Diuretic Activity Research Articles

ZIF@ZnTiO3 Nanocomposite as a Reusable Organocatalyst for the Synthesis of 3, 4-dihydropyrano[c]chromene Derivatives

Background: Dihydropyrano [3, 2-c]chromenes and their derivatives have great attention for scientists. They have different activities such as biological properties, spasmolytic, diuretic, anticoagulant, anti-cancer, and anti-anaphylactic activity. For these vary biological activities, chromene derivatives have made significant for further progress in medicinal and organic synthesis studies. So, in view of the importance of chromenes, we aimed to synthesis of 3, 4-dihydropyrano [3, 2-c] chromene derivatives. ZIF@ZnTiO3nanocomposite as organocatalyst was used. Method: An effective and applicable technique was used for preparation of 3, 4-dihydropyrano [3, 2- c] chromene derivatives. Dihydropyrano [c] chromenederivatives were prepared by using ZIF@ZnTiO3compositeas a recyclable catalyst. One-pot three-component reaction of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin was done for synthesis of dihydropyrano [c] chromenederivatives over composite catalyst with excellent yields. The as prepared dihydropyrano [c] chromenederivatives were measured by melting point, FTIR, 1H NMR, and 13C NMR. The nano catalyst could be recycled several times. Result: A novel nano catalyst of MOF containing Mn2+ ions and 2- methyl imidazole (ZIF) and zinctitanate (ZIF@ZnTiO3) composite was prepared. The synthesized organocatalyst was studied for preparation of 3, 4-dihydropyrano [3, 2-c] chromene derivatives. One-pot three-component reaction of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin was done for synthesis of dihydropyrano [c] chromene derivatives over composite catalyst with excellent yields. The reaction was optimized. Conclusion: The organocatalyst composite of consist of ZIF and zinctitanate was prepared. The ZIF@ZnTiO3 was used as catalyst for synthesis of 3, 4-dihydropyrano [3, 2-c] chromene derivatives via one-pot three-component condensations of aromatic aldehydes,malononitrile, and 4 hydroxycoumarin. The results of melting point, FTIR, 1H NMR, 13C NMR also confirmed the formation of high yield of 3, 4-dihydropyrano [3, 2-c] chromene derivatives at short time. The appealing properties of this method are environmentally friendly, mild reaction conditions (low reaction time and high yields of pure products), easy work up and recyclability of reaction catalyst.

Działanie moczopędne wybranych surowców roślinnych

Goldenrod herb (Solidago virgaurea L.), birch leaves (Betula pendula Roth) and lovage radix (Levisticum officinale Koch.) have a long history of use as a traditional herbal medicinal product. These herbal substances are part of many products intended for use in the case of diseases of the urinary tract. Among many activities, plants as lovage, birch and goldenrod are known for their diuretic activity. The mechanism of this action has not been thoroughly understood and explained so far. There are also few clinical research studies confirming such properties of the herbal substances described. This article describes information on this subject available in the literature.

Diuretic Activity of a Novel Peripherally-Restricted Orally-Active Kappa Opioid Receptor Agonist.

Kappa-opioid agonists (KOAs) enhance cardiac performance, as well as reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis; however, there has been limited development of KOAs as a class due to the promotion of untoward central nervous system (CNS)-mediated side effects. Our laboratory has developed a peripherally-restricted, orally-active, KOA (JT09) for the treatment of pain and cardiovascular disease. Peripherally-restricted KOAs possess a limited side-effect profile and demonstrate potential in preventing heart failure. The aim of this study was to assess the diuretic activity of lead compound JT09 relative to vehicle control and Tolvaptan through single oral administration to adult male Sprague–Dawley rats. JT09-administered rats demonstrated significantly increased urine output relative to vehicle control. However, the effect persisted for 8 h, whereas Tolvaptan-administered rats demonstrated diuretic activity for 24 h. Relative to Tolvaptan, urine output was significantly reduced in JT09 administered animals at all-time points, suggesting that the overall diuretic effect of JT09 is less profound than Tolvaptan. Additionally, JT09-administered rats demonstrated alterations in clinical chemistry; reduced urine specific gravity; and increased urine pH relative to vehicle control. The following study establishes a preliminary diuretic profile for JT09.

An updated comprehensive review of the medicinal, phytochemical and pharmacological properties of Moringa oleifera

Moringa oleifera Lam, or the horse-radish tree as it is commonly called is a pan-tropical species that has now become naturalized in Afghanistan, Florida and East and West Africa. In addition to its exceptional nutritional value in various parts of the world, M. oleifera is well-known for the substantial medicinal benefits that it offers. Scientific studies over the past few decades have substantiated many of the traditional folklore claims of the medicinal uses of morphological parts of M. oleifera for various ailments such as heart complaints, fevers, inflammation, digestive disorders, headaches, asthma, intestinal complaints and rheumatism. Moringa oleifera possesses many pharmacological attributes such as analgesic, anti-inflammatory, diuretic, antihypertensive, antioxidant and anti-tumor activities. In addition, M. oleifera also contains several phytochemicals, some of which are of high interest because of their medicinal value. Every part of M. oleifera is said to have beneficial properties which contribute to its diversity and value as a medicinal plant. This review will present an updated compilation of the published scientific evidence on the medicinal attributes, phytochemical composition and recent advances in pharmacognosy of M. oleifera.

Diuretic activity of ethanol extract of Mirabilis jalapa (Linn.) leaf in normal male Wistar rats

Background: Ethanol extract of Mirabilis jalapa leaf (EEMJL) has been used in the folk medicine of Nigeria as diuretics without any scientific evidence.Aim: Ethanol extract of Mirabilis jalapa leaf at 200, 400 and 600 mg/kg body weight was investigated for diuretic activity in male Wistar rats.Setting: Fresh leaf of M. jalapa was collected from a farmland at the Alanamu area in Ilorin, Kwara State, Nigeria, authenticated and processed for the study.Methods: Thirty male rats (231.50 g ± 13.51 g) were assigned into five groups (A–E) of six rats each. Rats in group A (control) received 1.0 mL of physiological saline (the vehicle). Animals in groups B (positive control), C, D and E received 1.0 mL equivalent to 100 mg/kg body weight of furosemide, 200, 400 and 600 mg/kg body weight of EEMJL, respectively. All administrations were done by oral gavage. The animals were monitored for indicators of diuresis for 5 h using standard methods.Results: Ethanol extract of Mirabilis jalapa leaf dose-dependently increased (p < 0.05) urine volume, urine concentrations of Na+, K+ and Cl− and decreased (p < 0.05) the body weight of the animals. Ethanol extract of Mirabilis jalapa leaf increased the urine pH, saliuretic activity, saliuretic index, Na+ index, K+ index, Cl− index, diuretic action (diuretic index), kaliuretic index, Lipschitz value and percentage saline load excreted, whereas the latency of urination, natriuretic index, carbonic anhydrase inhibitory activity and carbonic anhydrase inhibition index were decreased. The EEMJL treatment-related changes in these parameters were essentially similar to those of the furosemide-treated animals.Conclusion: This study has thus validated diuretic activity of M. jalapa leaf with the 600 mg/kg body weight of EEMJL being the most effective.

A four-step filtering strategy based on ultra-high-performance liquid chromatography coupled to quadrupole-time-of-flight tandem mass spectrometry for comprehensive profiling the major chemical constituents of Akebiae Fructus.

Akebiae Fructus (AF) is a traditional Chinese medicine (TCM) with antiphlogistic, analgesic, antineoplastic, diuretic, antirheumatic, antidepressant and antiobesity activities. Identification of chemical constituents from AF is helpful to discover the potential active ingredients and to control its quality. The four-step filtering strategy was as follows: (1) To extract the accurate mass by the different adduct ions. (2) To screen different types of the compounds using diagnostic ions. (3) By characteristic ion filtering, to confirm the substituted position and the sugar chain numbers. (4) Based on the neutral loss (NL), to identify the type of monosaccharide and the compositions of sugar chains of triterpenoid saponins and the structure of CGAs. A total of 94 compounds (85 triterpenoid saponins, 9 chlorogenic acids) were unambiguously or reasonably identified. Fifty constituents were discovered for the first time from AF. Nine types of triterpenoid saponins, including akebonoic acid (type I), norhederagenin (type II), oleanolic acid (type III), 2α,3β-dihydroxy-23-oxo-30-norolean-12,20(21)-dien-28-oic acid (type IV), gypsogenin (type V), norarjunolic acid (type VI), hederagenin (type VII), 2α,3β-dihydroxy-23-oxo-olean-12-en-28-oic acid (type VIII), arjunolic acid (type IX), and two types of chlorogenic acid (mono-CQA and di-CQA), were identified in AF. An ultra-high-performance liquid chromatography coupled to quadrupole-time-of-flight tandem mass spectrometry with MSE (UPLC-QTOF-MSE ) analysis with four-step filtering strategy was established and successfully applied to identify the chemical constituents of AF which can provide chemical support for further research and play an important role in the quality control of AF.

The effectiveness of the use of herbal drugs in the complex treatment of patients with acute uncomplicated pyelonephritis

The objective: to study the effect of herbal medicine Canephron ® N in the treatment of patients with uncomplicated pyelonephritis and to prevent the recurrence of infectious and inflammatory complications.Materials and methods. 73 patients with uncomplicated pyelonephritis were examined on the basis of the city clinical hospital of emergency and emergency medical care in Zaporozhye (urology department). The method of random distribution of patients were divided into two groups. The control group included 36 patients, the main group included 37 patients with uncomplicated pyelonephritis. The control group of patients received a comprehensive anti-inflammatory therapy. The main group received anti-inflammatory complex therapy and the herbal preparation Canephron ® N, 2 tablets 3 times a day, starting from the first day of hospital stay. According to the protocol for the treatment of this pathology, all patients underwent a standard examination, which included clinical and laboratory examination, ultrasound, and radiographic examinations.Results. In the control group, a decrease in the infectious-inflammatory process after treatment was observed for 12.5 days. Relapse of pyelonephritis after discharge from the hospital was recorded in 47.2% of patients for a year. In the main group, a decrease in the infectious- inflammatory process after discharge from the hospital and a comprehensive anti-inflammatory therapy with herbal medicine Canephron® H was observed on the seventh day. Recurrence of pyelonephritis during the year after discharge from the hospital was observed in 24.3% of patients.Conclusion: The prescription of herbal medicine Canephron ® N, in addition to complex anti-inflammatory therapy, reduces the risk of relapse of infectious and inflammatory complications by half, which is caused by diuretic, anti-inflammatory and antimicrobial action.

Relationship between 25(OH) vitamin D and the number of antihypertensive drugs in hypertensive patients in the area of Blida (Algeria)

The purpose of the study was to evaluate the relationship between 25(OH) vitamin D and the number of antihypertensive drugs (AHTs) used in hypertensive patients. A total of 1145 patients were enrolled in the study between January 2017 and June 2018 in specialized consultation at the department of internal medicine at the Blida university hospital (65.8% female, 34.2% male, age: 52 ± 13 years old). The initial serum 25 (OH) vitamin D level was determined by the enzyme immunoassay for all patients. Antihypertensive therapy was supplemented with 200000 IU/month cholecalciferol for all the patients. A follow-up visit was performed 12 months later. In total, 22.4% of patients received 1 antihypertensive drug, 47.7% of patients 2 drugs, 19.7% of patients 3 drugs, 8.8% of patients 4 drugs, and 1.4% were treated with 5 antihypertensive drugs. The mean number of antihypertensive drugs was 2.5. Glomerular filtration measured by CKD-EPI was 49.3 ± 7.2 ml/min. The mean level of baseline plasma vitamin D was 10.6 ± 5.4 ng/ml. One year later, the mean plasma level of vitamin D increased to 28.3 ± 10.8. Sixty seven percent of the patients were still under vitamin D supplementation at follow-up whereas 32.8% had stopped the treatment. In the former, plasma vitamin D increased to 29.0 ng/ml versus 15.3 ng/ml in the latter group. There was a significant relationship between the 25(OH) vitamin D plasma level and blood pressure ( P = 0.05) and the number of antihypertensive drugs used ( P = 0.013). The difference between those patients who kept the treatment and those who stopped was highly significant ( P < 0.05). The action of diuretics on BP is more synergistic in combination with vitamin D (95.5% vs. 76.4% without vitamin D), followed respectively by calcium channel blockers (67.8% vs. 57.4%), beta-blockers (66.2% vs. 46.5%), converting enzyme inhibitors (50.3% vs. 34.4%) and finally angiotensin II receptor blockers (45.1% vs. 36.2%). The number of antihypertensive drugs have a less significant effect on PA in compared to groups with vitamin D ( P < 0.001). Supplementation with vitamin D improved the control of BP in our studied population. It seems desirable to encourage the prescription of a dual therapy containing a diuretic in hypertensive patients with supplementation in vitamin D. Further studies are necessary to better explore the plasma level of vitamin D and the efficiency of different classes of antihypertensive treatment.

Anti-inflammatory and diuretic effects of the diterpene ent-dihydrotucumanoic acid.

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 μg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 μg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 μg/mL (TNF-α) and 58.12 μg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1β (36%) was recorded at 200 μg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.

A thienopyridine, CB-20, exerts diuretic activity by inhibiting urea transporters.

Urea transporters (UTs) are transmembrane proteins selectively permeable to urea and play an important role in urine concentration. UT-knockout mice exhibit the urea-selective urine-concentrating defect, without affecting electrolyte balance, suggesting that UT-B inhibitors have the potential to be developed as novel diuretics. In this study, we characterized a novel compound 5-ethyl-2-methyl-3-amino-6-methylthieno[2,3-b]pyridine-2,5-dicarboxylate (CB-20) with UT inhibitory activity as novel diuretics with excellent pharmacological properties. This compound was discovered based on high-throughput virtual screening combined with the erythrocyte osmotic lysis assay. Selectivity of UT inhibitors was assayed using transwell chambers. Diuretic activity of the compound was examined in rats and mice using metabolic cages. Pharmacokinetic parameters were detected in rats using LC–MS/MS. Molecular docking was employed to predict the potential binding modes for the CB-20 with human UT-B. This compound dose-dependently inhibited UT-facilitated urea transport with IC50 values at low micromolar levels. It exhibited nearly equal inhibitory activity on both UT-A1 and UT-B. After subcutaneous administration of CB-20, the animals showed polyuria, without electrolyte imbalance and abnormal metabolism. CB-20 possessed a good absorption and rapid clearance in rat plasma. Administration of CB-20 for 5 days did not cause significant morphological abnormality in kidney or liver tissues of rats. Molecular docking showed that CB-20 was positioned near several residues in human UT-B, including Leu364, Val367, and so on. This study provides proof of evidence for the prominent diuretic activity of CB-20 by specifically inhibiting UTs. CB-20 or thienopyridine analogs may be developed as novel diuretics.

Sulfa drug analogs: new classes of N-sulfonyl aminated azines and their biological and preclinical importance in medicinal chemistry (2000–2018)

N-sulfonylamino azinones has attracted the interest of numerous researchers and extensive investigations on their biological activities have been done. The present review provides an overview of the patents and reports filed during the last few years pertaining to the synthesis N-sulfonyl azinones as well as their biological and preclinical studies. A brief discussion on the significant biological findings is also provided. It has been established that N-sulfonylamino azinones is privileged heterocycles possessing diuretic, antihypertensive, anti-inflammatory, and anticancer and other biological activities. In particular, a new generation of competitive AMPA receptor antagonist based on N-sulfonylamino 1H-quinazoline-2,4-diones is promising useful in the treatment neurological disorders such as epilepsy and schizophrenia. The scope of these new advances has been also highlighted in this review.

Synthesis, diuretic activity research and QSAR-analysis of N-(1,3,4-tiadiazol-2-il)substituted amides of alkanecarboxylic acids

Diuretics are effective drugs that are widely used in medicine, but have unwanted side effects. The derivative of thiadiazole – acetozolamide is a known diuretic. Therefore, the search for diuretics in this series and the establishment of quantitative «structure–activity» (QSAR) dependencies is appropriate.&#x0D; The aim of the work was to synthesis N-(1,3,4-thiadiazol-2-yl)substituted alkanes of alkanecarboxylic acids, study their diuretic activity, and QSAR analysis.&#x0D; The objects of the study were N-(1,3,4-thiadiazol-2-yl)substituted alkanes of alkanecarboxylic acids, obtained by the interaction of 2-amino-5-alkyl-1,3,4-thiadiazole with the corresponding acylchlorides. Investigation of diuretic activity of synthesized compounds was carried out by the method of Berchin. Hyper-Chem and BuildQSAR software were used for calculation of molecular descriptors and QSAR-models.&#x0D; Synthesis of 12 N-(1,3,4-thiadiazol-2-yl)substituted amides of alkanecarboxylic acids, the structure of which was confirmed by PMR spectroscopy and elemental analysis. Studies of diuretic activity showed that the synthesized compounds had pronounced diuretic properties, and some of them according to activity indicators were approaching or exceeding comparative preparations. Compound N-(5-methyl-[1,3,4]thiadiazol-2-yl) propionamide showed the best diuretic effect: increased daily diuresis in white rats, in comparison with intact control, in 2.47 times (p ≤ 0,001), in comparison with hydrochlorothiazide was in 1,6 times and acetazolamide was 1,75 times. The calculation of the molecular descriptors of N-(1,3,4-thiadiazol-2-yl)substituted amides of alkanecarboxylic acids was conducted. Based on the calculated values of molecular descriptors and diuretic activity values of 12 synthesized compounds, a QSAR analysis was performed. Analysis of structure-diuretic activity showed the greatest influence of lipophilicity, energy parameters, spatial structure and size of the molecule. Moreover, diuretic activity increases with increasing logP, decreasing the refractive, volume and area of the molecule, increasing the energy of the higher occupied molecular orbital. Increasing the charge on the Sulfur atom of the thiadiazole ring and the Оxygen atom of the carbonyl group, reducing the angle between the Sulfur atoms, the Nitrogen of the amide group and the Oxygen, and increasing the angle between the Nitrogene atoms of the thiadiazole ring, the Oxygen and the Nitrogen of the amide group, also increases diuretic activity.&#x0D; The results of the diuretic activity of the synthesized compounds N-(1,3,4-thiadiazol-2-yl)substituted amides of alkanecarboxylic acids show the potential for the search for diuretic agents among 1,3,4-thiadiazole derivatives. The resulting QSAR models will be used to modelling and prediction the activity of new potential diuretics.

Report on Antidiabetic, Diuretic and Analgesic Activities of Methanolic Extract of Leaves of Strychnos colubrina L.an Endangered Medicinal Plant

Strychnos colubrina L. belongs to family Loganiaceae was known as snake wood tree.The methanolic extracts from Strychnos colubrina L. leave collected from different provinces in Penchalakona of Nellore district were prepared by decoction and maceration with methanol and evaluated for their antidiabetic, diuretic and analgesic activities. Methanolic extracts from Strychnos colubrina L. leaves (SCM) were evaluated for anti diabetic effect in Streptozocin (STZ) induced diabetes in rats. The blood sugar levels were analysed as indices of diabetes. 200 mg/kg b.w. of the extract showed a greater reduction in blood glucose level which was comparable to glibenclamide. To find out diuretic efficacy, SCM of leaves were administered to experimental rats orally at doses of 100 and 200 mg/kg and compared with Furosemide (20 mg/kg,o.p) as the standard. The rats treated with SCM of leaves in a dose of 200 mg/kg shown near similar urine output and electrolytes excretion when compared to the respective control. The analgesic activity of SCM of leaves is estimated using tail flick in mice. Results demonstrated that SCM of leaves exhibited a potent dose-dependent analgesic activity in all tested models for analgesia. This report could be used for medicinal and pharmaceutical exploration in the future.

A REVIEW ON PHARMACOLOGICAL ACTIVITY OF BENINCASA HISPIDA

Benincasa hispida is a well-known plant and is cultivated throughout the plains of india and on the hills upto 1200 meter altitude. It is a popular vegetable crop widely used for nutritional and medicinal properties especially in asian countries. Benincasa hispida fruit has been valued as a nutritious vegetable as it provide a good source for natural sugars,organic acid, amino acid,vitamins and mineral elements. Phytochemical constituents of this plant are mannitol, triterpenoids, cucurbitin, β-sitosterin, flavanoids, glycosides, carotenes, vitamins and uronic acid. The pharmacological studies revealed that the plant exerted many pharmacological activities such as antiulcer, antihyperlipidemic, antihelmintic, antioxidant, neuropharmacological activity, diuretic activity.&#x0D; Keywords: Benincasa hispida, antiulcer, diuretic, antihyperlipidemic, antihelminthic.

Diuretic effect and material basis of Clematidis Armandii Caulis in rats

To search for the active diuretic fractions of Clematidis Armandii Caulis( CAC) and determine its main active chemical components by using liquid chromatography-mass spectrometry( LC-MS) and diuretic activity evaluation. CAC 75% ethanol extracts and extracts from different polar solvents were orally administered to saline-loaded rats at different doses. 6 h urinary volume,p H and contents of electrolyte Na+,K+and Cl-were measured. The chemical components of the active fractions were separated and identified by ultra performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry( UPLC-ESI-Q-TOF-MS/MS) method. As compared with the control group,the urine volume was increased by 44%( P< 0. 01) and 34%( P < 0. 05) in CAC75% ethanol extract 57. 74 and 28. 8 mg·kg-1 groups respectively; the Na+excretion was increased by 52%( P< 0. 01) and 45%( P<0. 05),respectively; while the Cl-excretion was increased by 101%( P<0. 01) and 85%( P<0. 05),respectively. The urine volume,Na+excretion and Cl-excretion were increased by 50%( P< 0. 01),58%( P< 0. 05),and 65%( P< 0. 05) respectively in petroleum ether extract 70. 98 mg·kg-1 group as compared with the control group. While for the n-butanol extract 194. 18 mg·kg-1 group,the urine volume,Na+and Cl-excretion were increased by 42%( P<0. 01),41%( P<0. 05) and 97%( P<0. 01),respectively. The diuretic activity of other fractions was not obvious. There was no statistical difference in K+excretion in all groups. The results of LC-MS analysis showed that six compounds,including two sterols,one chromogen and three fatty acids,were identified from petroleum ether extract.Fourteen compounds,including six triterpenoid saponins,six lignin glycosides,one sterol glycoside and one phenolic glycoside,were identified from the n-butanol extract. All the results suggested that the ethanol extract of CAC had remarkable diuretic activity and its main effective components included sterol,triterpenoid saponin and lignin glycosides.

A comparative study of antidepressant and diuretic activity of semi-mild hawthorn liquid extracts

Introduction . The raw materials of the hawthorn plants (Crataegus L.) are flowers and fruits that are used as cardiotonic medicines. Leaves and shoots are prospective types of hawthorn raw materials. Currently, 12 species of hawthorn plants are used, but not all of them are widely grown on the territory of the Russian Federation. At the same time in our country is widely cultivated North American Quebec hawthorn - Crataegus submollis Sarg. The purpose of this work is a comparative study of the antidepressant activity and diuretic action of liquid extracts based on flowers, shoots, leaves and fruits of Quebec hawthorn. Materials and methods. The Desperation test was used to determine the antidepressant activity of liquid extracts based on flowers, fruits, shoots and leaves of Quebec hawthorn. Diuretic activity was determined in chronic experiments by collecting 4 and 24 hours portions of urine. Results. The study of the comparative antidepressant activity of liquid extracts based on flowers, leaves, shoots and fruits of Quebec hawthorn allowed to reveal antidepressant activity for all studied medicines comparable with amitriptyline at a dose of 5 mg/kg. In this liquid extracts of flowers, shoots and leaves of hawthorn semi-soft showed antidiuretic properties. Conclusions. Liquid extracts based on flowers, leaves, shoots and fruits of Quebec hawthorn have a neurotropic effect. Antidepressant activity of herbal preparations increases in the following series: liquid extract of Quebec hawthorn leaves - liquid extract of Quebec hawthorn fruits - liquid extract of Quebec hawthorn shoots - liquid extract of Quebec hawthorn flowers.

Diuretic activity and neuropharmacological effects of an ethanol extract from Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae)

Ethnopharmacological relevance Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a shrub empirically used as diuretic, and for the treatment of neurological disorders. These pharmacological effects have not been previously evaluated. Aim of the studyTo evaluate the diuretic and CNS effects of a standardized ethanol extract of Senna septemtrionalis aerial parts (SSE). Materials and methodsGas chromatography mass spectrometry was used to perform a chemical analysis with SSE. In all tests, SSE was evaluated from 10 to 100 mg/kg p.o.The diuretic activity of SSE was assessed in mice individually placed in metabolic cages. After 6 h, the urine volume and the electrolyte excretion (Na and K) were measured. The role of prostaglandins and nitric oxide was assessed administrating mice with indomethacin and N(ω)-nitro-L-arginine methyl ester (L-NAME), prior the administration of 100 mg/kg SSE. The sedative effects of SSE were analyzed with the pentobarbital-induced sleeping time test. The effects of SSE on motor coordination in mice were evaluated with the rotarod test. The antidepressant-like activity of SSE was analyzed with the forced swimming test (FST) and the tail suspension test (TST). The role of 5-HT2 receptor, α1-and α2-adrenoceptors, or muscarinic receptors was assessed administrating mice with cyproheptadine, prazosin, yohimbine, and atropine, respectively, prior the administration of 100 mg/kg SSE in the FST. The anxiolytic-like activity of SSE (10–100 mg/kg p.o.) was assessed using the light-dark test (LDB), the elevated plus maze test (EPM), the cylinder exploratory test, and the open field test (OFT). The anticonvulsant effect of SSE (1–100 mg/kg) was evaluated in mice administered with different convulsant agents: strychnine, pentylenetetrazol (PTZ), isoniazid (INH) or yohimbine. ResultsThe main compound found in SSE was D-pinitol (42.2%). SSE (100 mg/kg) increased the urinary volume (2.67-fold), as well as the excretion of Na (5.60-fold) and K (7.2-fold). The co-administration of SSE with L-NAME or indomethacin reverted the diuretic activity shown by SSE alone. SSE lacked sedative effects and did not affect motor coordination in mice. SSE (100 mg/kg) showed higher and similar antidepressant-like effect, compared to 20 mg/kg fluoxetine, in the FST and TST, respectively. The co-administration of SSE with yohimbine reverted the antidepressant-like activity shown by SSE alone. SSE (100 mg/kg) showed anxiolytic-like activity in the four models of anxiety, with similar activity with 1.5 mg/kg clonazepam. The seizure-protective effect of SSE was ED50 = 73.9 ± 8.4 mg/kg (INH) and 40.4 ± 5.2 mg/kg (yohimbine). ConclusionThe diuretic effects of SSE involve the possible contribution of prostaglandins and nitric oxide. SSE showed moderate anxiolytic and anticonvulsant effects, whereas the participation of α2-adrenoceptors is probably associated in the antidepressant-like effects of SSE.

Anticalcifying effect of Daucus carota in experimental urolithiasis in Wistar rats

BackgroundUrolithiasis is a burgeoning disease that results from pathological biomineralization. Daucus carota L. is a widely consumed food crop with reported nephroprotective and diuretic activity. Its potential for Ashmari bhedan (destruction of stone/calculi) or treatment of urinary calculi has been explored traditionally. However, no scientific evidence is available to prove its antiurolithiatic efficacy. Moreover, establishing the antiurolithiatic effects of D. carota, an extensively consumed commodity with numerous health benefits, would provide a beneficial dietary measure for the prevention and cure of urolithiasis. ObjectiveThe study aimed at investigating in vivo antiurolithiatic potential of hydroethanolic extract of D. carota roots against calcium oxalate urolithiasis. Materials and methodsEthylene glycol and ammonium chloride induced hyperoxaluria model of urolithiasis in male Wistar rats was used for the study. Urine and serum parameters and, kidney histopathology was used to determine the antilithic efficacy of D. carota root extract. ResultsD. carota extract significantly ameliorated abnormal urinary levels of calcium, oxalate, phosphate, magnesium, citrate, protein and uric acid in lithogenic rats. Serum BUN, creatinine and uric acid levels; and calcium, phosphate and oxalate deposition in kidney tissue were also rendered normal following D. carota treatment. D. carota extract also prevented oxidative stress mediated renal tissue degeneration both prophylactically and curatively. ConclusionThis study suggests antiurolithiatic effect of D. carota roots, which can be attributed to its anticrystallization property, ability to ameliorate urine and serum biochemistry and renal cellularity.

Role of endocannabinoid system in pressure natriuresis, in mice with and without fatty acid amide hydrolase

Kidney is the major organ responsible for long term regulation of blood pressure. Impaired renal sodium excretion and perfusion pressure is main driver of hypertension. This perfusion pressure and renal sodium excretion is called as acute pressure natriuresis (PN). It was surprising to know that none of the study explained the role of endocannabinoids (ECs) in PN and importance of EC hydrolyzing enzymes in the modulation of PN mechanism. This study set out with the primary objective that after acute increase in mean arterial pressure (MAP) either anandamide (AEA) or 2‐arachidonoyl glycerol (2‐AG) is released in the kidney which modulate PN by lowering MAP, natriuretic and diuretic activities. Secondly, effect of genetic and pharmacological ablation of fatty acid amide hydrolase (FAAH) genes in mice modulate the PN relationship. Mice were anesthetized and cannulation was done in trachea, jugular vein, carotid artery and bladder. PN model was established in animals by ligations of celiac and superior mesenteric arteries (CML) and abdominal aorta (AL) while MAP and UV were observed at 10 minutes intervals in FAAH wild type and its knock out littermate. Ligation of celiac and mesenteric arteries resulted in increase in MAP (from baseline to CML‐1 phase) 91 to 121 (mmHg) with corresponding increase in UV from 9 to 17 (ul/min/g kwt) and urinary sodium (UNa) from 1.3 to 3.0 (umol/min/g kwt). MAP and UV reported at CML‐2 ligation was 113 mmHg and 17 ul/min/g kwt. MAP at AL‐1 and AL‐2 was noted as 119 and 104 (mmHg) with corresponding increase in UV 21 and 26 (ul/min/g kwt) while UNa was noted as 3.4 umol/min/g kwt. Pretreatment with selective FAAH inhibitor in the medulla of the kidney resulted in increase in MAP from baseline 88 to 131 and 109 mmHg at CML‐1, CML‐2 respectively while MAP was also observed 119 and 123 mmHg at AL‐1 and AL‐2 phase. There was significant increase (p&lt;0.05) in UV after pretreatment with FAAH inhibitor which was noted 26 and 28 (ul/min/g kwt) at CML‐1 and CML‐2 while 49 and 48 (ul/min/g kwt) at AL‐1 and AL‐2 respectively. FAAH KO animals shifted MAP and UV curves of PN study towards right when compared to FAAH WT group. Analytical data showed significant increase (P&lt;0.05) in 2‐AG levels in the kidney and plasma samples of FAAH WT animals underwent through PN when compared to control FAAH WT while AEA levels was significantly higher (p&lt;0.05) in the kidney of FAAH KO animals with PN as compared to respective control group. It can be concluded that endocannabinoids are released in response to acute increase in MAP and results in diuretic and natriuretic activities which lowers the MAP and keep PN relationship intact. Lastly, regional blocking of FAAH in the kidney shift the MAP and UV curves of the PN models towards left and positively modulate the PN relationship.Support or Funding InformationThis work was supported by National Institute of Diabetes and Digestive and Kidney Disorders grant, DK102539This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors

Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. To overcome these shortcomings, the structure modification of thienoquinoline was carried out in this study, which led to the discovery of novel thienopyridine derivatives as specific urea transporter inhibitors. Further optimization obtained the promising preclinical candidate 8n with not only excellent inhibition effect on urea transporters and diuretic activity on rat model, but also suitable water solubility and Log P value.