Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation.

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.

Assessment of the Diuretic Effect of the Leaves of Cucumis Dipsaceus Ehrenb (Cucurbitaceae) in Rats: Using Aqueous and 80% Methanol Extracts.

Background: The diuretic activity of the Cucumis dipsaceus leaf, which is used in indigenous medicine, has been claimed but has not yet undergone scientific evaluation. Objective: The objective of this study was to assess the diuretic activity of the aqueous and 80% methanol extracts derived from the leaves of Cucumis dipsaceus in rats. Methods: For the extraction process, the maceration technique was employed to obtain the aqueous and 80% methanol extracts from the Cucumis dipsaceus leaves. Male rats were then divided randomly into eight groups, with six rats in each group. These groups consisted of a negative control group, a positive control group, and three different groups for each extract at varying doses. The urine output volumes, the concentrations of urinary electrolytes (sodium, potassium, and chloride) and urinary pH, were measured and analysed to compare the results among the different groups. Results: Both the aqueous and 80% methanol extracts of Cucumis dipsaceus leaves demonstrated a significant increase in urinary output at doses of 200mg/kg body weight (p<0.01) and 400mg/kg body weight (p<0.001). When comparing the urinary electrolyte excretion with the negative control group, the groups treated with the 400mg/kg body weight dose of the aqueous extract showed significant differences in the urinary excretion of sodium (p<0.05), chloride (p<0.01), and K+ (p<0.01). Similarly, the urinary excretion of K+ and Cl- also exhibited significant differences at moderate doses (K+: p<0.01, Cl-: p<0.05) and the highest doses (both: p<0.01) of the 80% methanol extract. Furthermore, the highest doses of both the aqueous (p<0.01) and 80% methanol (p<0.01) extracts demonstrated significant differences in saluretic effect. Conclusion: Both crude extracts of C. dipsaceus leaves have significant diuretic activity, providing support for the traditional use of the plant as a diuretic agent.

Effects of Functional Biomaterials on the Attributes of Orally Disintegrating Tablets Loaded with Furosemide Nanoparticles: In Vitro and In Vivo Evaluations.

Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the Biopharmaceutics Classification System. It is practically insoluble in water. This study aimed to optimize and formulate porous orally disintegrating tablets (ODTs) prepared by sublimation and loaded with FUR nanoparticles prepared by using a planetary ball mill. Different functional biomaterials called stabilizers were used to stabilize the nanoparticle formula. Pluronic F-127 was the optimum stabilizer in terms of particle size (354.07 ± 6.44), zeta potential (-25.3 ± 5.65), and dissolution efficiency (56.34%). The impact of the stabilizer concentration was studied as well, and a concentration of 3% showed the smallest particle size (354.07 ± 6.44), best zeta potential value (-25.3 ± 5.65), and percentage of dissolution rate (56.34%). A FUR-loaded nanoparticle formula was successfully prepared. The nanoparticle formula was stabilized by using 3% pluronic F-127, and 3% was chosen for further study of the incorporation into oral disintegration tablets prepared by the sublimation technique. The impact of the matrix sublimating agent and superdisintegrant on the ODTs' attributes (in vitro disintegration, wetting time, and in vitro dissolution efficiency) was studied using 32 full factorial designs. In vivo, the diuretic activity was tested for the optimized FUR ODTs by calculating the Lipschitz value using rats as an animal model. The stability of the ODTs loaded with FUR nanoparticles was assessed under accelerated conditions for 6 months. Finally, the ODT formula loaded with FUR NPs showed a rapid onset of action that was significantly faster than untreated drugs. Nanonization and ODT formulation enhances the dissolution rate and bioavailability of FUR. Many factors can be controlled to achieve optimization results, including the formulation and process parameters.

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 µL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 µL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

Constituents of Chimaphila japonica and Their Diuretic Activity.

Three new phenols (1-3), one new cyclohexanol (4), two known phenols (5-6), and six known flavonoids (7-12) were isolated from the n-butanol of the 75% ethanol extract of all plants of Chimaphila japonica Miq. Among them, compound 5 was named and described in its entirety for the first time, and compounds 9 and 10 were reported in C. japonica for the first time. The structures of all compounds were confirmed using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. Biological results show that compounds 4, 7, and 11 exhibited potent diuretic activity. The modes of interaction between the selected compounds and the target diuretic-related WNK1 kinase were investigated in a preliminary molecular docking study. These results provided insight into the chemodiversity and potential diuretic activities of metabolites in C. japonica.

In Vivo Diuretic Activity and Anti-Hypertensive Potential of Hibiscus sabdariffa Extract by Inhibition of Angiotensin-Converting Enzyme and Hypertension Precursor Enzymes.

Aqueous extracts of calyx from Hibiscus sabdariffa (HS) (roselle) are highly appreciated for their nutritional and therapeutic effects, especially as anti-hypertensive substances. This study aimed to evaluate their anti-hypertensive potential through an in vitro inhibition assay of angiotensin-converting enzyme (ACE) and hypertension precursor enzymes and to assess the in vivo diuretic activity of HS. Results showed that HS extract inhibited enzymes belonging to several classes, such as α-amylase, trypsin, chymotrypsin, xanthine oxidase, lipoxygenase, and angiotensin-converting enzyme. In particular, enzymatic kinetics of ACE indicated a competitive inhibition fashion of HS extract. Furthermore, the extracts showed remarkable diuretic and natriuretic effects at doses of 50 mg/kg/bw, 100 mg/kg/b.w, and 200 mg/kg.b.w. These activities can be explained by the high content of phenolic compounds and essential amino acids. Roselle could be a potential source of nutraceuticals and anti-hypertensive bioactive compounds.

Diuretic activity of Euphorbia serpens extracts in Wistar rats.

Euphorbia serpens has been used in central-west region of Argentina in traditional medicine as diuretic plant. The aim of this present study was to evaluate the diuretic activity of E. serpens in-vivo. We used dried aerial parts, and infusions from these were orally administered to Wistar rats. Its effect was evaluated using furosemide as a positive drug and isotonic salt solution as negative control. Their urine output was quantified at several time intervals. The volume of urine excreted and Na+ increased significantly, being similar to furosemide. Mannitol, was the main component in aqueous extracts of E. serpens, and the acetone extract showed the presence of Δ12- oleanane-type triterpenoids compounds, mainly hederagenin. No toxic effects were observed.

Diuretic activity of Sambucus nigra L. ssp. palmensis (Link) R. Bolli, an endemic Canary Islands species / Actividad diurética de Sambucus nigra L. ssp. palmensis (Link) R. Bolli, una especie endémica de las Islas Canarias

To determine the diuretic activity of Sambucus nigra L. ssp. palmensis (Link) R. Bolli (SP). SP was evaluated in adult female Swiss mice. Urinary excretion volume was measured and the concentration of sodium, potassium, chloride, pH and specific conductance of 3 doses of aqueous extract (35.0, 52.2 and 70.0 mg kg-1) were determined. SP (70.0 mg kg-1) produced a higher urinary excretion (6.41 mL) and diuretic index (15%) than hydrochlorothiazide (HCTZ) (6.27 mL and 12%, respectively). The saluretic index indicates a lower sodium excretion than HCTZ (13%) and inversely proportional to the dose (8% -5%). The same is observed for potassium excretion (0.0172-0.0162 mEq.K+/100 g/6 h), which achieves a lower value than the control group (0.0166 mEq.K+/100 g/6 h), suggesting potassium retention. These results support the use of this plant species as a diuretic in Canarian folk medicine.

Determinar la actividad diurética de Sambucus nigra L. ssp. palmensis (Link) R. Bolli (SP). SP fue evaluada en hembras adultas de ratones Swiss. Se midió el volumen de excreción urinaria y se determinó la concentración de sodio, potasio, cloruro, el pH y la conductividad específica de 3 dosis de extracto acuoso (35,0, 52,2 y 70,0 mg kg-1). SP (70,0 mg kg-1) produjo una excreción urinaria (6,41 mL) e índice diurético (15%) superior a hidroclorotiazida (HCTZ) (6,27 mLy 12%, respectivamente). El índice salurético indica una excreción de sodio inferior a HCTZ (13%) e inversamente proporcional a la dosis (8% -5%). Lo mismo ocurre con la excreción de potasio (0,0172-0,0162 mEq.K+/100 g/6 h) que alcanza un dato inferior al del grupo control (0,0166 mEq.K+/100 g/6 h), lo que sugeriría retención de potasio. Estos resultados apoyan el uso de esta especie vegetal como diurético por la medicina popular canaria.

Semisynthesis, Biological Evaluation and Molecular Docking Studies of Barbatic Acid Derivatives as Novel Diuretic Candidates.

Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a-q') were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 µmol/L in vitro. All target compounds were characterized using 1H NMR, 13C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c, 6b', and 6f', exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity. Molecular docking studies further suggested that 6b' had an optimal binding affinity to WNK1 kinases related to diuresis, while 6j could bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents.

Evaluation of anti-inflammatory, diuretic and oral glucose tolerance activities of phenolic compound-rich fractions of Hammada articulata in Albino Wistar rats.

Hammada articulata is a plant widely used by the locals of the Algerian Sahara for multiple medicinal purposes. However, little was known about its chemical composition and the mechanisms of its bioactivity. For this purpose, the derived extracts [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 80% ethanol extract of its aerial parts, were evaluated for their anti-inflammatory, diuretic, and anti-hyperglycemic activities in vivo. A preliminary phytochemical screening of H. articulata extracts showed the presence of a variety of secondary metabolites. RP-HPLC/DAD was used to analyze some fractions obtained by fractionation of the three derived extracts, by column chromatography and chosen because of the abundance and simplicity of their chemical composition. The fractions obtained from EtOAc and n-BuOH extracts showed a particular richness in phenolic compounds mainly naringenin, quercetin, kaempferol, myricetin, and rutin, which were known for their many interesting biological activities. The three derived extracts from H. articulata were assessed for their anti-inflammatory activity in the carrageenan-induced edema model in rats and their diuretic activity using hydrochlorothiazide (HCTZ) as a diuretic reference. All extracts showed considerable anti-inflammatory activity; the highest was registered in the group treated with the n-BuOH extract. However, for the diuretic activity, only the chloroform extract was active, with a diuretic spectrum similar to that of the standard diuretic HCTZ. The anti-hyperglycemic effect was carried out on the three derived extracts administered orally at a dose of 200 mg/kg, using the glucose tolerance test after gavage with the extracts. The EtOAc and n-BuOH extracts showed significant anti-hyperglycemic activity, improving oral glucose tolerance in normal rats.

Pharmacognostic Study, Diuretic Activity and Acute Oral Toxicity of the Leaves of Xiphidium caeruleum Aubl. Collected in Two Different Phenological Stages.

Xiphidium caeruleum Aubl. is traditionally used in Cuba as an analgesic, anti-inflammatory, antilithiatic and diuretic remedy. Here we studied the pharmacognostic parameters of the leaves of X. caeruleum, the preliminary phytochemical composition, diuretic activity and acute oral toxicity of the aqueous extracts from the leaves of plants collected in the vegetative (VE) and flowering (FE) stages. The morphological characteristics and physicochemical parameters of leaves and extracts were determined. The phytochemical composition was assessed by phytochemical screening, TLC, UV, IR and HPLC/DAD profiles. The diuretic activity was evaluated in Wistar rats and compared to furosemide, hydrochlorothiazide and spironolactone. Epidermal cells, stomata and crystals were observed on the leaf surface. Phenolic compounds were identified as the main metabolites, including phenolic acids (gallic, caffeic, ferulic and cinnamic acids) and flavonoids (catechin, kaempferol-3-O-glucoside and quercetin). VE and FE showed diuretic activity. The activity of VE was similar to furosemide, and the activity of FE resembled spironolactone. No acute oral toxicity was observed. The presence of flavonoids and phenols in VE and FE may explain at least in part the traditional use and provide some insight into the reported ethnomedical use as a diuretic. Because of the differences in polyphenol profiles between VE and FE, further studies should be carried out to standardize the harvesting and extraction conditions in order to use X. caeruleum leaf extract as herbal medicine.

3,3-Disubstituted 3,4-Dihydro-1,2,4-benzotriazines: Chemistry, Biological Activity, and Affinity to Sigma Receptors.

By reducing the 2-nitrophenylhydrazone of cyclohexanone with sodium dithionite, an unexpected yellow compound was obtained instead of the corresponding colorless amino derivative. Many years later, the structure of this compound, namely, cyclohexane-3-spiro-3,4-dihydro-1,2,4-benzotriazine, was demonstrated. From that time, the reduction of 2-nitrophenylhydrazones of different kinds of ketones, followed by air oxidation of the initially formed amino compounds, has represented a general way to synthesize a variety of 3,3-disubstituted 3,4-dihydro-1,2,4-benzotriazines. Many derivatives have been obtained so far by a single research group, and most of them have demonstrated interesting pharmacological activities, mainly antihypertensive, anti-inflammatory, and diuretic effects and other activities with lower diffusion. Moreover, 3,3-disubstituted 3,4-dihydro-1,2,4-benzotriazines represent a novel class of ligands for sigma receptors, with nanomolar affinity to the σ1 subtype. This property might promote the development of agents for cardiovascular, neurodegenerative, and proliferative pathologies. The present commentary, by collecting compounds and biological results obtained so far, intends to celebrate the centennial of the discovery of the first member of this class of compounds and to promote further investigation in the field.

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.

Evaluation of the Diuretic Activity of Aqueous and 80% Methanol Extracts of Croton macrostachyus(Euphorbiaceae) Leaves in Saline-Loaded Rats.

BACKGROUND: Croton macrostachyus (Euphorbiaceae) extract is a folk medicine traditionally used for treating a number of disorders, including edematous conditions. The present study aimed to evaluate the diuretic effects of aqueous and 80% methanol leaf extracts of Croton macrostachyus in saline-loaded rats. METHODS: Rats of either sex were randomly assigned into eight groups of eight animals per group. The animals were treated with vehicle (distilled water), standard (furosemide 10 mg/kg), and three doses (100, 200, and 400 mg/kg) of aqueous and 80% methanol leaf extracts after loading of normal saline (15 mL/kg). Then, urine volume, electrolyte concentration, and pH were measured as parameters of evaluation. Concentrations of urinary Na+ K+, and Cl- were determined and Na+:K+ and Cl-:Na+ + K+ ratios calculated to reveal possible mechanisms. RESULTS: The aqueous extract at 200 mg/kg had produced significant diuresis by hour 3, while the same dose of 80% methanol extract had produced substantial diuresis by the end of hour 4. Both extracts at 400 mg/kg produced significant diuresis from hour 2 to hour 5. In terms of effect on electrolysis, 400 mg/kg aqueous extract produced significant natriuresis, and a kaliuresis effect was observed for both extracts at higher doses and 200 mg/kg aqueous extract. CONCLUSION: The findings collectively indicated that both aqueous and 80% methanol extract showed significant diuretic activity, thereby justifying the plant's traditional use as a diuretic agent.

Diuretic Effect and Metabolomics Analysis of Crude and Salt-Processed Plantaginis Semen.

Plantaginis Semen (PS) is well recognized in traditional Chinese medicine (TCM) and health products. Crude PS (CPS) and salt-processed CPS (SPS) are the two most commonly used decoction pieces of PS, and are included in the 2020 edition of Chinese Pharmacopoeia. Although they all have multiple effects, the mechanisms for treating diseases are different and remain unclear, the processing mechanism of SPS is also indeterminate, which hinders their clinical application to a certain extent. In order to solve these problems and further develop PS in the clinical application. Here, we used saline-loaded model rats for experiments, and utilized an integrated approach consisting of pharmacological methods and metabolomics, which could assess the diuretic impact of CPS and SPS ethanol extracts on saline-loaded rats and elucidate the underlying mechanism. The results showed that CPS and SPS both produced increased urine volume excretion and urine electrolyte excretion, but the levels of aldosterone (ALD) and aquaporin 2 (AQP2) were decreased. And 30 differential metabolites such as linoleic acid, lysoPC(O-18:0), sphingosine-1-phosphate, lysoPC(18:0) were found, mainly involving three metabolic pathways. In conclusion, CPS and SPS both have a diuretic effect, and that of SPS is better. This work investigated the possible diuretic mechanisms of CPS and SPS which may also be the mechanism of PS for anti-hypertension. In addition, a holistic approach provided novel and helpful insights into the underlying processing mechanisms of TCM.

[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.

Lagopsis supina exerts its diuretic effect via inhibition of aquaporin-1, 2 and 3 expression in a rat model of traumatic blood stasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lagopsis supina has been used as a traditional medicinal herb for centuries in China. In folk medicine, it is used for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuretic activities. Modern pharmacological investigation have shown that L. supina have an improvement in blood and lymphatic microcirculation, myocardioprotective, and antioxidative activities. Although the pharmacological research of L. supina was more, there was no report on the diuretic activity. AIM OF THE STUDY: This study was to evaluate the diuretic activity and the underlying mechanism of an ethanol extract of L. supina (LS) in a rat model of traumatic blood stasis (TBS). MATERIALS AND METHODS: There were 30 male Sprague-Dawley rats that were randomly assigned to the control group, TBS group, and LS group (10 animals in each group). LS was administered orally (460 mg/kg) once daily for 7 successive days. The control group and TBS group were given an equal amount of 0.3% sodium carboxymethyl cellulose (CMC-Na). For the efficacy evaluation, the urine output volume, the urinary electrolyte concentrations (Na+, K+, Cl- and Ca2+) and pH value, the levels of angiotensin II (Ang II), atriopeptin (ANP), anti-diuretic hormone (ADH) and aldosterone (ALD), as well as aquaporin (AQP)-1, 2 and 3 protein expressions were detected in a rat model of TBS. The protein expressions of AQP-1, 2 and 3 were detected by quantitative immunohistochemistry (IHC) and Western blot analysis. RESULTS: In the efficacy evaluation, rat models treated with LS showed a significant increase in the total urine output (p < 0.01). The urinary electrolyte and the acid-base disturbances, including the decrease of Na+ and Ca2+ levels and the Na+/K+ value together with the increase in the Cl- level and the pH value, in the urine of the LS group were compared with the TBS group. Moreover, the levels of Ang II, ADH and ALD of rat model were decreased after being treated with LS (p < 0.05 or p < 0.01), while the ANP level was increased (p < 0.05). In addition, the results of the quantitative IHC and the Western blot analysis showed that the expression levels of AQP-1, 2 and 3 proteins decreased significantly compared with those of the TBS group. CONCLUSIONS: This is the first reported notable diuretic effect by LS, which probably was through the suppression of the renin-angiotensin-aldosterone system (RAAS) and the regulation of the signaling pathways of AQP-1, 2 and 3 protein expressions. Based on our results, we conclude that L. supina carries out its diuretic effect mainly by down-regulating the levels of AQP-1, 2 and 3 expressions in TBS rat model. These data also embody the traditional Chinese medicine (TCM) application principle of Huo xue li shui. These findings suggest that LS may warrant further evaluation as a possible agent for the diuretic drug in clinical applications. Further research is underway to elucidate the active compounds responsible for the diuretic activity of LS.

Diuretic activity of ethanolic extract of Panicum repens L. roots and rhizomes.

The diuretic activity of ethanolic extract of Panicum repens was investigated in rats. A single oral dose of 500 mg/kg of P. repens extract were given to rats, after 24 h, urine volume, its sodium and potassium concentrations were estimated. Treatment with P. repens extract caused a significant increase in tested parameters as compared to their corresponding controls, p < 0.05.

Health Benefits of Fennel, Rosemary Volatile Oils and their Nano-Forms in Dyslipidemic Rat Model.

BACKGROUND AND OBJECTIVE: Dyslipidemia is a major health problem that may lead to cardiovascular diseases (CVDs). In the present research, a biological experiment was run on dyslipidemic rats to study the health benefits of the volatile oils (VOs) of fennel and rosemary in its original and nano-form using chitosan as carrier. MATERIALS AND METHODS: Rats were divided into 6 groups; normal control, dyslipidemic control and 4 test groups with dyslipidemia and treated by VOs of fennel and rosemary and their respective nano-forms separately. Glucose tolerance test was carried out after 4 weeks. Parameters reflecting oxidative stress/antioxidant plasma catalase, malondialdehyde (MDA) and blood uric acid, were assessed. Plasma lipid profile and tumor necrosis factor alpha (TNF-α) as inflammatory biomarker were determined. Liver and kidney function were assessed as determinant of the safety of the different VO forms. Twenty four hour urinary volume was measured to assess creatinine clearance and to evaluate the possible diuretic activity of the VOs. RESULTS: Dyslipidemic control rats showed dyslipidemia, increased CVDs risk, liver dysfunction, elevated MDA and TNF-α with marked increase in blood sugar after half an hour of glucose ingestion compared to normal control. Treatment with the four VOs forms improved the majority of the biochemical parameters. CONCLUSION: All treatment showed cardio and hepato- protective effect and safety towards kidney and blood sugar. Oxidative stress and inflammatory biomarkers were significantly improved by the different treatments; both VO forms of fennel were more efficient in ameliorating inflammation.

The Study of the Structure-Diuretic Activity Relationship in a Series of New N-(Arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo-[3,2,1-ij]quinoline-5-carboxamides.

In accordance with the principles of "me-too" technique, the preparative method for obtaining has been proposed, and the synthesis of a large series of new N-(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxamides as structurally close analogs of tricyclic pyrrolo- and pyridoquinoline diuretics has been carried out. All target compounds were obtained with high yields and purity by amidation of ethyl ester of the corresponding 2-methyl-pyrroloquinoline-5-carboxylic acid with arylalkylamines in boiling ethanol. Their structure was confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and polarimetry. Moreover, interpretations of their ¹H and 13C-NMR spectra, their mass spectrometric behavior, as well as peculiarities of the polarimetric studies were discussed. The effect of N-(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxamides on the urinary function of the kidneys was studied in white rats by the standard method of oral administration in the dose of 10 mg/kg compared to hydrochlorothiazide. According to the results of the primary pharmacological screening, the structural and biological regularities that were unexpected, but interesting for further studies were revealed. Among the substances studied, the samples, which by their diuretic effect are not inferior and even superior to both the known hydrochlorothiazide and the lead structure of the pyrroloquinoline group, have been found. On this basis, it can be argued that the introduction of the methyl group made by us in position 2 of pyrrolo[3,2,1-ij]quinoline nucleus can be considered as a successful and promising implementation of the "me-too" cloning of tricyclic 4-hydroxyquinoline-2-one diuretics.