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1.
《Cereal Chemistry》2017,94(1):117-123
The objective of this study was to evaluate the antihypertensive potential of common bean protein hydrolysate. Protein concentrates were obtained, followed by Alcalase enzymatic hydrolysis, and then ultrafiltrated (3,000 molecular weight cutoff); the lyophilized product was named BP3. The angiotensin converting enzyme (ACE) inhibitory activity was determined as IC50 (3.68 ± 0.07 μg/mL). The antihypertensive effect was evaluated in spontaneously hypertensive rats (SHR) by two assays; Captopril ACE inhibitor was used as a reference compound and water as a control. A short‐term assay showed a maximum decrease in mean arterial pressure of –41 ± 5 mmHg in SHR, 3 h after oral administration of 500 mg of BP3/kg of body weight (bw). In a long‐term assay, a significant decrease in systolic blood pressure of –24 ± 5 mmHg was observed in SHR, after 45 days of oral administration of 500 mg of BP3/kg of bw/12 h. In both assays, BP3 treatment showed antihypertensive effect over SHR, similar to Captopril treatment. The sequences of the most abundant peptides present in BP3, determined by mass spectrometry, were identified as KFPWVK, GADFRKK, and PQSPCKRVNRHS. These peptides are reported for the first time in Azufrado Higuera common beans, and they are most likely responsible for the antihypertensive effect of BP3.  相似文献   

2.
Antihypertensive properties of spinach leaf protein digests   总被引:5,自引:0,他引:5  
Leaf protein containing approximately 50% rubisco (ribulose bisphosphate carboxylase/oxygenase) was obtained from fresh spinach leaf with the use of a simple extraction method. Pepsin and pepsin-pancreatin digests of spinach leaf protein have potent angiotensin-I converting enzyme inhibitory properties with IC(50) values of 56 and 120 microg/mL, respectively. Both digests of leaf protein have antihypertensive effects after oral administration to spontaneously hypertensive rats (SHR) with minimum effective doses of 0.25 and 0.5 g/kg, respectively. The maximum antihypertensive effect for the pepsin digest was observed 4 h after oral administration, while for the pepsin-pancreatin digest, the maximum effect was observed 2 h after oral administration. Undigested spinach leaf protein did not exert any significant antihypertensive effect after oral administration to SHR at doses of 0.5 and 1 g/kg. Obtained results show that the pepsin digest of leaf protein may be useful in treatment of hypertension.  相似文献   

3.
In the search for novel peptides that inhibit the angiotensin I-converting enzyme (ACE), porcine skeletal troponin was hydrolyzed with pepsin, and the products were subjected to various types of chromatography to isolate active peptides. Glu-Lys-Glu-Arg-Glu-Arg-Gln (EKERERQ) and Lys-Arg-Gln-Lys-Tyr-Asp-Ile (KRQKYDI) were identified as active peptides, and their 50% inhibitory concentrations were found to be 552.5 and 26.2 microM, respectively. These are novel ACE inhibitory peptides, and the activity of KRQKYDI was the strongest among previously reported troponin-originated peptides. KRQKYDI was slowly hydrolyzed by treatment with ACE, and kinetic studies indicated that this peptide was a competitive inhibitor of the enzyme. When KRQKYDI was administered orally to spontaneously hypertensive rats (SHR) at a dose of 10 mg/kg, a temporary antihypertensive activity was observed at 3 and 6 h after administration.  相似文献   

4.
Corn gluten meal (CGM) was hydrolyzed by Alcalase after starch removal of CGM was applied as a pretreatment. A new inhibitory peptide for angiotensin I-converting enzyme (ACE) was isolated from the hydrolysate of CGM with the use of Bio-Rad P-2 gel filtration and followed by reverse-phase high-performance liquid chromatography (RP-HPLC). The sequence of the active peptide was determined to be Ala-Tyr after the application of amino acid analysis and HPLC/MS. The IC50 of the peptide was 14.2 microM, and it was not affected by preincubation with 30 mU of ACE at 37 degrees C for 3 h. Ala-Tyr also exerted antihypertensive effects after oral administration to spontaneously hypertensive rats. A maximal reduction of systolic blood pressure of 9.5 mmHg was observed 2 h after oral administration of Ala-Tyr at doses of 50 mg/kg.  相似文献   

5.
Food-derived bioactive peptides with ACE-inhibitory properties are receiving special attention due to their beneficial effects in the treatment of hypertension. In this work we evaluate the impact of a simulated gastrointestinal digestion on the stability and activity of two bioactive peptides that derive from ovalbumin by enzymatic hydrolysis, YAEERYPIL and RADHPFL. These peptides possess in vitro ACE-inhibitory activity and antihypertensive activity in spontaneously hypertensive rats (SHR). The results showed that YAEERYPIL and RADHPFL were susceptible to proteolytic degradation after incubation with pepsin and a pancreatic extract. In addition, their ACE-inhibitory activity in vitro decreased after the simulated digestion. The antihypertensive activity on SHR of the end products of the gastrointestinal hydrolysis, YAEER, YPI, and RADHP, was evaluated. The fragments YPI and RADHP significantly decreased blood pressure, 2 h after administration, at doses of 2 mg/kg, but they probably did not exert their antihypertensive effect through an ACE-inhibitory mechanism. It is likely that RADHP is also the active end product of the gastrointestinal digestion of the antihypertensive peptides FRADHPFL (ovokinin) and RADHPF (ovokinin 2-7).  相似文献   

6.
Angiotensin I converting enzyme (ACE) inhibitory peptide was isolated from tuna dark muscle hydrolysate prepared by alcalase, neutrase, pepsin, papain, alpha-chymotrypsin, and trypsin, respectively. Among hydrolysates, the pepsin-derived hydrolysate exhibited the highest ACE I inhibitory activity versus those of other enzyme hydrolysates. The structure of the peptide was identified to be Trp-Pro-Glu-Ala-Ala-Glu-Leu-Met-Met-Glu-Val-Asp-Pro (molecular weight 1581 Da) by time of flight mass spectrometry/mass spectrometry analysis, and the IC 50 value of the peptide was 21.6 microM. The Lineweaver-Burk plots revealed that the peptide acts as a noncompetitive inhibitor, and the inhibitor constant ( K i) was calculated as 26.6 microM using the secondary plots. The peptide had an antihypertensive effect according to the time-course measurement after oral administration to spontaneously hypertensive rats. Maximal reduction was detected 3 h after oral administration at a dose of 10 mg/kg of body weight. These results suggest that the peptide derived from tuna dark muscle would be a beneficial ingredient for functional food or pharmaceuticals against hypertension and its related diseases.  相似文献   

7.
Seven kinds of angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from the hydrolysates of wakame (Undaria pinnatifida) by Protease S "Amano" (from Bacillus stearothermophilus) by using three-step high-performance liquid chromatography (HPLC) on a reverse-phase column. These peptides were identified by amino acid composition analysis, sequence analysis, and liquid chromatography-mass spectrometry (LC-MS), as Val-Tyr (IC(50) = 35.2 microM), Ile-Tyr (6.1 microM), Ala-Trp (18.8 microM), Phe-Tyr (42.3 microM), Val-Trp (3.3 microM), Ile-Trp (1.5 microM), and Leu-Trp (23.6 microM). These peptides have resistance against gastrointestinal proteases in vitro. Each peptide was determined to have an antihypertensive effect after a single oral administration in spontaneously hypertensive rats (SHR). Among them, the blood pressure significantly decreased by Val-Tyr, Ile-Tyr, Phe-Tyr, and Ile-Trp in a dose of 1 mg/kg of body weight (BW). The present study showed that antihypertensive effect in the hydrolysates of wakame by Protease S "Amano" was attributed to these peptides.  相似文献   

8.
Angiotensin converting enzyme (ACE) inhibitory peptides prepared from soy protein by the action of alcalase enzyme was tested for its hypotensive effect on spontaneously hypertensive rats (SHR). Captopril, an ACE inhibitor used widely for hypertension treatment, was also applied in comparison. A significant (p < 0.05) decrease in systolic blood pressure of SHR was observed when soy ACE inhibitory peptides were orally administrated at three different dose levels (100, 500, and 1000 mg/kg of body weight/day), whereas little change occurred in the blood pressure of normotensive rats even at the highest dose. After a month-long feeding, blood pressure readings of SHR fell by approximately 38 mmHg from the original level at the lowest dose; a steadily and progressively hypotensive effect existed for these soy ACE inhibitory peptides administration groups. An obvious fluctuation was observed at the third week, although Captopril had a stronger hypotensive effect. The ACE activity of serum, aorta and lung, and lipid content of serum of SHR upon administration of soy ACE inhibitory peptides did not show a significant difference from that of the control group, whereas the serum ACE activity increased and the aorta ACE activity decreased significantly (p < 0.05) for the Captopril group. Serum Na(+) concentration decreased significantly in both the peptides-treated groups and the Captopril-treated group in comparison with the control group, whereas no lowering effect was observed for serum K(+) and serum Ca(2+) concentrations. These results suggested that the hypotensive effect of ACE inhibitory peptides derived from soy protein could be at least partly attributed to the action on salt/water balance.  相似文献   

9.
Disposition kinetic behavior and metabolism studies of metamitron and its metabolite in terms of the parent compound were carried out in black Bengal goats after a single oral administration of a nontoxic oral dose at 30 mg kg(-1) of body weight. Metamitron was detected in the blood sample at 5 min (2.23 +/- 0.04 microg mL(-1)), maximum at 1 h (3.43 +/- 0.02 microg mL(-1)) and minimum at 12 h (0.41 +/- 0.01 microg mL(-1)), after a single oral administration. Metabolite [3-methyl-6-phenyl-1,2,4-triazin-5(4H)-one] in terms of the parent compound was detected in the blood sample at 5 min (0.47 +/- 0.006 microg mL(-1)), maximum at 6 h (5.12 +/- 0.02 microg mL(-1)) and minimum at 96 h (1.06 +/- 0.016 microg mL(-1)), after a single oral administration. The t(1/2 K) and Cl(B) values of metamitron were 3.63 +/- 0.05 h and 1.36 +/- 0.016 L kg(-1) h(-1), respectively, whereas the t(1/2K)(m) and Cl(B)(m) values of the metabolite were 38.15 +/- 0.37 h and 0.091 +/- 0.001 L kg(-1) h(-1), respectively, which suggested long persistence of the metabolite in blood and tissues of goat. Metamitron was excreted through feces and urine for up to 48 and 72 h, whereas the metabolite was excreted for up to 168 and 144 h, respectively. Metabolite alone contributed to 96 and 67% of combined recovery percentage of metamitron and metabolite against the administered dose in feces and urine of goat, respectively. All of the goat tissues except lung, adrenal gland, ovary, testis, and mammary gland retained the metabolite residue for up to 6 days after administration.  相似文献   

10.
As a folk medicine, the hot-water infusion of water caltrop fruits has been used to protect the liver. In this study, the outer skins of mature water caltrop fruits ( Trapa taiwanensis Nakai) were removed, forced-air-dried, pulverized, and subjected to extraction with hot water, and the infusion was lyophilized and pulverized to prepare a hot water extract of T. taiwanensis (HWETT). HWETT was subjected to assays of α,α-diphenyl-β-picrylhydrazyl scavenging activity, reducing power, Trolox equivalent antioxidant capacity, and antioxidative potency, and all determinations showed HWETT to be a potent antioxidant. As further analyzed with LC-MS, two major HPLC-detected components were elucidated as gallic acid and ellagic acid. Hepatoprotective activity of HWETT was assessed with Sprague-Dawley male rats by oral administration. Six groups of rats (n = 8 for each) were respectively treated, namely, control, CCl(4) (20% CCl(4)/olive oil by 2.0 mL/kg bw), CCl(4) and Silymarin (200 mg/kg bw), CCl(4) and low HWETT dose (12.5 mg/kg bw), CCl(4) and medium HWETT dose (25 mg/kg bw), and CCl(4) and high HWETT dose (125 mg/kg bw). After 8 weeks, all animals were fasted for an additional day and sacrificed to collect blood, liver, and kidney for analyses. Histopathological examinations showed that oral administrations with Silymarin and HWETT were effective in protecting the liver from CCl(4)-caused fatty change. Oral administration of HWETT at 125 mg/kg bw was more effective than was Silymarin at 200 mg/kg bw. On biochemical analyses, oral administrations with HWETT at medium and high doses were effective (p < 0.05) in lowering CCl(4)-caused increases of alanine aminotransferase and aspartate aminotransferase activities. It is of merit to demonstrate HWETT as a potent source of antioxidants and hepatoprotective agents.  相似文献   

11.
We studied the effects of a single oral administration of ferulic acid (FA) on the blood pressure (BP) and lipid profile in stroke-prone spontaneously hypertensive rats (SHRSP). Male 12-week-old SHRSP were administered FA (9.5 mg/kg of body weight) and distilled water as the control (C) (1 mL) via a gastric tube. The hypotensive effect of FA was observed at the lowest value after 2 h administration. A decrease in the angiotensin-1-converting enzyme (ACE) activity in the plasma corresponded well with the reduction of BP. Plasma total cholesterol and triglyceride levels were lower after 2 h administration. The mRNA expression of genes involved in lipid and drug metabolism was downregulated in the FA group. These results suggest that oral administration of FA appears beneficial in improving hypertension and hyperlipidemia.  相似文献   

12.
To clarify a postprandial glucose suppression effect of diacylated anthocyanin with alpha-glucosidase (AGH) inhibitory activity, a single oral administration study of it in male 8-week-old Sprague-Dawley rats was performed. The diacylated anthocyanin used in this study was peonidin 3-O-[2-O-(6-O-E-feruloyl-beta-D-glucopyranosyl)-6-O-E-caffeoyl-beta-D-glucopyranoside]-5-O-beta-D-glucopyranoside isolated from storage roots of the purple sweet potato (Ipomoea batatas cv. Ayamurasaki), which showed a potent maltase inhibitory activity with an IC(50) value of 200 microM preferable to sucrase inhibition. When the diacylated anthocyanin (100 mg/kg) was administered following maltose (2 g/kg), a maximal blood glucose level (BGL) at 30 min was significantly decreased by 16.5% (P < 0.01) compared to vehicle. A minimum 10 mg/kg dose of the anthocyanin was necessary for the suppression of glycemic rise, and the ED(20) (69 mg/kg) was estimated to be approximately 30-fold lower than that of the therapeutic drug acarbose (ED(20) = 2.2 mg/kg). A reduction of serum insulin secretion was also observed corresponding to the decrease in BGL. No significant change in BGL was observed when sucrose or glucose was ingested, suggesting that the anti-hyperglycemic effect of the anthocyanin was achieved by maltase inhibition, not by sucrase or glucose transport inhibition at the intestinal membrane.  相似文献   

13.
An optimal antihypertensive peptide (AHP), KVLPVP, was linked to form a six-copy of tandem dotetracontapeptide with the specific cleavage site (Arg-X) of clostripain. The gene of the dotetracontapeptide was synthesized and expressed in Escherichia coli BL21. After a 5 h induction with 1.2 mM isopropyl-beta-D-thiogalactopyranoside the recombinant AHP fused with glutathione-S-transferase tag reached the maximal production, 24.6% of total intracellular protein. Following digestion with clostripain and carboxypeptidase B, the product was separated with ultrafiltration and reversed-phase HPLC, and 170 mg of pure recombinant AHP was obtained from 1 L of E. coli culture. The IC50 of the recombinant AHP was 4.6 microM. The systolic blood pressure of spontaneously hypertensive rats could be decreased dramatically by the recombinant AHP in a dose-dependent manner after delivering 0.3 mg of AHP/kg of body weight (BW) or 0.6 mg of AHP/kg of BW orally. The strong antihypertensive effect was reached 4-24 h after oral administration of 0.3 mg of AHP/kg of BW, and the peak point was at the fourth hour (-21.4 +/- 7.2 mm of Hg). This study overcame traditional enzymatic digestion problems in preparing AHP and established a novel approach for industrial production of AHP.  相似文献   

14.
Toxicokinetic behavior, recovery, and metabolism studies of ACTP ester and its effect on cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goat after a single intravenous administration of 11.88 mg kg(-1) and consecutive oral administration of 79.22 mg kg(-1) for 7 days. ACTP ester achieved a maximum blood concentration of 42.64 +/- 4.26 microg mL(-1) at 0.08 h after intravenous administration followed by a sharp decline until 0.5 h, and the minimum blood concentration was recorded at 36 h (1.93 +/- 0.14 microg mL(-1)) postdosing. The kinetic behavior of ACTP ester followed a "two-compartment open model". Comparatively shorter alpha (0.81 +/- 0.02 h(-1)) and greater t1/2 (alpha) (0.86 +/- 0.03 h) indicated a slower rate of distribution of ACTP ester in goat. The t1/2(beta)()) (14.83 +/- 1.49 h) and V(d(area)) (0.91 +/- 0.19 L kg(-1)) suggested a longer elimination phase with general distribution in all compartments of the body. The higher T/B and K12/K21 values associated with a lower f(c) value suggested longer persistence in the tissue compartment at higher concentration. The higher Cl(R) compared to Cl(H) indicated the major amount was eliminated by the kidney. Maximum concentration of ACTP ester including its metabolites, triclopyr acid and trichloropyridinol, was excreted through urine at 48 h. The recovery of ACTP ester including metabolites after repeated nontoxic oral dose administration was 70.09%, of which recovery from feces was 4.45%, suggesting the major portion of administered ACTP ester was absorbed through the gastrointestinal tract of the goat. All of the tissues contained ACTP ester and its metabolites. ACTP ester did not alter the cytochrome P(450) content of the liver tissue following repeated nontoxic oral dose administration for 7 days.  相似文献   

15.
Toxicokinetic behavior and metabolism studies of metamitron and its effect on the cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goats after a single oral administration at 278 mg kg(-1) and consecutive oral administration of 30 mg kg(-1) for 7 days. Metamitron was detected in the blood sample at 0.08 h (12.0 +/- 0.87 microg mL(-1)), maximum at 4 h (84.3 +/- 8.60 microg mL(-1)) and minimum (14.6 +/- 1.67 microg mL(-1)) at 36 h blood sample after a single oral administration. The absorption rate constant was 0.69 +/- 0.09 h(-1). The Vd(area) (2.00 +/- 0.08 L kg(-1)) and t(1/2)beta (8.98 +/- 0.70 h) values suggested wide distribution and long persistence of the compound in the body. The values of T approximately B (0.80 +/- 0.04), F(c) (0.55 +/- 0.01), Cl(B) (0.15 +/- 0.00 L kg(-1) h(-1)), and K(21) (0.41 +/- 0.03 h(-1)) suggested that metamitron retained in the blood compared to that in the tissue. Maximum concentration of metamitron residue was found in the adrenal gland followed by bile on day 4 of single oral administration. The higher Cl(R) compared to Cl(H) value indicated the excretion of the major portion (34-40%) through urine compared to feces (20-26%). Maximum concentrations of metamitron and its metabolite, deaminometamitron, were excreted through urine and feces at 48 and 24 h samples, respectively. The recovery of metamitron including its metabolite in terms of parent compound varied from 69.3 to 80.1%, of which contribution of metabolite in terms of parent compound varied from 53.1 to 63.0%. Repeated oral administration of metamitron at 30 mg kg(-1) for 7 days caused induction of the cytochrome P(450) content of liver microsomal pellet of goat, suggesting oxidative deamination of metamitron.  相似文献   

16.
Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were studied following a single high-dose oral administration of 2.5 g kg(-1) and continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat. Napropamide was detected in blood at 15 min and the maximum quantity was recovered at 3 h after administration. The absorption rate constant (Ka) value was low indicating poor absorption from the gastrointestinal tract. High elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled with higher transfer of compound from tissue to central compartment (K(21)) suggest that napropamide persisted in the blood for a long time, i.e., after 72 h of oral administration. The recovery percentage of napropamide, including metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent compound through feces varied from 18.86 to 21.59%, indicating that a major portion of the orally administered napropamide was absorbed from the gastrointestinal tract of goat. Napropamide significantly increased the Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7--11.6%, respectively, during a 4--7 day period. The material balance of napropamide (including metabolites) following a single high-dose oral administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in the range of 75--80%.  相似文献   

17.
Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.  相似文献   

18.
In this study, we have identified novel antihypertensive peptides derived from egg-white proteins. The sequences YRGGLEPINF and ESIINF produced an acute blood-pressure-lowering effect in spontaneously hypertensive rats upon a single oral administration. Our results suggest that the antihypertensive action could be attributed to a vascular-relaxing mechanism that would occur in vivo independently of angiotensin I-converting enzyme (ACE) inhibition, because neither these peptides nor their main digestion fragments, except for the dipeptide YR, acted as ACE inhibitors in vitro. The vasodilator and antihypertensive activity of the sequences ESI and NF would explain the blood-pressure-lowering effect of ESIINF. With regard to YRGGLEPINF, in addition to NF, YR appeared as the main fragment responsible for its activity. The dipeptide YR, named kyotorphin and previously identified as an endogenous analgesic neuropeptide in the central nervous system, showed strong vasodilator and antihypertensive properties. The structure-activity features of the vasodilator peptides are discussed.  相似文献   

19.
It has been reported that soybean peptide fractions isolated from Korean fermented soybean paste exert angiotensin I converting enzyme (ACE) inhibitory activity in vitro. In this study, further purification and identification of the most active fraction inhibiting ACE activity were performed, and its antihypertensive activity in vivo was confirmed. Subsequently, a novel ACE inhibitory peptide was isolated by preparative HPLC. The amino acid sequence of the isolated peptide was identified as His-His-Leu (HHL) by Edman degradation. The IC(50) value of the HHL for ACE activity was 2.2 microg/mL in vitro. Moreover, the synthetic tripeptide HHL (spHHL) resulted in a significant decrease of ACE activity in the aorta and led to lowered systolic blood pressure (SBP) in spontaneously hypertensive (SH) rats compared to control. Triple injections of spHHL, 5 mg/kg of body weight/injection resulted in a significant decrease of SBP by 61 mmHg (p < 0.01) after the third injection. These results demonstrated that the ACE inhibitory peptide HHL derived from Korean fermented soybean paste exerted antihypertensive activity in vivo.  相似文献   

20.
The blood pressure lowering effect of a pea protein hydrolysate (PPH) that contained <3 kDa peptides, isolated by membrane ultrafiltration from the thermolysin digest of pea protein isolate (PPI), was examined using different rat models of hypertension as well as hypertensive human subjects. The PPH showed weak in vitro activities against renin and angiotensin converting enzyme (ACE) with inhibitory activities of 17 and 19%, respectively, at 1 mg/mL test concentration. Oral administration of the PPH to spontaneously hypertensive rats (SHR) at doses of 100 and 200 mg/kg body weight led to a lowering of hourly systolic blood pressure (SBP), with a maximum reduction of 19 mmHg at 4 h. In contrast, orally administered unhydrolyzed PPI had no blood pressure reducing effect in SHR, suggesting that thermolysin hydrolysis may have been responsible for releasing bioactive peptides from the native protein. Oral administration of the PPH to the Han:SPRD-cy rat (a model of chronic kidney disease) over an 8-week period led to 29 and 25 mmHg reductions in SBP and diastolic blood pressure, respectively. The PPH-fed rats had lower plasma levels of angiotensin II, the major vasopressor involved in development of hypertension, but there was no effect on plasma activity or renal mRNA levels of ACE. However, renal expression of renin mRNA levels was reduced by approximately 50% in the PPH-fed rats, suggesting that reduced renin may be responsible for the reduced levels of angiotensin II. In a 3-week randomized double blind placebo-controlled crossover human intervention trial (7 volunteers), significant (p<0.05) reductions (over placebo) in SBP of 5 and 6 mmHg were obtained in the second and third weeks, respectively, for the PPH group. Therefore, thermolysin derived bioactive peptides from PPH reduced blood pressure in hypertensive rats and human subjects, likely via effects on the renal angiotensin system.  相似文献   

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