antihypertensive properties can be attributed in addition to some of the studied mineral components. With respect to the pH, TDS and EC, and the contents of most metal(loid)s in relation to their health risk assessment values, the results suggest that aqueous extracts derived from this anthill soil can be deemed unsuitable for human consumption.

Synthesis of 2-Substituted Benzimidazol-N-biphenyl Acid and Crystal Structure of 4'-[(2-n-Propyl-1H-benzimidazol-1-yl)methyl] Biphenyl-2-carboxylate Acid

Nine analogues of telmisartan, 2-substituted benzimidazol-N-biphenyl acid, were designed and synthesized, from substituted benzimidazoles reacted with methyl 4'-(bromomethyl)- -biphenyl-2-carboxylate, then hydrolysis with KOH in MeOH and H2O. Their structures were confirmed by IR, 'H NMR, MS spectroscopy and elemental analysis. The crystal structure of 4'-[(2-n-propyl-1H-benzimidazol-lyl) methyl] biphenyl-2-carboxylic acid was determined by single crystal X-ray diffraction.

Antihypertensive drugs and glucose metabolism

Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

Non-interventional management of resistant hypertension

Hypertension is one of the most popular fields of re-search in modern medicine due to its high prevalence and its major impact on cardiovascular risk and con-sequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the "uncontrollable" part of arterial hy-pertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. As-pects like the exact prevalence and prognosis are yet tobe clarified. In an effort to manage patients with resis-tant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hyper-tension and provide practical recommendations for cli-nicians dealing with such patients.

Antihypertensive Properties on Spontaneously Hypertensive Rats of Peptide Hydrolysates from Silkworm Pupae Protein

Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.

Effect of morin, a flavonoid against DOCA-salt hypertensive rats:a dose dependent study

Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA(25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues.Results:DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure,serum hepatic marker enzyme activities such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and gamma-glutamyl transpeptidase(GGT)and renal function markers(urea, uric acid and creatinine) in plasma. Oral administration of morin(25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level.Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses(25 and 75 mg/kg bw).Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.

Plants Used as Antihypertensive

Hypertension is a critical health problem and worse other cardiovascular diseases.It is mainly of two types:Primary or essential hypertension and Secondary hypertension.Hypertension is the primary possibility feature for coronary heart disease,stroke and renal vascular disease.Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects.Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms,from the bottom of cell culture and ex-vivo tissue data.According to WHO,natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body.Plants are the regular industrial units for the invention of chemical constituents,they used as immunity booster to enhance the natural capacity of the body to fight against different health prob-lems as well as herbal medicines and food products also.Eighty percent population of the world(around 5.6 billion people)consume medicines from natural plants for major health concerns.This review provides a bird’s eye analysis primarily on the traditional utilization,phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.Hibiscus sabdariffa,Allium sativum,Andrographis paniculata,Apium graveolens,Bidenspilosa,Camel-lia sinensis,Coptis chinensis,Coriandrum sativum,Crataegus spp.,Crocus sativus,Cymbopogon citrates,Nigella sativa,Panax ginseng,Salviaemiltiorrhizae,Zingiber officinale,Tribulus terrestris,Rauwolfiaserpentina,Terminalia arjuna etc.

Factors associated with intensification of antihypertensive drug therapy in patients with poorly controlled hypertension

Objective To assess antihypertensive management of older patients with poor blood pressure(BP)control.Methods Physicians,voluntary participating in the study,included six consecutive hypertensive patients during routine visits.Hypertension had to have been previously recognized and averaged office BP was>140 and/or>90 mmHg in spite of>6 weeks of antihypertensive therapy.The physicians completed a questionnaire on patients'history of cardiovascular(CV)risk factors,comorbidities,home BP monitoring,anthropometric data and the pharmacotherapy.Results Mean age of the 6462 patients was 61 years,7%were>80 years,51%were female.Mean士SD office BP values were 158士13/92土10 mmHg.The most commonly prescribed antihypertensive drugs were:diuretics(67%),ACE inhibitors(64%),calcium channel blockers(58%)and卩-blockers(54%),and their use increased with age.On monotherapy or dual therapy,43%of the patients and 40%had their latest treatment modification within six months.Home BP monitoring was a factor that accelerated the modification of the therapy.Older patients had to have less chance on faster modification of antihypertensive therapy in spite of presence of diabetes and higher systolic BP.Conclusions Our study suggests that a large number of outpatients with poor BP control receive suboptimal antihypertensive therapy,especially in primary care.In older patients,higher BP values in the office settings are more frequently accepted by physicians even in case of higher CV risk.Regular home BP monitoring hastens the decision to intensify of antihypertensive treatment.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.

Angiotensin I converting enzyme(ACE)inhibitory activity and antihypertensive effects of rice peptides

In this paper,the antihypertension effect of rice peptide(RP)was studied.With spontaneously hypertensive rats(SHR)and Wistar Kyoto(WKY)as the research objects,RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure(SBP)was measured.At the end of the long-term gastric irrigation experiment,the content of nitric oxide(NO),angiotensin-converting enzyme(ACE),angiotensin II(Ang II)and renin in the plasma and the activity of ACE were determined.The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP signifi cantly reduced systolic pressure by 24.6 and 17.2 mm Hg,respectively after a single and long-term gastric irrigation test.RP also could inhibit the activity of ACE and increase the release of NO.These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system(RAS)and NO.

Synchronized separation of atorvastatin——an antihyperlipidemic drug with antihypertensive, antidiabetic, antithrombotic drugs by RP-LC for determination in combined formulations

A new rapid and sensitive high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of atorvastatin—an antihyperlipidemic drug along with most commonly prescribed drugs (antihyperlipidemic, antihypertensive, antidiabetic, antithrombotic) in bulk and marketed combined formulations. The chromatographic separation was carried out by gradient elution mode with acetonitrile as organic modifier and 0.1% triethylamine acetate (TEAA) buffer pH 5 at a flow rate of 1 mL/min and a diode array detector at wavelength 230 nm was employed for detection of the analytes. Calibration curves were linear in the range of 5-150 mg/mL for all the drugs with correlation coefficients of determination (r 2 values)Z0.999. Limits of detection (LODs) and Limits of quantification (LOQs) ranged from 0.1 to 0.27 mg/mL and 0.3 to 0.89 mg/mL respectively. Intra-day and inter-day precision was studied at three concentration levels (20, 60 and 100 mg/mL). The intra-day and inter-day RSD for all compounds was less than 2.0%. The accuracy for all compounds was found to be between 98% and 102%. Thus, the performance of the method described allows its use in quantification of atorvastatin along with 9 most commonly prescribed drugs available in market as atorvastatin combined dosage forms.

抗高血压中草药罗布麻NO释放作用的内皮保护作用和机制(英文)

OBJECTIVE The extracts of the Apocynum venetumleaves(AVLE),also known as Luobuma,is an antihypertensive medicinal herb used widely in TCM.AVLE has been reported to exert antihypertensive action by dilating the blood vessels in an endothelium-dependent and concentration-dependent manner with optimal effect seen at as low as 10μg·mL.The present study seeks to further evaluate the free radical scavenging actions and cellular mechanism underlying the nitric oxide(NO)-releasing property of AVLE in rat aorta and human umbilical vein endothelial cells(HUVECs).METHODS Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of NG-nitro-L-arginine(LNAME,100μmol·L-1),endothelial NO synthase inhibitor(eNOS),ODQ(1μmol·L-1),soluble guanylyl cyclase inhibitor,polyethyleneglycol catalase(PP2,20μmol·L-1),inhibitor of Src kinase and wortmannin(30nmol·L-1),and LY294002(20μmol·L-1),PI3-Kinase inhibitor.Total nitrite and nitrate(NOx)level were measured by Greiss reagent.The cellular effects of AVLE was tested in HUVECs at different concentration with or without inhibitors.The phosphorylation level of Akt and eNOS were assessed by Western blotting.RESULTS In the rat aorta,AVLE(0.3-10μg·mL-1)dose-dependently inhibited the contraction to phenylephrine(1μmol·L-1)and significantly suppressed theβ-NADPH-induced generation of superoxide anion(SOA).Removal of endothelium,treatment with L-NAME or ODQ prevented the vasorelaxant effects of AVLE.Similarly,pre-treatment with PP2,wortmannin and LY294002 reduced the vasorelaxant effects of AVLE.AVLE significantly increased of total NOx level in rat aorta compared to control.It also caused phosphorylation of AKT and eNOS in cultured HUVECs in a dose-dependent manner and which were markedly suppressed by PP2,wortmannin and LY294002.CONCLUSION The present results suggest that the vasorelaxant effect of AVLE is due to its dual ability of releasing NO and protecting it from the scavenging actions of the SOA.Furthermore,AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway.

<i>In Vitro</i>Antioxidative Activity and Antihypertensive Activity of Soy Sauce Cake Derived from the Manufacturing of Japanese Style Fermented Soy Sauce

As the manufacture of soy sauce produces a large quantity of soy sauce cake as one of food processing waste, it is necessary to search for possible ways for their utilization. Chemical composition of soy sauce cake was analyzed to use as a material of high-value functional ingredients. The results showed that soy sauce cake could be potentially used as functional ingredients rich in proteins, with high antioxidative activitiy, free radical scavenging activity, and antihypertensive activity. Based on their IC50 values, the hydrolysates from soy sauce cake were more significantly effective against superoxide anion radicals and ACE, compared with hydroxyl radicals and DPPH radicals. The present study indicates that a large amount of soy sauce cake can be used as source of proteins with good antioxidative activity, free radical scavenging activity, and antihypertensive activity. The utilization of soy sauce cake may be also to contribute to reduce food processing wastes and to resolve an environmental problem.

Interaction mechanism of egg white-derived ACE inhibitory peptide TNGIIR with ACE and its effect on the expression of ACE and AT1 receptor

The egg white-derived hexapeptide TNGIIR inhibits angiotensin-converting enzyme(ACE)activity in vitro.In this work,molecular docking revealed that TNGIIR established hydrogen bonds with the S1(Ala 354),S2(Gln 281,His 513,Tyr 520 and Lys 511)and S1(Glu 162)pockets of ACE.In addition,the potential antihypertensive effect of the oral administration of TNGIIR in spontaneously hypertensive rats(SHR)was investigated,as was the effect of this peptide on the mRNA expression of ACE and angiotensin type 1(AT1)and type 2(AT2)receptors in renal tissue.The oral administration of TNGIIR(2,10 and 50 mg/kg)for up to four weeks did not reduce the blood pressure of SHR,in contrast to captopril(10 mg/kg,orally),but attenuated the mRNA expression of ACE and AT1 receptor(as did captopril).In contrast,both TNGIIR and captopril enhanced the expression of AT2 receptor mRNA.There was no change in the circulating concentration of angiotensin I,but a slight decrease(about 10%)was seen in the concentration of circulating angiotensin II with TNGIIR and captopril.

Medications in type-2 diabetics and their association with liver fibrosis

BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.