Diuretic Activity Research Articles

QSAR analysis and molecular docking study of pyrrolo- and pyridoquinolinecarboxamides with diuretic activity

The aim. The aim of the study was to reveal QSAR and ascertain the possible mechanism of action via docking study in the row of tricyclic quinoline derivatives with diuretic activity.
 Materials and methods. Pyrrolo- and pyridoquinolinecarboxamides with proven diuretic activity were involved in the study. Molecular descriptors were calculated using HyperChem and GRAGON software, and QSAR models were built using BuildQSAR software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used.
 Results. Multivariate linear QSAR models were built on two datasets of quinolinecarboxamides: Vol = a∙X1 + b∙X2 + c∙X3 + d, where Vol – volume of the daily produced urine in rats, Xi – molecular descriptor. QSAR analysis showed that the diuretic activity is determined by the geometric and spatial structure of molecules, logP, the energy values, RDF- and 3D-MoRSE-descriptors. Based upon internal and external validation of the models, the most informative two-parameter linear QSAR model 3а was proposed. Docking data showed the high affinity of two lead compounds to the carbonic anhydrase II.
 Conclusions. QSAR analysis of tricyclic quinoline derivatives revealed that the diuretic activity increases with the increase of value of logP, refractivity, and dipole moment and with the decrease of volume, surface area, and polarization of the molecules. Increase of values of such energy descriptors as bonds energy, core-core interaction, and energy of the highest occupied molecular orbital results in higher diuresis; decrease in hydration energy leads to higher diuretic activity. Based upon molecular docking calculation, the mechanism of diuretic action is proposed to be carbonic anhydrase inhibition.
 QSAR models and docking data are useful for in-depth study of diuretic activity of tricyclic quinolines and could be a theoretical basis for de novo-design of new diuretics

ИЗУЧЕНИЕ ДИУРЕТИЧЕСКОЙ И ПРОТИВОВОСПАЛИТЕЛЬНОЙ АКТИВНОСТИ НАСТОЯ И ЭКСТРАКТА СУХОГО ЛИСТЬЕВ ЗЕМЛЯНИКИ САДОВОЙ

The search for new sources of medicinal plant raw materials for the production of drugs is one of the urgent tasks of modern pharmacy. The expansion of the range of medicinal plant raw materials is possible, first of all, due to the types systematically close to the official ones. In medical practice, wild strawberry leaves are used. Wild strawberry leaves are used in medicine as a diuretic, anti-inflammatory, antispasmodic, choleretic, hypoglycemic, antipyretic, hypolipidemic, antimicrobial and appetite-enhancing agent. Earlier studies of strawberry leaves have shown that they have a rich chemical composition and are widely cultivated in Russia, being an affordable source for mass procurement of raw materials, and are not used in scientific medicine. At the same time, in folk medicine, strawberry garden leaves are used similarly, and sometimes instead of wild strawberries. The proximity of the composition of biologically active substances of wild strawberries and garden strawberries. To expand the modern nomenclature of medicines, studies on the comparative study of the toxicity and pharmacological activity of infusions and extraction forms from medicinal plant raw materials of strawberry leaves are relevant. In this regard, the study of the toxicity, diuretic and anti-inflammatory activity of the infusion of garden strawberry leaves and the extract of dry strawberry leaves is of practical interest for the formation of a scientific justification for their use in medical practice.

In vivo antidiabetic potential of standardized Gymnocarpos decandrus Forssk. Extract.

Gymnocarpos decandrus (Caryophyllaceae) is a well-known wild plant used as a food for grazing animals. Recently it showed potent antidiabetic potential beside its established anti-inflammatory, analgesic and diuretic activities. G. decandrus antidiabetic potential was reported through in-vitro models and resulted in promising α-amylase, α-glucosidase and antiviral Coxsackie B4 inhibitory activities; however no in-vivo studies were conducted. This study aims to examine Gymnocarpos decandrus ethanol extract (GDEE) safety and to evaluate its in vivo antidiabetic potential. Adult albino rats were injected intraperitoneally with alloxan to induce diabetes mellitus and the glucose level was measured after two and four weeks against metformin as a standard drug. Additionally, GDEE characterization and standardization were carried out. GDEE LD50 was up to 5.8mg/kg and exhibited significant antidiabetic activity 77.17% comparable to the standard drug metformin. Its total phenolics, and flavonoids amounted 127.2 ± 0.23 and 85.5 ± 0.21mg/g respectively. Vitexin was used as a marker compound for GDEE (140.70mg/100 gm). This study represents the sole in vivo scientific validation of G. decandrus recently documented in vitro antidiabetic potential.

Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides

Quinoxaline is a privileged pharmacophore that has broad-spectrum applications in the fields of medicine, pharmacology and pharmaceutics. Similarly, the sulfonamide moiety is of considerable interest in medicinal chemistry, as it exhibits a wide range of pharmacological activities. Therefore, the therapeutic potential and biomedical applications of quinoxalines have been enhanced by incorporation of the sulfonamide group into their chemical framework. The present review surveyed the literature on the preparation, biological activities and structure-activity relationship (SAR) of quinoxaline sulfonamide derivatives due to their broad range of biomedical activities, such as diuretic, antibacterial, antifungal, neuropharmacological, antileishmanial, anti-inflammatory, anti-tumor and anticancer action. The current biological diagnostic findings in this literature review suggest that quinoxaline-linked sulfonamide hybrids are capable of being established as lead compounds; modifications on quinoxaline sulfonamide derivatives may give rise to advanced therapeutic agents against a wide variety of diseases.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Aegle marmelos (L.) (Bael): A Systematic Review

Aegle marmelos is a plant in the Rutaceae family that is one of the most significant in the medicinal field due to its properties. Bilwa is used to treat a variety of medical problems. Since the time of the dinosaurs, this plant has existed. The plant contains a variety of pharmacological qualities, including wound healing, antipyretic potential, antidiarrheal activity, Diuretic activity, Ulcer healing, and more. Antithyroid activity, Immunomodulatory activity, Antifungal activity, Antimicrobial activity, Antioxidant activity, Radioprotective effect, Contractile activity, Antiarthritis activity, Analgesic activity, Cytoprotective effectuate-constipating effect. Alkaloids, Terpenoids, Vitamins, Coumarins, Tannins, Carbohydrates, Flavonoids, Fatty Acids, Essential Oils, and other miscellaneous chemicals are among the identified constituents. This study summarises information about the A. marmelos' morphology, distribution, phytochemistry, traditional uses, and biological activity.
 Keywords: Aegle marmelos, Phytochemistry, morphology, pharmacological properties.

Analysis of the relationship between the predicted biological activity and the chemical structure of S-derivatives of 5-(5-bromofuran-2-yl)-4R-1,2,4-triazole-3-thiols

1,2,4-Triazole derivatives are actively used as components in the development of new drugs, plant protection products, polymeric materials, anti-corrosion agents and etc. Chemical modeling of substituted 1,2,4-triazoles due to the introduction of different pharmacophores into the structure is very popular among scientists in various fields. Today it is known that some S-derivatives of 5-(5-bromofuran-2-yl)-4R-1,2,4-triazole-3-thiols have antimicrobial activity. The aim of the work is to analyze the relationships between the predicted biological activity and the chemical structure of S-derivatives of 5-(5-bromofuran-2-yl) -4R-1,2,4-triazole-3-thiols. Materials and methods. Virtual screening of compounds was performed using the computer program PASS (Prediction of activity spectra for substances). The results of the forecast were issued in the form of a list of names of probable types of activity with estimates of the probabilities of presence (Pa) and absence of each activity (Pi), which had values from 0 to 1. Results. Analyzing the prediction of biological activity on protein targets from the group of enzymes, we can said that derivatives of 5-(5-bromofuran-2-yl)-4R-1,2,4-triazole-3-thiols were active in the group of oxyreductases (Glutathione reductase, mitochondrial; Cyclooxygenase-2; Hypoxia-inducible factor prolyl hydroxylase 2), which catalyzed oxidation reactions, the transfer of electrons from one molecule (reducer, electron donor) to another (oxidant, electron acceptor). These compounds can demonstrate antioxidant, antihypoxic activity. Conclusions. The conducted forecast of biological activity revealed that derivatives of 5-(5-bromofuran-2-yl)-4R-1,2,4-triazole-3-thiols are the most active and there is a probability to show antitumor, antiviral, antibacterial, diuretic, actoprotective, and antioxidant activity.

Heliotropium indicum L.: From Farm to a Source of Bioactive Compounds with Therapeutic Activity

This study aimed to summarize the available data on the ethnomedicinal and phytopharmacological activities of Heliotropium indicum L. based on database reports. For this purpose, an up-to-date literature search was carried out in the Google Scholar, Scopus, Springer Link, Web of Science, ScienceDirect, ResearchGate, PubMed, Chem Spider, Elsevier, BioMed Central, and patent offices (e.g., USPTO, CIPO, NPI, Google patents, and Espacenet) for the published materials. The findings suggest that the plant contains many important phytochemicals, including pyrrolizidine alkaloids, indicine, echinitine, supinine, heleurine, heliotrine, lasiocarpine, acetyl indicine, indicinine, indicine N-oxide, cynoglossine, europine N-oxide, heleurine N-oxide, heliotridine N-oxide, heliotrine N-oxide, heliotrine, volatile oils, triterpenes, amines, and sterols. Scientific reports revealed that the herb showed antioxidant, analgesic, antimicrobial, anticancer, antituberculosis, antiplasmodial, anticataract, antifertility, wound healing, antiinflammatory, antinociceptive, antihyperglycemic, anthelmintic, diuretic, antitussive, antiglaucoma, antiallergic, and larvicidal activity. In conclusion, in vitro studies with animal models seem to show the potential beneficial effects of H. indicum against a wide variety of disorders and as a source of phytotherapeutic compounds. However, clinical studies are necessary to confirm the effects observed in animal models, determine the toxicity of the therapeutic dose and isolate the truly bioactive components.

Diuretic activities of hydro-alcoholic extract and solvent fractions of the roots of Withania somnifera L. (Solanacaea) in rats

Background: Withania somnifera (Local name ‘Gsawa’) is used in folkloric medicine for the management of hypertension in different parts of the world including Ethiopia. This may be due to its diuretic activity. However, it has not been yet scientifically validated for its efficacy and safety. Objective: The aim of this study was to investigate the diuretic potential of both hydro-alcoholic (80% methanol) extract and solvent fractions of the hydro-alcoholic root extract of W. somnifera in rats. Results: The hydro-alcoholic extract increased diuresis significantly at the doses of 400 and 600mg/kg (p<0.05). Similarly, the solvent fractions of the hydro-alcoholic extract -the aqueous and n-butanol fractions- significantly increased urine volume at 400mg/kg (p<0.05). Regarding electrolyte excretion, the larger doses of both hydro-alcoholic extract and aqueous fraction increased natriuresis (p<0.05). Phytochemical analysis revealed the presence of secondary metabolites including tannins, terpenoids, flavonoids and saponins, which could be the responsible component (s) for the diuretic activity. Conclusion: The results of the present study indicated that the W. somnifera extract is endowed with significant diuretic activity providing evidence for its traditional claim. The increased diuresis effects of the crude extracts and fractions may be attributable for presence of polar phytoconstitutents. Background: Withania somnifera (Local name ‘Gsawa’) is used in folkloric medicine for the management of hypertension in different parts of the world including Ethiopia. This may be due to its diuretic activity. However, it has not been yet scientifically validated for its efficacy and safety. Objective: The aim of this study was to investigate the diuretic potential of both hydro-alcoholic (80% methanol) extract and solvent fractions of the hydro-alcoholic root extract of W. somnifera in rats. Results: The hydro-alcoholic extract increased diuresis significantly at the doses of 400 and 600mg/kg (p<0.05). Similarly, the solvent fractions of the hydro-alcoholic extract -the aqueous and n-butanol fractions- significantly increased urine volume at 400mg/kg (p<0.05). Regarding electrolyte excretion, the larger doses of both hydro-alcoholic extract and aqueous fraction increased natriuresis (p<0.05). Phytochemical analysis revealed the presence of secondary metabolites including tannins, terpenoids, flavonoids and saponins, which could be the responsible component (s) for the diuretic activity. Conclusion: The results of the present study indicated that the W. somnifera extract is endowed with significant diuretic activity providing evidence for its traditional claim. The increased diuresis effects of the crude extracts and fractions may be attributable for presence of polar phytoconstitutents. Background: Withania somnifera (Local name ‘Gsawa’) is used in folkloric medicine for the management of hypertension in different parts of the world including Ethiopia. This may be due to its diuretic activity. However, it has not been yet scientifically validated for its efficacy and safety. Objective: The aim of this study was to investigate the diuretic potential of both hydro-alcoholic (80% methanol) extract and solvent fractions of the hydro-alcoholic root extract of W. somnifera in rats. Results: The hydro-alcoholic extract increased diuresis significantly at the doses of 400 and 600mg/kg (p<0.05). Similarly, the solvent fractions of the hydro-alcoholic extract -the aqueous and n-butanol fractions- significantly increased urine volume at 400mg/kg (p<0.05). Regarding electrolyte excretion, the larger doses of both hydro-alcoholic extract and aqueous fraction increased natriuresis (p<0.05). Phytochemical analysis revealed the presence of secondary metabolites including tannins, terpenoids, flavonoids and saponins, which could be the responsible component (s) for the diuretic activity. Conclusion: The results of the present study indicated that the W. somnifera extract is endowed with significant diuretic activity providing evidence for its traditional claim. The increased diuresis effects of the crude extracts and fractions may be attributable for presence of polar phytoconstitutents.

Chemical Composition, Diuretic, and Antityrosinase Activity of Traditionally Used Romanian Cerasorum stipites.

Cherry stems (CS) represent a by-product intensively used in Eastern European countries as a traditional remedy for urinary tract disorders. Ethnopharmacological evidences sustain the use of CS as aqueous preparations (infusion and decoction), but few data were previously reported about phytochemical profile and pharmacological potential of CS hydroalcoholic extracts. In this regard, we aimed to evaluate the phenolic profile, in vitro antioxidant and tyrosinase inhibitory potential, and in vivo diuretic activity of 70% hydroethanolic cherry stems extract and cherry stems decoction (CSD). LC-DAD-ESI/MSn analysis revealed the presence of flavonoid-type compounds as main constituents for both preparations, especially flavanones (naringenin glycosides). Antioxidant activity evaluated through DPPH, ABTS, and FRAP methods was superior for cherry stems extract, probably due to the presence of phenolic-derived compounds in higher amounts than CSD. On the other hand, tyrosinase inhibitory potential and diuretic effect exerted by CSD were stronger, highlighting that other types of hydrophilic secondary metabolites are responsible for this bioactivity. Overall, our findings indicate that CS preparations could be used as promising mild diuretic agents and encourage further investigations regarding the correlation between their chemical composition and bioactive potential.

Гостра токсичність і діуретична активність похідних аміно-3-метилксантинів

A vital problem of the contemporary pharmacology lies in creation of safer and more efficient medicinal products. Regulation of sodium balance and water being one of the important homeostatic functions is essential for developing the methods of rational therapy through means of diuretics of renal function of kidneys. This work is aimed to study the dependence of acute toxicity and diuretic activity on chemical structure of the newly synthesized 7-substituted-8-amino-3-methylxanthines in experiments on rats. The acute toxicity of 7-(2-hydroxy-3-p-methoxyphenoxy) propyl-8-substituted theophylline has been studied on the intact white nonlinear mice weighing 20-24 LD50 and has been calculated according to the method of Korber. The study of the diuretic activity of the above-mentioned compounds has been carried out on white rats of Wistar line weighing 180-195g according to the method of Y.B. Berkhina. The gained outcome of research into the acute toxicity of 7-substituted-8-amino-3-methylxanthines (compounds 1-11) has shown that LD50 of the synthesized compounds is in the range from 290 to 835 mg/kg. The most toxic (LD50=290 mg/kg) compound is the 6th one: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-n-butylaminoethyl. Substitution in the 8th position of the molecule of 7-substituted-8-amino-3-methylxanthines n-butylamine (compound 6) of radical with 4-benzylpiperazine-1-ilne (compound 11), p-ethoxyphenyl-amic (compound 10) N,N-diethylaminoethylamine (compound 4), 4-methylpiperazine-1- ilne (compound 1), N,N-diethylaminoethylamine (compound 3), N-methyl-N-benzylamine (compound 2), (pyrrolidine-1- ilne (compound 7), m-tolylamine (compound 9), β-hydroxyethylepiperazine-1- ilne (compound 8), (furil-2)methylamine (compound 5) causes a reduction of the acute toxicity of the aforesaid substances. Analysis of the diuretic activity research shows that derivatives of 7-substituted-8-amino-3-methylxanthines (compounds 1-11) increases excretion of urine in the range from 25.1% to 201.4% (p<0.05). The most signifying diuretic activity has been shown by the compound 5: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-(furil-2)methylaminoxanthine, which in the dose of 41.8 mg/kg enhances the water diuresis for 201.4% (p<0.01). Introduction to the 8th position of the molecule of 7-substituted-8-amino-3-metylxanthines instead of furil-2-methylamine (compound 5) radical of m-tolylamine (compound 9), n-butylamine (compound 6) and p-ethoxyphenylamine (compound 10) fragments leads to a reduction in renal excretory function for 143.5%; 131.8% and 111%, accordingly. Hydrochlorothiazide in the dose of 25 mg/kg enhances the water diuresis for 90.1%. Thus, the most signifying diuretic effect is observed in the compound 5, which exceeds the effect of the hydrochlorothiazide for 111.3% (p<0.05) and has been selected for further study of the specific activity.

Hog plums: Its importance, potentials and future prospects

Hog plums, scientifically known as Spondias mombin are medicinal plants that are rich in nutrients and antioxidants, and are of great importance in the food/agricultural industries and the health sector. In the food industries, it is an important fruit crop that can be eaten raw, juiced and processed for making jam, ice cream and jellies, and also provides farmers an alternative feeding material for lactating ruminants to help in galactogenesis and lactopoiesis. In the health sector, hog plums fruit, leaves and stem extract possess antimicrobial, cytotoxic, anti-tyrosinase, diuretic and febrifuge activities for the treatment of certain disease conditions, and it can be effectively preserved by wax coating of the fruits. Methanolic extract of Spondias contain methyl gallate, a substance that has the potential to facilitate apoptotic cell death in human glioblastoma, lung, and breast cancer Hog plums are also rich in vitamins, it strengthens the immune system, protects against heart disease, and stimulates the production of collagen which keeps the body healthy. It is a plant that has obvious and promising health benefits, and as such more research into its properties is advisable. Preservation of hog plum can be achieved by wax coating, retardation of ripening and senescence, and application of growth regulators.

Torasemide in Hypertension and Heart Failure: Re-inventing Loop Diuretic Therapy?

In heart failure (HF) patients, current European Society of Cardiology (ESC) guidelines recommend the use of three loop diuretics (furosemide, torasemide, bumetanide) in order to not only reduce HF hospitalizations but also improve symptoms and exercise capacity in patients with signs and/or symptoms of congestion. In addition, for the first time in hypertensive patients, European Society of Hypertension (ESH) guidelines recommend the use of torasemide. This review aimed to summarize the mode of action of loop diuretics, to present their pharmacokinetic characteristics, and to discuss their place in the management of arterial hypertension and heart failure, with special emphasis however on torasemide.

Diuretic Activity of Indian Medicinal Plant: A Review

Diuretics are commonly defined as drugs that increase the amount of urine produced by kidney. A precise definition is that diuretics are the agent which augment the renal excretion of sodium and either chloride or bicarbonate primarily, and water excretion secondarily. The term “saluretic” is sometime used to describe a drug that increase the renal excretion of sodium and chloride ion Diuretics are responsible for increase the rate of urine flow, sodium excretion and to maintain the volume and composition of body fluids in a various clinical Disorders. But drug-induced diuresis is very much beneficial in such type of life-threatening disorders like CHF, hypertension, renal failure, Liver cirrhosis and often pregnancy toxaemia.[1] Diuretics relieve pulmonary congestion and peripheral edema. This decreases cardiac workload, oxygen demand and plasma volume, thus decreasing blood pressure. Thus, diuretics play an important role in hypertensive patients.[2] Plant medicine is commonly used in the traditional treatment of some renal diseases, and many plants are reported to possess significant diuretic activity. The diuretic activity of a number of plants used in ethno medicine as diuretic agents has been confirmed in experimental animal. [3]The progress of a polyherbal formulation is a tough job because of the large number of different chemical compounds present in the different medicinal plants.

Antihypertensive Activities of Standardised Moringa oleifera Lam (Merunggai) Extracts in Spontaneously Hypertensive Rats

In recent years, Moringa oleifera has received commercial interest for its blood pressure (BP)-lowering effect. The objectives of this study were to investigate the hypotensive, diuretic, and angiotensin converting enzyme (ACE)-inhibitory activities of M. oleifera ethanolic and aqueous extracts. Spontaneously hypertensive (SH) and normotensive (NT)rats were fed the ethanolic and aqueous extracts at a dose of 1000 mg/kg each for 14 days. The rats were allocated to 12 groups of five rats each. Systolic and diastolic BP were measured, and urine was collected. All extracts, except the aqueous stem extract, significantly reduced systolic and diastolic BP in SH rats, but none of the extracts showed significant hypotensive effects on NT rats. The ethanolic leaf extract (ELE) caused significant diuresis. Moreover, most of the extracts inhibited ACE activity significantly at 40 and 80 μg/mL. ELE, aqueous leaf extract (ALE), and ethanolic pod extract (EPE) showed the highest levels of inhibition (&gt;50%), and their IC50 values; ELE (58.65±1.55), ALE (71.35±1.00) and EPE (54.04±1.00) were determined. The hypotensive effect observed was achieved either by diuretic or ACE-inhibitory activity. The active extracts are worthy of further investigation, as they have the potential to be developed as dietary supplements for pre-hypertensive individuals.

Diuretic Action of Apelin-13 Mediated by Inhibiting cAMP/PKA/sPRR Pathway.

Emerging evidence is showing that apelin plays an important role in regulating salt and water balance by counteracting the antidiuretic action of vasopressin (AVP). However, the underlying mechanism remains unknown. Here, we hypothesized that (pro) renin receptor (PRR)/soluble prorenin receptor (sPRR) might mediate the diuretic action of apelin in the distal nephron. During water deprivation (WD), the urine concentrating capability was impaired by an apelin peptide, apelin-13, accompanied by the suppression of the protein expression of aquaporin 2 (AQP2), NKCC2, PRR/sPRR, renin and nuclear β-catenin levels in the kidney. The upregulated expression of AQP2 or PRR/sPRR both induced by AVP and 8-Br-cAMP was blocked by apelin-13, PKA inhibitor (H89), or β-catenin inhibitor (ICG001). Interestingly, the blockage of apelin-13 on AVP-induced AQP2 protein expression was reversed by exogenous sPRR. Together, the present study has defined the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/sPRR pathway in the CD as the molecular target of the diuretic action of apelin.

Antiadhesive activity of hydroethanolic extract from bean pods of Phaseolus vulgaris (common bean) against uropathogenic E. coli and permeability of its constituents through Caco-2 cells monolayer

Ethnopharmacological relevancePhaseaoli pericarpium (bean pods) is a pharmacopeial plant material traditionally used as a diuretic and antidiabetic agents. Diuretic activity of pod extracts was reported first in 1608. Since then Phaseoli pericarpium tea figures in many textbooks as medicinal plant material used by patients. Aim of the studyDespite the traditional use of extracts from Phaseolium vulgaris pericarp, limited information is available on bioactivity, chemical composition, and bioavailability of such preparations. The following study aimed to investigate the phytochemical composition, the in vitro permeability of selected extract's constituents over the Caco-2 permeation system, and potential antivirulence activity against uropathogenic Escherichia coli of a hydroalcoholic Phaseoli pericarpium extract (PPX) in vitro to support its traditional use as a remedy used in urinary tract infections. Material and methodsThe chemical composition of the extract PPX [ethanol:water 7:3 (v/v)] investigated by using UHPLC-DAD-MSn and subsequent dereplication. The permeability of compounds present in PPX was evaluated using the Caco-2 monolayer permeation system. The influence of PPX on uropathogenic E. coli (UPEC) strain NU14 proliferation and against the bacterial adhesion to T24 epithelial cells was determined by turbidimetric assay and flow cytometry, respectively. The influence of the extract on the mitochondrial activity of T24 host cells was monitored by MTT assay. ResultsLC-MSn investigation and dereplication, indicated PPX extract to be dominated by a variety of flavonoids, with rutin as a major compound, and soyasaponin derivatives. Rutin, selected soyasaponins and fatty acids were shown to permeate the Caco-2 monolayer system, indicating potential bioavailability following oral intake. The extract did not influence the viability of T24 cells after 1.5h incubation at 2 mg/mL and UPEC. PPX significantly reduced the bacterial adhesion of UPEC to human bladder cells in a concentration-dependent manner (0.5–2 mg/mL). Detailed investigations by different incubation protocols indicated that PPX seems to interact with T24 cells, which subsequently leads to reduced recognition and adhesion of UPEC to the host cell membrane. ConclusionsPPX is characterised by the presence of flavonoids (e.g. rutin) and saponins, from which selected compounds might be bioavailable after oral application, as indicated by the Caco-2 permeation experiments. Rutin and some saponins can be considered as potentially bioavailable after the oral intake. The concentration-dependent inhibition of bacterial adhesion of UPEC to T24 cells justifies the traditional use of Phaseoli pericarpium in the prevention and treatment of urinary tract infections.

Phytochemical profile and diuretic activity of the bearberry leaves dry extracts

More than 150 million cases of infectious diseases of the urinary system are registered annually in the world. Common bearberry (Arctostaphylos uva-ursi L.) leaves is one of the most well-known species of raw materials with uroantiseptic and diuretic activity. The method of a decoction obtaining from bearberry leaves is well known, but this dosage form is non-standardized, poorly stored and difficult to maintain the accuracy of dosing. In this regard, the development of domestic standardized medicines based on bearberry leaves is an urgent aim of modern pharmacy.&#x0D; The aim of the research is to study the phytochemical profile and pharmacological activity of the bearberry leaves dry extracts, obtained by various extractants, to identify the most promising substance with diuretic and uroantiseptic activity.&#x0D; Materials and methods. The subjects were the dry extracts obtained from bearberry leaves with purified water and ethanol solutions (30 %, 50 %, 70 % and 96 %). Determination of the main BAS extracts was performed by TLC, HPLC and spectrophotometry. Determination of diuretic activity of the extracts was performed by the method of E. B. Berchin, antibacterial activity – by diffusion into agar.&#x0D; Results. Arbutin, 2 phenolic acids, 6 flavonoids and 8 saponins were detected in the bearberry extracts. The results showed that arbutin and saponins are better extracted with water and diluted solutions of ethanol, while phenolic acids and flavonoids – with 50–70 % ethanol. As a result of studying the diuretic activity of the bearberry extracts, it was found that the highest diuretic activity has the extract obtained with 50 % ethanol at a dose of 50 mg/kg, increasing diuresis by 70 %. The bearberry leaves extracts showed activity against S. aureus, E. coli, P. vulgaris, P. aeruginosa, B. subtilis and C. albicans. The content of different groups of phenolic compounds, economic factor and pharmacological activity showed that 50 % ethanol is the optimal extractant for extraction phenolic compounds from bearberry leaves and creation of new medicines from the raw materials.&#x0D; Conclusions. As a result of phytochemical and pharmacological studies, it was found that the dry bearberry leaves extract obtained with 50 % ethanol solution was the most promising substance with diuretic and uroantiseptic action

Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities

One of the most important tasks of our indigenous pharmaceutical science is the necessity for new medicines because existing drugs are characterized by various side effects, resistance, high toxicity, and so on. New bioactive molecule synthesis utilizes substances of natural origin as well as chemically modified ones. Thus, the researcher’s attention is mainly focused on 3-,7-,8-substituted derivatives of the natural heterocyclic xanthine system, which possess a wide range of pharmacological action. Synthesis of a novel of (3-benzyl-8-propylxanthin-7-yl)acetohydrazides with antimicrobial and diuretic activities described in the paper.&#x0D; The aim of this work is to develop efficient methods for synthesis of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives, and to study their physical-chemical properties.&#x0D; Materials and methods. Two-hour boiling of propyl 2-(3-benzyl-8-propylxanthine-7-yl)acetate by excess hydrazine hydrate in propan-2-ol medium have yielded the key the key intermediate 2-(3-benzyl-8-propylxanthine-7-yl)acetohydrazide. Further transformation of the latter has led to formation of corresponding acetohydrazide derivatives achieved by the reaction with aliphatic, aromatic, heterocyclic aldehydes, and ketones. The structure and the relative configuration of the synthesized compounds were elucidated by analyzing their physical-chemical data.&#x0D; Results. The synthesis and optimization of reaction conditions of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives were conducted. The identification of all synthesized compounds was aided by various physical-chemical methods (thin layer chromatography, elemental analysis, IR, and 1H NMR spectroscopy).&#x0D; Conclusions. As a result of synthetic research the preparative synthesis method of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives possessing antimicrobic, and diuretic activities was developed.

Combination therapy of midodrine and droxidopa for refractory hypotension in heart failure with preserved ejection fraction per a pharmacist\u2019s proposal: a case report

BackgroundPatients with chronic heart failure (CHF) are often treated using many diuretics for symptom relief; however, diuretic use may have to continue despite hypotension development in these patients. Here, we present a case of heart failure with preserved ejection fraction (HFpEF), which is defined as ejection fraction ≥50% in CHF, and refractory hypotension, which was treated with midodrine and droxidopa to normalize blood pressure.Case presentationThe patient was a 62-year-old man with a history of HFpEF due to mitral regurgitation and complaints of dyspnea on exertion. He had been prescribed multiple medications at an outpatient clinic for CHF management, including azosemide 60 mg/day, bisoprolol 2.5 mg/day, enalapril 2.5 mg/day, spironolactone 50 mg/day, and tolvaptan 15 mg/day. The systolic blood pressure (SBP) of the patient remained at 70–80 mmHg because the use of the diuretic could not be reduced or discontinued owing to edema and weight gain. He was hospitalized for the exacerbation of CHF. Although midodrine 8 mg/day was administered to improve hypotension, the SBP of the patient increased only up to 90 mmHg. On the 35th day after hospitalization, the urine volume decreased significantly (< 100 mL/day) due to hypotension. When droxidopa 200 mg/day replaced intravenous noradrenaline on the 47th day, the SBP remained at 100–120 mmHg and the urine volume increased.ConclusionsOral combination treatment with midodrine and droxidopa might contribute to the maintenance of blood pressure and diuretic activity in HFpEF patients with refractory hypotension. However, further long-term studies evaluating the safety and efficacy of this combination therapy for patients with HFpEF are needed.