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Angiotensin-converting enzyme inhibition by certain fruits: An in vitro study
Abstract
Angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a nonspecific dipeptidyl-carboxypeptidase that converts angiotensin I into a potent vasoconstricting, hypertensive angiotensin II. Inhibition of ACE results in an overall antihypertensive effect and several drugs are currently in use to inhibit the ACE activity such as captopril, enalapril etc. Purpose of the study was to determine the efficacy of Indian Gooseberry, Guava, Wood Apple and Star fruit for angiotensin converting enzyme (ACE) inhibitory activity using Hippuryl-L-histidyl-L-leucine (HHL) as a substrate. An in vitro study was carried out using sheep lung as an enzyme source and both dialyzed and undialyzed fruit extracts were used for testing their ability to reduce the ACE activity. The study revealed that both undialyzed and dialyzed extracts of all four fruits exhibited ACE inhibitory activity which could be due to the varied amounts of phytoconstituents present in the extracts (i. e., phenols, flavanoids, ascorbic acid and protein contents).
... The authors suggested that the inhibitory activity is owing to the presence of polyphenols and flavonoids linked with the mucilage. The foremost mechanism consists of inhibition of the synthesis of hepatic-3-hydroxy-3-methylglutaryl-Coenzyme-A which regulates the cholesterol synthesis 62 . Thus, the results are evidence of the potential of the natural product as an inexpensive and safe approach for cardioprotection/ hypertension. ...
The valorization of new polymer sources from underutilized plants as structuring, encapsulating, and texturizing agents for food and nutraceutical applications is gaining attention. This provides an opportunity where inexpensive plant-sourced biopolymers can play an impactful role, on both ecological and economic aspects performing equivalently effectual yet cost-effective substitutes to synthetic polymers. With this aim, we explored the use of mucilage from Althea rosea and reveal its physicochemical, in vitro antidiabetic and antihypertensive activity. Besides, structural, micrometric, crystallization, and anti-microbial properties was also seen. We determined the probable structure of the extracted mucilage by FTIR which confirmed the residues of saccharides as galactose and uronic acid with α and β configurations. It consists of 78.26% carbohydrates, 3.51% ashes, and 3.72% proteins. Here, we show that the mucilage offered protection to DNA against the oxidative damage caused by (-OH) radicals and the morphology of the mucilage particles displayed a fibrillary material settled in a net-like, tangled structure. Our results demonstrate that the reconstituted mucilage powder exhibited good water holding capacity (2.89 g water/g mucilage), solubility (27.33%), and oil holding capacity (1.79 g oil/g mucilage). Moreover, high emulsifying property (95.83%) and foaming capacity (17.04%) was noted. Our results indicate that A.rosea mucilage can potentially serve as economical and eco-friendly hydrocolloid substitute for the food and nutraceutical industry owing to its functional, hypo-lipidemic, anti-hyperglycemic, antioxidant, and anti-bacterial properties.
... Nowadays, scientists believe the effect of oxidative stress on blood pressure [28,29], and EO can be effective in the prevention or treatment of hypertension through its strong antioxidative properties [30]. More importantly, EO is a plant with the ACE (angiotensin-converting enzyme) inhibitor and diuretic activity which can explain its antihypertensive effect [31,32]. e strength of the present study was the triple-blind design and checking the medication adherence. ...
Introduction. Emblica officinalis (EO) has some cardiovascular effects, and there are some animal studies that show its antihypertensive effect. This study was conducted to determine the effect of combination of EO with standard therapy on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with uncontrolled hypertension. Materials and Methods. This was a randomized, triple-blind, placebo-controlled, 8-week study. Ninety-two patients with uncontrolled hypertension despite taking hypotensive drugs were randomly assigned into two groups to take EO (500 mg/TDS after meal) or placebo in combination with standard antihypertensive drugs. After 2, 4, 6, and 8 weeks of intervention, SBP and DBP and heart rate (HR) were measured. Data were analyzed by SPSS software using repeated measures ANOVA. Results. Eighty-one patients (41 in the drug group and 40 in the placebo group) completed the study for 8 weeks and were analyzed. The mean ± standard deviation of age was 53.64 ± 10.01 years. SBP decreased as 15.6 ± 8.23% in the EO group and 6.3 ± 7.49% in the placebo group (P < 0.001). DBP decreased as 12.3 ± 7.87% and 3.88 ± 7.98%, respectively (P < 0.001). Time effect was not significant, but the group effect was significant (F = 13.875, P=0.001 for systolic BP and F = 18.948, P < 0.001 for diastolic BP). No side effects were reported during the study. Conclusion. Eight-week combination therapy of EO with standard antihypertensive drugs significantly reduced the SBP and DBP more than placebo in patients with uncontrolled hypertension.
... All herbal extracts were estimated at the dose of 10mg/ml ( Narasimhacharya et al. (2010), who suggested that the activity was directly related to the quantity of flavonoids, polyphenols, phenolic acids, protein and ascorbic acid content of the herb extract. ACE inhibitory activity of tulsi reported as 21% in aqueous extract by Nymen et al. (1998), while for ashwagandha it was in range of 11-22%, depending on type of extract used. ...
Some herbal bioactives possess high antioxidant and angiotensin converting enzymes (ACE) inhibition activity, which affects blood pressure levels. Herbal bioactives promote health benefits via different molecular mechanisms and most of these mechanisms are yet to be fully elucidated. In the present study, health promoting potential of aqueous extracts of six herbs viz. Allium sativum L., Withania somnifera (L.) Dunal, Ocimum sanctum L., Hibiscus sabdriffa L., Ginkgo biloba L. and Emblica officinalis at different concentrations (50 to 10,000 μg/mL) were assessed through their antioxidant and ACE inhibitory potential. Results showed that the DPPH (2, 2-diphenyl-1-picrylhydrazyl) activity of the six different herbs ranged from 1.58 ± 0.63 to 11.39 ± 0.15 mM/mL trolox equivalent and was in the order of Emblica officinalis >Withania somnifera >Hibiscus sabdriffa >Ginkgo biloba >Ocimum sanctum =Allium sativum at 1000 μg/mL concentration. Emblica officinalis had IC50 value 180.35 ± 1.17 μg/mL. The corresponding observation for the herb with 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) was 167.19 ± 1.04 μg/mL. Ferric reducing antioxidant power (FRAP) values were significantly higher for Emblica officinalis than the other herbs, and varied from 1.78 ± 0.08 to 251.62 ± 6.31 mM/mL ascorbic acid equivalent at different concentrations (50 to 10000 μg/mL). Emblica officinalis had the strongest ACE inhibition potential (82.08 ± 5.18 %), followed by Withania somnifera, Hibiscus sabdriffa, Ginkgo biloba, Ocimum sanctum and Allium sativum. ACE inhibitory activity of herbs studied was lower (31.64 ± 5.05 %) than that of Captopril (0.002173 μg/mL), a standard medicine used for hypertension. The study compared and elucidated the antioxidant and ACE inhibitory potential of aqueous extracts of herbs at different concentrations. The study results may be useful in the selection of herbal bioactives for functional foods and aqueous nutraceutical formulations.
... In limited studies in human and murine models , Punica granatum L. (Lythraceae) or pomegranate juice has been shown to exert significant antihypertensive effects [29]. The efficacy of Indian gooseberry (Phyllanthus emblica L.) (Phyllanthaceae), guava (Psidium guajava), wood apple (Limonia acidissima L.) (Rutaceae) and star fruit (Averrhoa carambola L.) (Oxalidaceae) for angiotensin-converting enzyme (ACE) inhibitory activity using hippuryl-L-histidyl-Lleucine as a substrate was determined [30]. S. Das and B. De hypertension. ...
... In limited studies in human and murine models, Punica granatum L. (Lythraceae) or pomegranate juice has been shown to exert significant antihypertensive effects [29]. The efficacy of Indian gooseberry (Phyllanthus emblica L.) (Phyllanthaceae), guava (Psidium guajava), wood apple (Limonia acidissima L.) (Rutaceae) and star fruit (Averrhoa carambola L.) (Oxalidaceae) for angiotensin-converting enzyme (ACE) inhibitory activity using hippuryl-L-histidyl-Lleucine as a substrate was determined [30]. ...
Introduction. Angiotensin I-Converting Enzyme (ACE) is a key component in regulation of blood pressure by virtue of the rennin-angiotensin system. ACE converts the inactive decapeptide, angiotensin I, into the potent vasopressor octapeptide, angiotensin II, and inactivates bradykinin, which has a vasodilating action. So, inhibition of ACE has become a major target in control of hypertension. It is well known that the consumption of fruits could provide health benefits by lowering the risk of chronic diseases such as metabolic syndrome diseases including type 2 diabetes and cardiovascular disease. Our current study was focused on investigating the ACE inhibitory property of a few underutilized minor fruits of West Bengal using an in vitro assay. Materials and methods. The potential antihypertensive activity of underutilized indigenous edible fruits of West Bengal, India, was evaluated by their ability to inhibit Angiotensin-Converting Enzyme (ACE). The ACE inhibitory property was assayed using ACE from rabbit lung and hippuryl-histidyl-leucine as the substrate. Nineteen fruit species belonging to 15 families were investigated. The percentage ACE inhibitory activities of these fruits were studied at 20 μg fresh weight of fruit extract per mL. The total phenol content of all these fruits was determined following the standard Folin-Ciocalteu method. Total flavonoid content was also measured. Results. The aqueous fruit extracts of the red variety of Trapa bispinosa, Phoenix sylvestris, Cicca acida, Achras sapota and Averrhoa carambola presented more than 75% ACE inhibition. On the other hand, Punica granatum, Spondias pinnata, Trapa bispinosa (green) and Ziziphus mauritiana showed about 50% inhibition. Aegle marmelos, Annona squamosa, Annona reticulata, Feronia elephantum, Physalis peruviana and Syzygium jambos showed low activity (< 50% inhibition). Discussions. To date there has been no report on Angiotensin I-Converting Enzyme inhibitory activities of these underutilized minor fruits of West Bengal, India. During our study no correlation could be established between the % ACE inhibition and the total phenol or flavonoid content of these fruit extracts. So, it appears that non-phenolic components may also be responsible for ACE inhibitory activity. In our investigation we tried to establish the fact that the consumption of these underutilized minor fruits might have potential in managing cardiovascular diseases.
Fluorosis, caused by a chronic exposure to fluoride is a worldwide health problem known to affect various organ systems. The present study was aimed at investigating the effect(s) of extracts of seasonal fruits (Indian goose berry, star fruit, guava and wood apple) on angiotensin-converting enzyme (ACE) activity in the lung extracts exposed to different concentrations of fluoride. The lung extracts showed an increasing ACE activity with increasing concentrations of fluoride (2.5-10ppm) with highest ACE activity at 10ppm of fluoride. A reduction in the ACE activity was observed when the fluoride exposed (10ppm) lung extracts were incubated with fruit extracts; wood apple extract exerted a maximum ACE inhibitory activity (28.9%) followed by star fruit, guava and goose berry (20.1 %,19% and 15.5% respectively). A phytochemical analysis and the antioxidant potential of the fruits indicated that the fruits have a high antioxidant potential that correlated well with phytochemical content (phenols, flavonoids, saponins and ascorbic acid) of the fruits. It is suggested that the consumption of these seasonal fruits could be useful in regulating the ACE activity in fluoride endemic areas.
To study the quantitative changes in intramyocardial blood vessels in rats in whom nitric oxide synthesis was inhibited.
Four groups of 10 rats were studied: control (C25 and C40) and L-NAME (L25 and L40). The animals L25 and L40 received L-NAME in the dosage of 50mg/kg/day for 25 and 40 days, respectively. On days 26 and 41 the animals in groups 25 and 40 were sacrificed. Analysis of the myocardium was performed using light microscopy and stereology.
Arterial blood pressure and heart weight increased 74.5 and 57.8% after 25 days and 90.2 and 34.6% after 40 days, respectively. Comparing the L-NAME rats with the respective controls revealed that vessel volume density decreased 31.3% after 40 days, and the vessel length-density decreased 53.5% after 25 days and 25.7% after 40 days. The mean cross-sectional area of the vessels showed an important reduction of 154.6% after 25 days. The intramyocardial vessels decreased significantly in length-density in the L-NAME animals. The mean cross-sectional area of the vessels, which normally increases during heart growth between 25 and 40 days, showed a precocious increase by the 25th day in the L-NAME rats. This suggests an increase of the size of the heart, including blood vessels.
The inhibition of the NO synthesis provokes rarefaction in the intramyocardial vessels that progresses with the time of administration of L-NAME.
Ripened and unripened nendran, rasthali, poovan, robusta, bontha and safed velchi bananas were investigated for inhibition against angiotensin converting enzyme (ACE) using Hip-His-Leu as substrate. The inhibition of ACE by different ripened banana cultivars was much more than that of unripened banana cultivars. The ACE inhibitory activity of ripened and unripened poovan was heat stable and stable to extreme acidic pH and alkaline pH. The ACE inhibitory activity of ripened and unripened banana cultivars was reduced to 25% and 33% respectively on dialysis.
Aqueous extract of Emblica officinalis was found to be a potent inhibitor of lipid peroxide formation and scavenger of hydroxyl and superoxide radicals in vitro. The amount of the fresh pulp needed to inhibit 50% of lipid peroxidation was 1, 000μg/ml in the Fe2+/ascorbate system and 640μg/ml in the Fe3+/ADP-ascorbate one. The concentration needed for 50% inhibition of superoxide-scavenging activity was 107μg/ml in the method involving photoreduction of riboflavin and 232μg/ml in the xanthine-xanthine oxidase method, and that for hydroxyl radical scavenging (deoxyribose degradation method) was 3, 400μg/ml. An indigenous drug preparation containing Emblica officinalis, used in India as a health tonic, was also found to have a potent antioxidant activity. The antioxidants present in Emblica officinalis were aqueous soluble, but partially extractable with ether, and were heat stable.
The effect on total serum cholesterol and its lipoprotein fractions of supplementation of the diet with amla (Emblica officinalis, Gaertn., the Indian gooseberry) was studied in normal and hypercholesterolaemic men aged 35-55 years. The supplement was given for a period of 28 d in the raw form. Both normal and hypercholesterolaemic subjects showed a decrease in cholesterol levels. Two weeks after withdrawing the supplement, the total serum cholesterol levels of the hypercholesterolaemic subjects rose significantly almost to initial levels.
Five bradykinin-potentiating peptides (potentiators A, B, C, D, and E) were isolated from the venom of the Japanese poisonous snake, Agkistrodon halys blomhoffii, using gel filtrations on columns of Sephadex G-100, Sephadex G-10, and Sephadex G-25 and ion-exchange chromatography on a column of CM-Sephadex C-50. These five bradykininpotentiating peptides were characteristic in having a high proline content, 5 or 6 of the 11 amino acid residues being proline residues. The biological activities of these five peptides were measured using isolated guinea pig ileum and rat uterus. Of the five potentiators, B and C had the strongest bradykinin-potentiating activity on guinea pig ileum. On the other hand, only potentiator E showed high bradykininpotentiating activity on rat uterus, the other four peptides having very slight activity. These peptides did not cause contraction of smooth muscles in the absence of bradykinin. The amino acid sequences of two bradykinin-potentiating peptides, B and C, were determined to be as follows, and these were confirmed by chemical synthesis of the peptides: potentiator B: Pyr-Gly-Leu-Pro-Pro-Arg-Pro-Lys-Ile-Pro-Pro; potentiator C: Pyr-Gly-Leu-Pro-Pro-Gly-Pro-Pro-Ile-Pro-Pro.
Two dipeptides, phenylalanylarginine (Phe-Arg) and serylproline (Ser-Pro), are released sequentially from bradykinin by angiotensin converting enzyme purified from hog lungs; chloride increases the rate of release of both dipeptides. Using an automated ninhydrin reagent method, the kinetics of bradykinin hydrolysis were studied. The reaction proceeded in the absence of chloride; however, the addition of chloride increased the rate of hydrolysis by decreasing K(m) and increasing V(m). The K(m) values for bradykinin were 3.9 x 10 -6M in the absence of chloride and 0.85 x 10 -6M in the presence of 0.01M NaCl (optimal concentration). Both of these K(m) values were well below the value of 30 x 10 -6M determined for angiotensin I at its optimal chloride concentration of 0.1M. Hydrolysis of bradykinin had a pH optimum of seven and was inhibited by low concentrations (10 -6M) of ethylenediaminetetraacetic acid or the nonapeptide pyroglutamyl (Pyr)-Trp-Pro-Arg Pro-Gln-Ile-Pro-Pro. It is concluded that one enzyme, acting as a dipeptidyl carboxypeptidase, catalyzes the conversion of angiotensin I to angiotensin II and the hydrolysis of bradykinin.
To review current literature relating to the adverse effects of the angiotensin-converting enzyme (ACE) inhibitors.
Online drug information sources, including MEDLINE (1966-November 1994), Iowa Drug Information Service, and the Australian Medical Index (AMI), were used to identify relevant literature, including reviews.
Data were extracted from studies described in the English-language literature dealing with the adverse effects of ACE inhibitors. Comprehensive reviews and relevant case reports also were included.
Important adverse effects of ACE inhibitors include first-dose hypotension, renal dysfunction, hyperkalemia, and cough. Less common adverse effects include angioedema, hepatotoxicity. Skin rashes, and dysgeusia. ACE inhibitors also are associated with adverse fetal effects; thus, this class of drugs in contraindicated in pregnancy. Some adverse effects of ACE inhibitors are predictable on the basis of the fundamental pharmacology of this class of drugs. However, other effects are idiosyncratic in nature, although these reactions are generally much less common.
Attention to the principles of risk assessment, risk immunization, and patient monitoring are important when ACE inhibitor therapy is used for any indication. Provided these steps are taken. ACE inhibitors are generally a safe and effective class of drugs.
The potential antihypertensive activity of Brazilian plants was evaluated in vitro by its ability to inhibit the angiotensin-converting enzyme (ACE). Forty-four plants belonging to 30 families were investigated. Plants were selected based on their popular use as antihypertensive and/or diuretics. The following plants presented significant ACE inhibition rates: Calophyllum brasiliense, Combretum fruticosum, Leea rubra, Phoenix roebelinii and Terminalia catappa. (c) 2007 Elsevier B.V. All rights reserved.