Potent Diuretic Research Articles

AN IN VITRO EVALUATION OF ANTI-UROLITHIASIS POTENTIAL OF SIDDHA FORMULATION SAGALANOI CHOORANAM USING STRUVITE CRYSTAL GROWTH INHIBITION ASSAY

Renal calculus is a rising concern, with a prevalence of 12% across the world and 12% in India, which is around 2 million people affected by Urolithiasis. The rise in the ratio has been correlated to genetic predisposition, working in high temperatures, high caffeine intake, lack of physical activity, and groundwater consumption. Yet the major risk factor is a diet that consists of excess animal proteins, which reduces urinary PH and citrate excretion, leading to the formation of Renal calculi. The main aim of this article is to evaluate the anti-urolithiatic potential of a polyherbal Siddha formulation Sagalanoi chooranam obtained from the classical Siddha text Brahmamuni Karukidai Soothiram 380. From the results, it was concluded that the drug has a high potential as an alternative for the management of renal calculus in Siddha. The ingredients efficiently manage renal calculus due to their potent anti-urolithiasis activity, diuretic and anti-inflammatory activity as cited in modern research articles and by mitigating azhal and Vata humour as mentioned in classical Siddha texts. The effect of Sagalanoi chooranam on struvite crystal growth inhibition assay through a significant reduction in the crystal size further validates the drug's efficiency in managing Renal calculus. In such a scenario, the Siddha drug Sagalanoi chooranam can be used as an individual drug or alongside Biomedicine in the management of Renal calculi.

Intravenous delivery of furosemide using lipid-based versus polymer-based nanocapsules: in vitro and in vivo studies

Objectives Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. Methods Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. Results Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization. Conclusions LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

The Impact of Natriuretic Peptides on Heart Development, Homeostasis, and Disease.

During mammalian heart development, the clustered genes encoding peptide hormones, Natriuretic Peptide A (NPPA; ANP) and B (NPPB; BNP), are transcriptionally co-regulated and co-expressed predominately in the atrial and ventricular trabecular cardiomyocytes. After birth, expression of NPPA and a natural antisense transcript NPPA-AS1 becomes restricted to the atrial cardiomyocytes. Both NPPA and NPPB are induced by cardiac stress and serve as markers for cardiovascular dysfunction or injury. NPPB gene products are extensively used as diagnostic and prognostic biomarkers for various cardiovascular disorders. Membrane-localized guanylyl cyclase receptors on many cell types throughout the body mediate the signaling of the natriuretic peptide ligands through the generation of intracellular cGMP, which interacts with and modulates the activity of cGMP-activated kinase and other enzymes and ion channels. The natriuretic peptide system plays a fundamental role in cardio-renal homeostasis, and its potent diuretic and vasodilatory effects provide compensatory mechanisms in cardiac pathophysiological conditions and heart failure. In addition, both peptides, but also CNP, have important intracardiac actions during heart development and homeostasis independent of the systemic functions. Exploration of the intracardiac functions may provide new leads for the therapeutic utility of natriuretic peptide-mediated signaling in heart diseases and rhythm disorders. Here, we review recent insights into the regulation of expression and intracardiac functions of NPPA and NPPB during heart development, homeostasis, and disease.

Abutilon indicum: Bioactive Compounds and Diverse Therapeutic Applications

: A large variety of secondary metabolites are found in medicinal plants, and the majority are significant in medicine. One of the well-known plant species used to cure a wide range of human illnesses is Abutilon indicum. The plant Abutilon indicum has a wide range of therapeutic uses, and its varied parts have been employed to cure a wide range of ailments. Numerous bioactive substances, such as polyphenols, flavonoids, alkaloids, saponins, tannins, and glycosides are present in the plant. Potent antioxidant, anti-inflammatory, antibacterial, hepatoprotective, hypoglycaemic, analgesic, sedative, and diuretic activities have been demonstrated in these compounds. Additionally, the plant has been shown to have cytoprotective properties and to guard against DNA damage brought on by oxidative stress. Future research is required to pinpoint the specific bioactive chemicals responsible for the pharmacological effects of Abutilon indicum and the molecular mechanisms underlying the plant's therapeutic uses. Overall, Abutilon indicum has demonstrated great therapeutic potential and deserves further study as a possible source of homeopathic treatments for various illnesses. The present study covers a summary of the phytochemical and ethnomedicinal applications of Abutilon Indicum that would further help in exploring the research in natural medicine.

Diuretic effects of Hecogenin and Hecogenin acetate via aldosterone synthase inhibition

Hecogenin (HEC) is a steroidal saponin found in many plant species and serves as a precursor for steroidal drugs. The diuretic effects of HEC and its derivative, hecogenin acetate (HA), remain largely unexplored. The present study aimed to explore the potential diuretic effects of HEC and HA compared to furosemide (FUR) and spironolactone (SPIR). Additionally, the study aimed to explore the underlying mechanism particularly focusing on aldosterone synthase gene expression. Fifty-four Sprague-Dawley rats were allocated into nine groups (Group 1–9). Group 1 (control) received the vehicle, Groups 2 received FUR 10 mg/kg, Group 3, 4, and 5 were given HEC, while Groups 6, 7 and 8 received HA i.p at doses of 5, 10, and 25 mg/kg, respectively. Group 9 received SPIR i.p at the dose of 25 mg/kg. Urine volume, diuretic index and diuretic activity were monitored at 1, 2, 3, 4, 5, 6, and 24 h post-administration. Treatment was given daily for seven days. After that, rats were sacrificed and blood was collected for serum electrolytes determination. Adrenal glands were dissected out for gene expression studies. The results revealed that HEC and HA at the administered doses significantly and dose-dependently increased urine and electrolyte excretion. These results were primarily observed at 25 mg/kg of each compound. Gene expression studies demonstrated a dose-dependent reduction in aldosterone synthase gene expression, suggesting aldosterone synthesis inhibition as a potential mechanism for their diuretic activity. Notably, HA exhibited more pronounced diuretic effects surpassing those of HEC. This enhanced diuretic activity of HA can be attributed to its stronger impact on aldosterone synthase inhibition. These findings offer valuable insights into the diuretic effects of both HEC and HA along with their underlying molecular mechanisms.

Alcoholic Extracts of Eleusine indica as Alternative Diuretic Regimens: A Computational Based Investigation

Diuretics are widely used in current clinical practice to increase urine production and excrete electrolytes, particularly sodium and chloride ions, without affecting the absorption of protein, vitamins, carbohydrates, or amino acids. From the time of mercury chloride and organomercurials in ancient times to now (with sulphonamides, thiazides, and furosemide), a lot has changed in the field of diuretics. However, long-term use of such synthetic diuretic agents in clinical practice produces several adverse effects, such as blurred vision, loss of appetite, stomach upset, carcinomas, headaches, phototoxic impact, weakness., etc., as has been observed from recent investigations. Natural regimens can serve as potential alternatives to using nontoxic diuretic agents. Based on long-term ethnomedicinal and biological activity records, we have explored the diuretic effects of the widely known perennial herb in Pacific Islands regions and a weed in agricultural fields, Eleusine indica (L) Gaertn phytoconstituents, on a computation platform. Therefore, we conducted a bio-assay-guided crude extraction using ethanol, followed by further gas chromatography-mass spectrometry (GC-MS) analyses of the extracted crude extracts. Further selected nine constituents (EI_1 to EI_9) carried out the diuretic potency against three putative target enzymes (ACE, KCNJ1, and SLC12A1) along with three standard drugs (VU590, TSM, and FSM) through molecular docking studies using AutoDock 4.2 software. We also predict physicochemical profiles, or Lipinski Rule of Five profiles, toxicity, and pharmacokinetics using various bioinformatics and cheminformatics tools. Based on the overall investigation, it was revealed that EI_6 [Z, Z-6,28-Heptatriacontadien-2-one] was the most potential, nontoxic, and drug-able candidate. In summary, advanced computational tools play a crucial role in selecting potential preclinical candidates within limited resources to accelerate the current drug discovery process.

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.

DIURETIC ACTIVITY OF MUTRALA KASHAYA IN WISTAR RATS

The concept of "Mutrala" is central to this study, referring to the diuretic property of substances that increase urine production. The study aims to develop an effective polyherbal decoction (Kashaya) to address this issue. Several Ayurvedic texts emphasize Mutrala properties of herbs, indicating their ability to stimulate urination. The study involves an experimental approach to assess the diuretic properties of Kashaya in rats. Acute toxicity testing was carried out to evaluate potential harmful effects of the Kashaya formulation at various doses. The diuretic study aimed to compare the effects of the test drug (mutralakashaya) with a standard diuretic (varunadikashaya) and a control (boiled and cooled water). The rats' urine was collected and analyzed for quality and electrolyte levels to determine the diuretic, natriuretic, and saluretic activities. Mutrala Kashaya displayed statistically significant urine output compared to the other two groups, while maintaining essential electrolyte levels in comparison to other two. The developed Mutrala Kashaya exhibited safe usage and potent diuretic effects.

Acetazolamide as a potent chloride-regaining diuretic: time to re-evaluate its diverse actions.

Acetazolamide as a potent chloride-regaining diuretic: time to re-evaluate its diverse actions.

Examination about clinical efficacy and safety of active use of tolvaptan for decompensated congestive heart failure cases

Abstract Background In Japan, Tolvaptan is approved for use as a potent oral diuretic, mainly for severe congestive heart failure. However, over time since the launch of Tolvaptan, there have been many reports of its usefulness when used earlier in milder cases. Based on this background, in August 2015, our facility introduced a clinical pathway (PATH) for acute care for cases with decompensated congestive heart failure (DCHF), in which immediate use of tolvaptan with conventional diuretics ware stipulated to keep patient’s activity by early diuresis. Purpose In this study, we verified the clinical usefulness and safety of PATH for DCHF that prescribes the active use of tolvaptan. Methods From April 2014 to July 2022, 846 DCHF cases admitted to our hospital for the first time were included. They were divided into two groups, N-group(154 cases before introduction of PATH) and P-group(692 cases introduced PATH and prescribed Tolvaptan as stipulated). We investigated their implementation status of each medical treatment in acute phase and hospitalization period(HP), and compared the difference between the two groups. And in P-group, we investigated the occurrence of adverse event(AE), deterioration of renal function (R-event) and hypernatremia (N-event) that required unplanned discontinuation of tolvaptan use, and we investigated the clinical features about the cases with each adverse event. Results There was almost no difference in the patient background before admission or the patient's condition at admission. In P-group, the performance rate of each acute medical care for DCHF was lower and their performance period was shorter compared in N-group. The performance rate of cardiac rehabilitation was higher and its starting time was earlier in P-group. (Figure 1) As a result, HP was significantly shorter in P-group. AE incidence in P-group were 2.2%(R-event) and 4.8%(N-event). Mean age tended to be higher and cognitive function was lower in both AE cases. Cases with R-event were more likely to have pre-existing renal insufficiency. In N-event cases, their activity level before admission was lower and blood sodium level at admission was higher. Most of the N-event(85%) occurred within 7 days.(Figure 2) Conclusions With the introduction of unique clinical pathway that stipulates the active use of tolvaptan, the acute care of cases with decompensated congestive heart failure had been greatly simplified and streamlined, and the hospitalization period had been shortened. Although it is unlikely that all the results were due to the medicinal effects of Tolvaptan, it was thought that the realization of early mobilization due to its strong diuretic effect was linked to these results. A certain rate of feared adverse events, especially hypernatremia, was found to occur, but the rate appeared to be acceptable. However, in elderly and cognitively impaired cases, special caution seemed to be required for several days after the start of tolvaptan use.Figure 1Figure 2

Role of plant bioactive as diuretics: General considerations and mechanism of diuresis.

Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects. This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity. Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well. Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications.

Phytochemical Screening and Diuretic Activity of selected Palestinian Medicinal plants in Mice using an Aqueous Extract Division of Physiology, Pharmacology and Toxicology

Purpose: Man used various natural materials as a remedy for the treatment of various diseases and recently witnessed a vastly growing and renewed interest in herbal medicine globally. In Palestinian folk medicine, Crataegus aronia, Rosmarinus officinalis known as rosemary and Nigella sativa is used as a diuretic and for treatment of hypertension. This study aimed to assess the preliminary phytochemical properties and the diuretic effect of the aqueous extracts of these plants in mice after its intraperitonial administration.&#x0D; Methods: It is an experimental trial applied on mice (n=8, Male, CD-1, weight range: [25-30 gram]), which are divided into two groups (4 in each). The first group administered with the plant extract (500 mg/kg), and the second with normal saline as negative control group. Then urine output and electrolyte contents were quantified up to 6 hours for the three groups and then compared to the control one.&#x0D; Results: Preliminary phytochemical screening reveals the presence of tannins, alkaloids and flavoniods as major phytoconstituents in aqueous extract. Significant diuresis was noted in those received the aqueous extract of Crataegus aronia (p &lt; 0.05) compared to controls. Moreover, aqueous extract had an acidic pH and a mild increase in the electrolyte excretion (Na, K).On the contrary, the aqueous extracts from the Rosemary and Nigella sativa showed no diuretic activity.&#x0D; Conclusions: Our results revealed that Crataegus aronia aqueous extract has a significant potential diuretic effect. Further studies are needed to evaluate this diuretic effect in the relief of diseases characterized by volume overload.

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.

Sonochemical advanced oxidation process for the degradation of furosemide in water: Effects of sonication’s conditions and scavengers

The intensive consumption of pharmaceuticals and drugs in the last decades has led to their increased concentrations in wastewaters from industrial sources. The present paper deals, for the first time, with the sonochemical degradation and mineralization of furosemide (FSM) in water. FSM is a potent loop diuretic used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. The influence of several operating parameters such as acoustic intensity, ultrasonic frequency, initial FSM concentration, solution’s pH, nature of the dissolved gas (Ar, air and N2) and radical scavengers (2-propanol and tert-butanol) on the oxidation of FSM was assessed. The obtained results showed that the degradation rate of the drug increased significantly with the increase of the acoustic intensity in the range of 0.83 to 4.3 W cm−2 and decreased with the augmentation of the frequency in the range of 585–1140 kHz. It was also found that the initial rate of the sonolytic degradation of FSM increased with the increase of its initial concentration (2, 5, 10, 15 and 20 mg/L). The most significant degradation was achieved in acidic conditions at pH 2, while in terms of saturating gas, the rate of FSM degradation decreased in the order of Ar > air > N2. The FSM degradation experiments with radical scavengers showed that the diuretic molecule degraded mainly at the interfacial region of the bubble by hydroxyl radical attack. Additionally, in terms of acoustic conditions, the sono-degradation of 30.24 µmol L-1 of FSM solution demonstrate an optimal performance at 585 kHz and 4.3 W/cm2, the results indicated that even if the ultrasonic action eliminated the total concentration of FSM within 60 min, a low degree of mineralization was obtained due to the by-products formed during the sono-oxidation process. The ultrasonic process transforms FSM into biodegradable and environmentally friendly organic by-products that could be treated in a subsequent biological treatment. Besides, the efficiency of the sonolytic degradation of FSM in real environmental matrices such as natural mineral water and seawater was demonstrated. Consequently, the sonochemical advanced oxidation process represent a very interesting technique for the treatment of water contaminated with FSM.

Investigation of the Diuretic Potential of Diosmetin, a Flavonoid from Citrus lemon in Sprague-Dawley Rat Model

Diosmetin is a flavonoid present in citrus fruit like lemon. Interestingly, lemon juice has been reported for its diuretic activity. The present study aimed to investigate diosmetin's diuretic activity in Sprague Dawley (SD) rats after acute and prolonged administration of different doses. The volume of urine, Na+ and K+ levels, and pH had been estimated with the help of urine samples collected after 6 hrs of normal saline-loaded rats. In the acute diuretic study, a potent and significant response (p&lt;0.001) was observed at the dose of 50 mg/kg in comparison to 20 and 40 mg/kg. The values of the diuretic index for the test groups (20, 40, and 50 mg/kg) were observed to be 1.11, 1.15, and 1.56, respectively. The value of Lipschitz showed that, at the dose of 50 mg/kg, the diuretic activity of diosmetin was 57% in comparison with furosemide (100%). In prolonged diuretic study, diosmetin (50 mg/kg) caused significant diuresis and natriuresis. The diuretic action of diosmetin was significantly decreased with atropine pretreatment, indicating the involvement of muscarinic receptors, while no significant change was observed in the response of diosmetin with pretreatment of L-NAME and indomethacin, excluding the involvement of endothelium related mediators (NO and PGI2). Moreover, the hematological analysis indicated that diosmetin at 50 mg/kg exhibited mild changes in blood-related parameters. In addition, histopathological examination indicated no significant pathological changes. However, compared to the control, mild inflammation was observed in diosmetin and furosemide-treated rats. We concluded that diosmetin increased the volume of urine and urine electrolytes (Na+ and K+) concentration in a dose-dependent manner in the acute diuretic study, while a significant response was also observed in the prolonged diuretic model. Therefore, diosmetin may be considered a potential diuretic candidate for further studies.

Chemicolome and Metabolome Profiling of Xieriga-4 Decoction, A Traditional Mongolian Medicine, Using the UPLC-QTOF/MS Approach.

Xieriga-4 decoction (XRG-4) is a classic prescription Mongolian medicine that has potent diuretic and anti-inflammatory activities. However, its functional components remain unknown. This study aimed to identify the chemical components in XRG-4 and its metabolome in vivo. An ultra-performance liquid chromatography coupled with a quadrupole time-of-flight tandem mass spectrometry based approach was proposed to systematically profile the chemicolome and metabolome of XRG-4. A total of 106 constituents were identified in XRG-4. Eighty-nine components were identified in biological samples, including 78 in urine (24 prototypes and 54 metabolites), 26 in feces (19 prototypes and 7 metabolites), and 9 in plasma (5 prototypes and 4 metabolites). In other tissues, only a few compounds, including alkaloids and iridoids, were detected. This comprehensive investigation of the chemical and metabolic profiles of XRG-4 provides a scientific foundation for its quality control and administration of clinically-safe medication.

Abstract 11943: MCUF-651: A Novel Natriuretic Peptide Receptor A (NPRA) Small Molecule Positive Allosteric Modulator With Blood Pressure Lowering and Renal Enhancing Properties in Experimental Hypertension

Introduction: Hypertension (HTN) represents one of the greatest burdens in human health and is associated with increased morbidity and mortality. Despite the availability of several antihypertensive drugs, most patients have suboptimal blood pressure (BP) control, thus underscoring the need for new therapeutic drugs. The natriuretic peptide receptor A (NPRA) possesses potent vasodilating, natriuretic and diuretic actions via activation by ANP or BNP and generation of its second messenger, cGMP. Recently, we reported the discovery of a small molecule positive allosteric modulator (PAM) for NPRA, MCUF-651, which enhances the ANP/BNP/NPRA/cGMP pathway (PNAS,2021). To date, the in vivo actions of MCUF-651 remains unknown. Here we tested the hypothesis that MCUF-651 would have BP lowering and renal enhancing properties in experimental HTN. Methods: A single IV bolus of MCUF-651 (10mg/kg; n=4) or vehicle (V; n=5) was injected into anesthetized spontaneous hypertensive rats (SHRs). Plasma and urinary cGMP (PcGMP and UcGMP), mean arterial pressure (MAP) and urinary volume (UV) and sodium (UNa) excretion were assessed at baseline (BL) and over 60-mins post-bolus. Results: In SHRs, PcGMP and UcGMP were significantly elevated with MCUF-651 compared to the vehicle group (ΔPcGMP MCUF-651: 16±5, ΔPcGMP V: -2±3, pmol/mL; P =0.003; ΔUcGMP MCUF-651: 78±29, ΔUcGMP V: 30±8, pmol/min, P =0.01), thus supporting NPRA target engagement. Notably, the elevations in cGMP with MCUF-651 were associated with a significant reduction in MAP at 15-mins post bolus compared to vehicle (ΔMAP MCUF-651: -29±14, ΔMAP V: -6±2 mmHg; P =0.04) and this MAP reduction was sustained over 60 mins. Further, UV and UNa excretion were significantly increased, from BL, with MCUF-651 (BL UV: 6 ± 2, 60 mins post bolus UV: 56± 18 μL/min, P &lt;0.001; BL UNa: 1±0.2, 60 mins post bolus UNa: 8±2 μmol/min, P &lt;0.001). Conclusions: We report for the first time that MCUF-651, a novel NPRA small molecule PAM, engages NPRA, increases cGMP and reduces MAP while enhancing sodium and water excretion in experimental HTN. These findings support the development of MCUF-651 as a potential new therapeutic modality to optimize BP lowering goals and reduce adverse outcomes in human HTN.

Identification of Potential Diuretic and Laxative Drug Candidates from Avicennia officinalis L. Bark through In Vivo Mice Model Studies and In Vitro Gas Chromatography-Mass Spectrometry and Molecular Docking Analysis.

Background Avicennia officinalis is a medicinal plant that has traditionally been used as a diuretic, anti-infective, and antiasthmatic. Our investigation was designed to explore the diuretic and laxative potentials of different fractions of this plant's bark extract as well as the identification of possible drug candidates for the activity. Methods Collected bark was extracted in ethanol and fractionated in different polar and nonpolar solvents, i.e., water, chloroform, ethyl acetate, and n-hexane. Phytoconstituents were identified following the published protocols and gas chromatography-mass spectrometry (GC-MS). In the diuretic test, Na+ and K+ ions were measured using a flame photometer whereas the Cl− ion content was measured by titrimetric method against AgNO3. In the laxative test, feces amount and consistency were also measured. Molecular docking analysis was conducted using the “Vina Wizard” program in PyRx-Python Prescription 0.8. Results Phytochemical analysis indicated that alkaloids, tannins, flavonoids, saponins, glycosides, and terpenoids were detected in the most bioactive crude extracts, whereas alkaloids, terpenoids, saponins, and gums were found in bioactive n-hexane fraction and steroids, glycosides, and terpenoids were found positive in chloroform fraction. Almost all the fractions demonstrated a dose-dependent increment of stool production with a soft consistency; however, the chloroform fraction was found to be the most active (p < 0.001). The crude extract and n-hexane fractions significantly increased (p < 0.01) the urinary output at the dose of 200 and 400 mg/kg. The concentrations of Na+, K+, and Cl− in collected urine were found to be more compared with the control group. The GC-MS analysis identified seven compounds in bioactive n-hexane fraction (phenolic and ester-type mainly) whereas seven other compounds (acidic and ester-type mainly) were identified in chloroform fraction. In molecular docking, two drug candidates of this extract (2,4-bis(2-phenylpropan-2-yl)phenol and 2-[4-[2-(dimethylamino)-2-oxo-1,1-diphenylethyl]phenyl]-2-phenylacetic acid) showed excellent binding affinity with the receptor compared with furosemide. Conclusion A. officinalis bark might be a potential source of bioactive compounds for treating hypertension, edema, and constipation.

Expression of Cytotoxicity, ROS, MMP and Quantitative PCR of Barleria lupulina Lindl. on THP-1 Cells

Barleria lupulina Lindl. (Hop-headed) is a popular medicinal plant that has been used as drug plant since the ancient time. It is a large genus comprising of over 300 species of shrubs, and many of which are known for their ornamental and or medicinal values. The plant is commonly known as Sornomukhi, Hophead Philipine violet, Vishalyakarni, etc. It is native to India and widely distributed in Southern and Western India. The plant is a small shrub, possess potent anti-inflammatory, analgesic, anti-leukemic, antitumor, anti- hyperglycemic, anti-amoebic, virucidal, diuretic, bactericidal and antibiotic properties. Cytotoxicity, bioactive assay and genetic analysis of Barleria lupulina Lindl. were investigated in the present communication. The leaf extract of B. lupulina were investigated by MTT, NRU, DNA fragment, reactive oxygen species generation, mitochondrial membrane potential assay, gene expression analysis and cDNA synthesis to evaluate anti-cancerous potency using cancerous THP-1 cell lines in vitro and in vivo. HPTLC analysis reveals four spots and GC-MS analysis displayed the presence of eleven bioactive compounds among which benzofuranon, hexadecanoic acid, ethyl 9,12,15-octadecatrienoate, and 3,7,11,15-tetramethyl-2-hexadecanoic acid were the most prominent compounds. The ethanolic extract showed significant cytotoxicity (P&lt;0.5) against THP-1 cell line at a concentration of 1mg/ml. The cells were also observed for apoptosis through DNA fragmentation in B. lupulina treated cells. It can be concluded that if the dose range was further refined within the range of 100-1000 μg/ml there could be dose at which the entire population of the THP-1 cell line would be apoptosis induced. The extract induced ROS in the cells after 30 minutes of exposure displaying cytotoxic effects and DNA fragmentation assay. The B. lupulina contain anti-cancerous activity so that it can be used as an alternative drug.

Preclinical Pharmacokinetic Studies of a Novel Diuretic Inhibiting Urea Transporters.

Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na+, K+, Cl−, and other electrolytes. In our previous studies, 25a, a promising diuretic candidate inhibiting UT, was discovered and showed potent diuretic activities in rodents. Here, a sensitive liquid chromatography–tandem mass spectrometry method for the quantitation of 25a in rat plasma, urine, feces, bile, and tissue homogenates was developed and validated to support the preclinical pharmacokinetic studies. The tissue distribution, excretion, and plasma protein binding were investigated in rats. After a single oral dose of 25a at 25, 50, and 100 mg/kg, the drug exposure increased linearly with the dose. The drug accumulation was observed after multiple oral doses compared to a single dose. In the distribution study, 25a exhibited a wide distribution to tissues with high blood perfusion, such as kidney, heart, lung, and spleen, and the lowest distribution in the brain and testis. The accumulative excretion rate of 25a was 0.14%, 3.16%, and 0.018% in urine, feces, and bile, respectively. The plasma protein binding of 25a was approximately 60% in rats and 40% in humans. This is the first study on the preclinical pharmacokinetic profiles of 25a.