Drug Captopril Research Articles

2,2‐Difluoroethylation of Heteroatom Nucleophiles via a Hypervalent Iodine Strategy

AbstractThe 2,2‐difluoroethyl group is an important lipophilic hydrogen bond donor in medicinal chemistry, but its incorporation into small molecules is often challenging. Herein, we demonstrate electrophilic 2,2‐difluoroethylation of thiol, amine and alcohol nucleophiles with a hypervalent iodine reagent, (2,2‐difluoro‐ethyl)(aryl)iodonium triflate, via a proposed ligand coupling mechanism. This transformation offers a complementary strategy to existing 2,2‐difluoroethylation methods and allows access to a wide range of 2,2‐difluoroethylated nucleophiles, including the drugs Captopril, Normorphine and Mefloquine.

2,2-Difluoroethylation of Heteroatom Nucleophiles via a Hypervalent Iodine Strategy.

The 2,2-difluoroethyl group is an important lipophilic hydrogen bond donor in medicinal chemistry, but its incorporation into small molecules is often challenging. Herein, we demonstrate electrophilic 2,2-difluoroethylation of thiol, amine and alcohol nucleophiles with a hypervalent iodine reagent, (2,2-difluoro-ethyl)(aryl)iodonium triflate, via a proposed ligand coupling mechanism. This transformation offers a complementary strategy to existing 2,2-difluoroethylation methods and allows access to a wide range of 2,2-difluoroethylated nucleophiles, including the drugs Captopril, Normorphine and Mefloquine.

Investigation of drug delivery capability of single-walled carbon and boron-nitride nanotubes, boron-nitride (B16N16), and C32 fullerenes as nanocarriers of captopril drug; DFT study

Density functional theory (DFT) calculations were performed on M062X/6-31G (d) and M062X/6-311G (d, p) surfaces to investigate the interaction of captopril molecules with single-walled carbon nanotubes (SWCNT) and C32 nanoclusters. In order to enhance adsorption, a doping method was employed, and structures of single-walled boron nitride nanotubes (SWBNNT) and boron nitride nanoclusters (B16N16) were selected for improved drug delivery purposes in this study. The adsorption energy of captopril on the nanostructures was calculated in both phases. In both phases, captopril adsorption energy on nanostructures was calculated. The negative values of adsorption energy showed that the interaction between captopril and nanostructures is exothermic. The adsorption energy values were higher in the gas phase compared to the aqueous phase, indicating a stronger interaction in the gas phase. The density of states (DOS) study was employed to evaluate the effect of molecular adsorption on the electronic properties of nanostructures. The results revealed that the B16N16 nanocluster approached the Fermi level more closely after drug adsorption compared to other nanostructures. Quantum Theory of Atoms in Molecules (QTAIM) calculations showed that there is a weak interaction between captopril and both nanostructures. Based on the adsorption energy values obtained from both methods, the interaction between captopril and SWCNT was found to be stronger than that between captopril and SWBNNT, whereas the interaction in the B16N16 nanocluster was found to be equal to that in C32-fullerene. Significant changes in ΔEg values were observed for Captopril@SWCNT and Captopril@B16N16-fullerene in each method, indicating the conductivity of these two structures increased more after captopril adsorption compared to other nanostructures. Therefore, SWBNNT and B16N16-fullerene can serve as captopril nanosensors.

Managing hypertension using brewing bioactive peptides as angiotensin-converting enzyme inhibitors: Impact on vascular tone through ex vivo assays

BackgroundPeptides derived from brewer’s spent grain (BSG) and yeast (BSY) are promising natural substitutes of synthetic drugs to manage hypertension as inhibitors of angiotensin-converting enzyme (ACE). However, their impact on the vascular function, so far, remains to be verified. Accordingly, we aimed to evaluate the effect of brewing peptides on the arterial vasocontractile response to angiotensin (Ang) I (through vascular ACE-inhibition) to estimate their antihypertensive potential. The impact of the oral route (gastrointestinal digestion, intestinal absorption, and liver metabolism) in brewing peptides was also investigated. MethodsIliac arteries from adult spontaneously hypertensive rats were studied with isometric tension recording. After ensuring the function integrity of the arteries, concentration-response curves to addition of Ang I (10−9-10−6 M) were performed after 30 min incubation with MIX (50:50 mixture of BSG:BSY) or BSG (0.86 mg/mL), or captopril (an ACE-inhibitory drug) or Krebs solution. ResultsMIX peptides (without simulated oral administration) enhanced Ang I-induced vasoconstriction, but lacked vascular effects after simulated oral administration. By contrast, BSG peptides (without simulated oral administration) did not exhibit vascular effects, whereas they promoted a marked decrease in vasocontraction evoked by the generated Ang II after simulation of the oral route, implying their capability to inhibit ACE. Additionally, to elucidate this inhibitory mechanism, Michaelis-Menten and Lineweaver-Burk plots indicated a mixed inhibition type. ConclusionWith simulation of the oral route, BSG peptides were able to inhibit vascular ACE with a similar efficacy as the antihypertensive drug captopril, suggesting the potential to mitigate the burden of hypertension.

Redirecting pantoprazole as a metallo-beta-lactamase inhibitor in carbapenem-resistant Klebsiella pneumoniae.

The development of resistance to carbapenems in Klebsiella pneumoniae due to the production of metallo-β-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum β-lactamases (ESBLs) producing K. pneumoniae. Restoring the activity of carbapenems by the inhibition of metallo-β-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant K. pneumoniae isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-β-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-β-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-β-lactamase genes bla NDM and bla VIM. A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-β-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-β-lactamases producing K. pneumoniae.

Antihypertensive activity of spray-dried nanoemulsion containing Asiatic acid-Palm oil in high salt diet-fed rats

Asiatic acid (AA) is a compound isolated from Centella asiatica, which possesses significant antihypertensive activity. Several studies have shown that its hypertensive activity can be attributed to various mechanisms, such as Angiotensin-Converting-Enzyme (ACE) inhibition in the renin-angiotensin-aldosterone system (RAAS) pathway. Meanwhile, palm oil (PO) is an antioxidant, which has proven to have synergistic effects with the compound by preventing arterial thrombosis and atherosclerosis. Despite these synergistic effects, AA dosage in antihypertensive therapy has been reported to be relatively high compared to the common synthetic drug captopril. Therefore, this study aimed to produce spray-dried powder of nanoemulsion to enhance the solubility of AA, decrease the possibility of oxidation, and increase its activity. Redispersed AA nanoparticles were also successfully obtained during the synthesis process. Several evaluations were carried out, including particle size, particle distribution, zeta potential, cell viability, and antihypertensive activity in rats to ensure the improvement of physicochemical characteristics and activity as antihypertensive agent. The results showed that AA succeeded in forming nanoemulsion with excipients. In addition, it was encapsulated in a maltodextrin carrier, exhibiting good physicochemical characteristics and safety to the Caco-2 cells. The redispersion of the spray-dried powder yielded nanoparticles with a size of 217.4 ± 10.196 nm. The spray-dried nanoemulsion of AA also had faster effect than non-formulated AA (raw powder) in lowering the blood pressure of hypertensive Sprague-Dawley (SD) rats. Graphical abstract:

Improved Cardiovascular Effects of a Novel Pomegranate Byproduct Extract Obtained through Hydrodynamic Cavitation.

The healthy properties of pomegranate fruit, a highly consumed food, have been known for a long time. However, the pomegranate supply chain is still rather inefficient, with the non-edible fraction, whose weight is roughly half the total and is endowed with plenty of valuable bioactive compounds, either disposed of or underutilized. A novel extract obtained from non-edible byproducts (called PPE), using hydrodynamic cavitation, a green, efficient, and scalable technique, was investigated for its cardiovascular effects in vivo. PPE showed efficacy in an acute phenylephrine (PE)-induced hypertensive rat model, similar to the extract of whole fruit (PFE) obtained using the same extractive technique, along with good intestinal bioaccessibility after oral administration. Finally, when chronically administered for 6 weeks to spontaneously hypertensive rats, PPE was shown to significantly contain the increase in systolic blood pressure, comparable to the reference drug Captopril, and at a dose remarkably lower than the reported effective dose of ellagic acid. The extract from the non-edible fraction of the pomegranate fruit also showed good anti-inflammation and anti-fibrotic effects. The findings of this study, along with the extraction technique, could contribute to enhancing the value of the pomegranate supply chain, relieve the related environmental burden, and potentially improve public health.

Physicochemical investigation of encapsulation of antihypertensive drug captopril in mixed micellar system to enhance its delivery

This research work provides insight into the solubilization of a non-ionic drug captopril (CAP) in the micellar media of cationic surfactant cetyltrimethylammonium bromide (CTAB) and mixed micellar media of two nonionic surfactants Tween-80 and Triton X-100. CAP−surfactant interactions were analyzed by simple and differential absorption spectroscopy as well as by conductometry and the efficiency of the selected micellar system was assessed by calculating the values of partition coefficient (Kx), the free energy of partition (∆GP), binding constant (Kb) and the free energy of binding (∆Gb). Results from differential spectroscopy depicted a noteworthy increase in the solubilization of CAP with the addition of nonionic surfactants (Tween-80 and TX-100) in the micellar solution of CTAB. Furthermore, conductometric response of micellar media has been used to calculate the degree of dissociation (β), the free energy of micellization (∆Gm) thermodynamic parameters of micellization.

The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril-hypersensitive mutants. We identified a missense mutation that causes a partial loss of function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNA interference promoted dauer larvae formation, suggesting that acn-1 is a daf gene. Captopril-mediated lifespan extension was abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 influence lifespan by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.

DETERMINATION OF THE ANTIHYPERTENSIVE DRUGS CAPTOPRIL, ATENOLOL, AND METOPROLOL IN DOSAGE FORMS

Three antihypertensive drugs Captopril (CPL), Atenolol (ATL), and Metoprolol (MTL) have been estimated sensitively and selectively by a single spectrophotometric method using neutral red dye NLR. The method is based on oxidation of the drugs by known excess of N-bromosuccinamide (NBS) in the first reaction step followed by the oxidation of NLR dye with the exceed ed amount of NBS, as the concentration of the drug compounds increase, the color of the dye increase, the dye exhibits absorbance peak at 523 nm. The linearity range was from 1 to 10 µg/ml for the three drugs, the molar absorptivity values were 2.1164 × 105, 1.9202× 104, and 57.934× 104 l.mol-1.cm-1 for CPL, ATL, and MTL respectively, the sensitivity index of Sand’ll were 0.0102, 0.0138, and 0.01182 µg/cm2 for CPL, ATL, and MTL respectively. LOD values for the three drugs ranged from 0.00405 to 0.00547 and LOQ values were ranged from 0.0135 to 0.0182 respectively, the method exhibits good applicability to the dosage forms and high confidence as compared with standard method and standard addition method.

HUBUNGAN DRUG RELATED PROBLEMS (DRPs) KATEGORI DOSIS OBAT AMLODIPIN DAN KAPTOPRIL TERHADAP KONDISI TEKANAN DARAH PADA PASIEN HIPERTENSI

The incidence of drug-related problems (DRPs) in the dose category on the use of antihypertensive drugs has been associated with the failure of the patient's optimal blood pressure target. The study aims to analyze the relationship between drug-related problems (DRPs) on administering amlodipine and captopril drugs to the blood pressure conditions of elderly hypertensive patients in Puskesmas. This research is observational research with a cross-sectional design of analytical nature—purposive sampling techniques. The total number of samples meeting the inclusion and exclusion criteria was 435 patients. Analysis of DRPs dose category relationship data on administration of amlodipine and captopril against blood pressure conditions using a chi-square test. The results of the study showed that the characteristics of patients visited tended to be aged 65-69 years (53.33%), female (68,51%), stage II hypertensive (62.1%), amlodipine (80.92%). The incidence of the DRP dose category in stage II hypertensive (7.6%). Statistically known DRPs of amlodipine and captopril dosing categories showed different significance in each patient's condition of prehypertension (p=0.260), hypertension stage I (p = <0,001), hypertensive stage II (p<0,001). This study concludes, there is a relationship between the incidence of DRPs in the dose category in patients with stage I and stage II hypertension.

Computational molecular modelling of proline derivatives as ACE inhibitors

Objective: The study aims to design Proline derivatives having anti-hypertensive activity by computational molecular modelling. Methods: Various methodology used in the study include lead identification, selecting derivatives, molecular modelling, target identification, docking and visualizing the output. The ligands that show good binding scores are selected and Captopril was selected as standard drug. Results: In this study, we designed various derivatives of acylated proline into a ligand having ACE Inhibitor activity. All the twenty designed derivatives showed more binding affinity towards the receptor compared to the standard drug Captopril. Conclusions: The work concluded that the designed twenty ligands are promising ACE Inhibitors which provides anti-hypertensive activity.

GREEN PROCEDURE INDEX ASSESSMENT OF THE NOVEL STABILITY-INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF CAPTOPRIL FROM PHARMACEUTICAL DOSAGE FORM

Objective: In this study, it was aimed to develop a novel reverse-phase liquid chromatography method for the ultra-sensitive determination of the antihypertensive drug captopril, using paracetamol, which is the common pain killer, as the internal standard. Optimization of all experimental conditions including composition of mobile phase, flow rate, and column temperature was carried out step by step, and the method validity of the developed method was examined according to international validation guidelines. Calibration range, linearity, the limit of determination, the limit of quantification, robustness, accuracy from commercial tablet samples, and method stability were examined in detail. In addition, the greenness profile for the developed method was assessed with the Green Analytical Procedure Index and Analytical Greenness Calculator techniques, which are frequently used in the literature. Material and Method: The chromatographic method was conducted with an XBridge C18 column (25 cm x 4.6 mm ID; 5 µm) packed with fully porous silica materials. All analyses were performed isocratically with a mobile phase containing acetonitrile:5 mM, pH 7.0 ammonium acetate solution (50:50, v/v) at a flow rate of 1.5 ml min-1. The injection volume was 5 μl, and the column was kept at 25°C in a column oven. The column eluate was monitored at 220 nm. Under optimized conditions, retention times of captopril, and paracetamol were approximately 1.59, and 2.0 min, respectively. Result and Discussion: This study described a fully validated, simple, sensitive, accurate, linear, precise, and reproducible reversed-phase liquid chromatography method for the determination of captopril in tablet samples. Under optimal experimental conditions, the linear range was found in the range of 0.5-200 µg ml-1 and the correlation coefficient was greater than 0.99. Method precision was acceptable, with coefficients of variation between 0.05% and 0.61%. In addition, as a result of the recovery studies carried out on the tablet samples, the accuracy was found to be within satisfactory limits between 99.45% and 102.55%. Moreover, the greenness profile of the developed method also showed that the method is environmentally friendly.

Dissolution Profile Study and Uniformity of Dosage Units Test for Various Manufacturers of "Captopril" Drugs from the Russian Market

Introduction. As part of a comparative assessment of drugs quality available on the Russian market a dissolution profile studies and uniformity of dosage units test was conducted for various manufacturers of "Captopril" drugs. Drug release studies in three dissolution media (0.1 M hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8) with sampling at 0, 5, 10, 15, 20, 30 min and analysis using UV/Vis spectrophotometer at 212 nm were conducted. Dissolution kinetics was compared based on calculation of the similarity factor f2 and the values of relative standard deviations. Uniformity of dosage units test of scored tablets were evaluated based on HPLC-UV analysis and AV factor calculation.Aim. The purpose of this study was a comparative evaluation of "Captopril" drugs from various manufacturers on the Russian market based on dissolution profile studies and uniformity of dosage units test of scored tablets in order to assess the quality of the tablets.Materials and methods. To prove the dissolution profile studies DT 827/1000 tester (ERWEKA GmbH, Germany) was applied. Each drug in three dissolution media in 12 replicates for each dissolution medium was analyzed. The selected samples were analyzed on a UV 1800 UV spectrophotometer (Shimadzu, Japan) at a of 212 nm. In uniformity of dosage units test of scored tablets each tablet was divided according to the applied mark. Sample preparation was carried out in accordance with a validated method and samples were analyzed by HPLC-UV using Agilent 1260 (Agilent Technologies, США).Results and discussion. Based on the results of dissolution profile studies and calculations of the similarity factors and values of the relative standard deviation it can be concluded that the dissolution kinetics for drug no. 4, drug no. 5, drug no. 6 are not equivalent in comparison with the reference drug. During the uniformity of dosage units test of scored tablets, no deviations were found in accordance with the requirements of the RF Pharmacopoeia OFS.1.4.2.0008.18 "Uniformity of dosing" and the EAEU Pharmacopoeia OFS.2.1.9.14 "Uniformity of Dosed Units".Conclusion. The conducted dissolution profile studies and uniformity of dosage for scored tablets of Captopril drugs show the example of possibility to identify potential problems with drugs quality presented on the Russian market and as a result improve and maintain quality assurance of drugs for the national healthcare system.

Controlled release study for captopril by using polymer carboxymethyl cellulose

The present study was done to prepare tablet for captopril (CAP) which used in the treatment of hypertension and heart failure. CAP is mainly absorbed from the proximal intestine and to a lesser extent from the stomach. The tablets of CAP were prepared by using the polymer carboxymethyl cellulose (CMC) a captopril drug release system. The buffer solutions were use at (pH=12,7.4,8.5) as a media to release the drug similitude of the acidity index in stomach, in testiness, and blood plasma respective. It was accounted the concentrations of the drug that release in the above–mentioned solutions at the different temperature (25,30,37,40,45,) C°. The study was extended to the effect of the temperature and the acidity function on releasing the drug. The drug release from the polymers increased with the temperature and the degree of the solution acidity. It was also studied the value of stability constant that increased with the temperature.

Identification of Bioactive Peptides from a Laminaria digitata Protein Hydrolysate Using In Silico and In Vitro Methods to Identify Angiotensin-1-Converting Enzyme (ACE-1) Inhibitory Peptides.

Bioactive peptides range in size from 2-30 amino acids and may be derived from any protein-containing biomass using hydrolysis, fermentation or high-pressure processing. Pro-peptides or cryptides result in shorter peptide sequences following digestion and may have enhanced bioactivity. Previously, we identified a protein hydrolysate generated from Laminaria digitata that inhibited ACE-1 in vitro and had an ACE-1 IC50 value of 590 µg/mL compared to an ACE-1 IC50 value of 500 µg/mL (~2.3 µM) observed for the anti-hypertensive drug Captopril©. A number of peptide sequences (130 in total) were identified using mass spectrometry from a 3 kDa permeate of this hydrolysate. Predicted bioactivities for these peptides were determined using an in silico strategy previously published by this group utilizing available databases including Expasy peptide cutter, BIOPEP and Peptide Ranker. Peptide sequences YIGNNPAKGGLF and IGNNPAKGGLF had Peptide Ranker scores of 0.81 and 0.80, respectively, and were chemically synthesized. Synthesized peptides were evaluated for ACE-1 inhibitory activity in vitro and were found to inhibit ACE-1 by 80 ± 8% and 91 ± 16%, respectively. The observed ACE-1 IC50 values for IGNNPAKGGLF and YIGNNPAKGGLF were determined as 174.4 µg/mL and 133.1 µg/mL. Both peptides produced sequences following simulated digestion with the potential to inhibit Dipeptidyl peptidase IV (DPP-IV).

PROFIL PENGGUNAAN OBAT PADA PASIEN STROKE ISKEMIK PADA PASIEN DI POLI NEUROLOGI

Background:Stroke is one of the main causes of mortality. WHO defines stroke as a spatial neurological disorder with sudden onset, lasting more than 24 hours without any cause and causing serious long-term disability in Indonesia and the United States. Objectives; This study aimed to determine the profile of ischemic stroke drugs usage in patients of Aceh Tamiang Hospital and the use of types of drugs given to ischemic stroke patients.Method; This study was non-experimental prospectively by using a questionnaire on ischemic stroke patients in October 2020. The data was processed using Microsoft Excel.Results; The results of 26 respondents and the drugs issued in October for the neurology clinic at Aceh Tamiang Hospital obtained antiplatelet drugs, namely aspirin 80mg/tab with a total of 238 drugs (38.3%) and pletaal 50mg/caplet with a total of 42 drugs (6.7%). The neuroprotectant group was pirassetam 80mg/tab with 140 drugs (22.5%). The antihyperlipidemic group of the drug simvastatin 5 mg/tab totaled 21 drugs (3.4%). The antihypertensive drug class was amlodipine 10mg/tab total 28 drugs (4.5%), amlodipine 5mg/tab total 56 drugs (8.9%), captopril drug type 25 mg/tab total 63 drugs (10.2%), the type of drug furosemide dose 40mg/tab the amount of 35 drugs (5.6%).Conclusion; Drugs that were widely used in patients with ischemic stroke are the antiplatelet group, namely aspirin 80mg/tab obtained 238 tablets (38.3%), the neuroprotectant class of the drug piracetam 800mg/cap were 140 caplets (22.5%), the antihypertensive group amlodipine 5mg/tab were 56 tablets (8.9%), the antihyperlipidemic group of the simvastatin 5mg/tab were 21 tablets (3.4%).

Developing Metal Complexes for Captopril Quantification in Tablets Using Potentiometric and Conductometric Methods.

Potentiometric and conductometric methods were successfully applied to elucidate the interaction of 10 ions, viz., Cr3+, Fe3+, La2+, Th4+, Co2+, Mn2+, Pd2+, Sr2+, Ti2+, and Zr2+, with the antihypertensive drug captopril (CAP) and its role to determine CAP in pure powder and tablet forms. The ionization constant of CAP and the generated complexes' stability constants (log K) were evaluated using potentiometric and conductometric methods at 25 ± 0.1 °C and 0.05 M ionic strength (I) of NaNO3 aqueous solution, and CAP was then determined in pure powder and tablet forms. Complexes having metal:ligand ratios of 1:1, 1:2, and/or 1:3 were produced, regardless of the type of the ligand or metal ions. Both the suggested potentiometric and conductometric procedures were utilized to confirm the stoichiometry of the M-CAP binary complexes formed. These two different techniques were utilized successfully to determine CAP in pure powder and tablet forms. Using the standard addition method (SAM) based on the Gran plot, CAP was satisfactorily determined throughout the concentration range of 0.83-13.04 mg/mL (SD = 0.20, R = 0.9986 (n = 5)), with a detection limit of 0.64 mg/mL (SD = 0.20, R = 0.9986 (n = 5)). In the presence of common tablet excipients, no interferences were observed. The percentage of CAP recovered from various dosage formulations (tablets) varied from 95.88 to 99.92%.

Antihypertensive potential of Brassica rapa leaves: An in vitro and in silico approach.

Aim: Plants contain many essential constituents and their optimization can result in the discovery of new medicines. One such plant is Brassica rapa that is commonly used as a vegetable to fulfill daily food requirements worldwide. This study intends to screen the phytochemicals, antihypertensive potential, GC-MS, and in silico analysis of the leaves of Brassica rapa. Methods: Powdered leaves were subjected to proximate analysis followed by estimation of primary metabolites. Extracts were obtained by hot and cold extraction and investigated for secondary metabolites. All crude extracts were screened for their antihypertensive potential using an angiotensin-converting enzyme (ACE) inhibition assay. GC-MS analysis was carried out to standardize the extract, and an antihypertensive metabolite was confirmed using an in silico approach. Results: Physicochemical evaluation resulted in moisture content (9.10% ± 0.1), total ash value (18.10% ± 0.6), and extractive values (water 9.46% ± 0.5 and alcohol soluble 4.99% ± 0.1), while phytochemical investigation revealed primary metabolites (total proteins 11.90 mg/g ± 0.9; total fats 3.48 mg/g ± 0.5; and total carbohydrates 57.45 mg/g ± 1.2). Methanol extract showed the highest number of secondary metabolites including polyphenols 93.63 mg/g ± 0.6; flavonoids 259.13 mg/g ± 0.6; and polysaccharides 56.63 mg/g ± 1.4, while water extract (70 mg/g ± 2) was rich in glycosaponins. Methanol extract showed the highest antihypertensive potential by inhibiting ACE (79.39%) amongst all extracts, compared to the standard drug captopril, which inhibited 85.81%. Standardization of methanol extract via GC-MS analysis revealed potent phytoconstituents, and a molecular docking study confirmed that oleic acid is the main antihypertensive metabolite. Conclusion: We conclude that leaves of Brassica rapa can successfully lower hypertension by inhibiting ACE, however; in vivo investigations are required to confirm this antihypertensive activity.

Application of the ATC/DDD Method to Evaluate Captopril and Nifedipine Usage in Bluluk-Lamongan Regency Healthcare Service

Hypertension occurs when the systolic blood pressure is more than 140 mmHg and the diastolic is more than 90 mmHg. Hypertension might cause damage to the body’s organs directly or indirectly. This study aimed to analyze the use of the drugs Captopril and Nifedipin at the Bluluk Health Center, Bluluk District, Lamongan using the ATC/DDD method. This was an observational study with a retrospective descriptive design. Data collection was carried out using quantitative methods, more specifically the ATC/DDD method. The results of DDD/1000 inhabitants/day of the drug Nifedipine 10 mg in 2020 were highest in January, namely 0.98 mg, and the lowest was 0.17 mg in October with an average of 0.46 mg. For DDD/1000 inhabitants/day, the drug Captopril 12.5 mg in 2020, the highest in January was 3.6 mg and the lowest in May was 0.4 mg with an average of 1.6 mg. For DDD/1000 inhabitants/day, the drug Captopril 25 mg in 2020 was the highest in August at 7.6 mg and the lowest in April was 1.2 mg with an average of 3.7 mg. The DDD value of Nifedipine 10 mg was less than the World Health Organization value of DDD Nifedipine, which is 30 mg. The DDD value of Captopril (12.5 mg and 25 mg) was also less than the World Health Organization DDD of 50 mg, so it can be concluded that the use of Nifedipine 10 mg and Captopril (12.5 mg and 25 mg) is still controlled.
 Keywords: Captopril, Nifedipine, ATC/DDD, hypertension, healthcare service