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Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.

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Piper amalago L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from P. amalago. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with ß-cyclogermacrene, spathulenol, ß-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy cis-cinnamoyl pyrrolidine, methoxy-methylenedioxy trans-cinnamoyl pyrrolidine, and cyclobutene-2,4-bis-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (n = 5). The cardiorenal assays (n = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (n = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from P. amalago. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats' isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME plus 4-aminopyridine. Therefore, P. amalago leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats' mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K+ channels activation.

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There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury-caused by several factors, including ischemia, toxins, and inflammation-has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. This article is a brief review of phytocompounds with potential nephroprotective effects against acute kidney injury (AKI). The classes of Amazonian plant compounds with significant biological activity most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids, and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although with insufficiently explored potential, mainly in the face of AKI, a clinical condition with high morbidity and mortality.

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SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. Post-hoc publications, meta-analysis, and conference presentations of the eight SGLT2i Cardiovascular Outcomes trials (CVOTS) done in diabetic patients constantly echo that this class of drug decreases mortality, reduces cardiovascular events, and prevents heart failure and kidney disease. This review of medical agencies' SGLT2i analysis (FDA and EMA) helps to understand the reality of SGLT2i results in those trials, avoiding to consider observational and statistically undemonstrated endpoints as validated. They also confirmed the unique diuretic mode of action of SGLT2i, promoting osmotic diuresis, and its potential adverse events secondary to hypovolemia and hematocrit increase. They also support the understanding that the beliefs in SGLT2i morbi-mortality benefits are largely overstated mostly based on undemonstrated endpoints. Finally, it is clear that SGLT2i's antidiabetic action, secondary to its renal mode of action, plateaued after a few months and decreased strongly over time, questioning its long-term goal of maintaining diabetic patients' HbA1c below 7%. Also, this effect in patients with renal impairment is quasi null. We think that this review would be very helpful to every physician treating diabetic patients to better balance belief and reality of SGLT2i prescription effects.

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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.

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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.

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This study investigated the diuretic and antiurolithic effects of the hydroalcoholic extract obtained from Morus nigra L. leaves (HEMN) in female hypertensive rats. The rats were treated orally with vehicle (VEH), hydrochlorothiazide (HCTZ), or HEMN. After 8 h, the urine was analyzed. Besides, the precipitation of calcium oxalate (CaOx) was induced in the urine. The HEMN, at a dose of 0.03 mg/g, increased the volume of urine compared to the VEH-treated group and increased the urinary content of Cl- , without altering the excretion of Na+ and K+ . Besides, HENM reduced the elimination of Ca2+ in the urine. On the other hand, at a dose of 0.1 mg/g, it significantly reduced the volume of urine excreted, thus suggesting an antidiuretic effect dependent on the dose used. Similarly, HEMN at concentrations of 1 and 3 mg/mL reduced CaOx crystals' formation in monohydrate and dihydrate forms. However, with the increase in the concentration of HEMN to 10 mg/mL, a significant increase in the formation of CaOx crystals was found. In conclusion, M. nigra extract has a dose-dependent dual effect on urinary parameters, which may have a diuretic and antiurolithic effect at lower doses or the opposite effect at higher doses.

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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.

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The SARS-CoV2 promotes dysregulation of Renin-Angiotensin-Aldosterone. The result is excessive retention of water, producing a state of noxious hypervolemia. Consequently, in COVID-19 injury lung is pulmonary edema. Our report is a case-control study, retrospective. We included 116 patients with moderate-severe COVID-19 lung injury. A total of 58 patients received standard care (Control group). A total of 58 patients received a standard treatment with a more negative fluid balance (NEGBAL group), consisting of hydric restriction and diuretics. Analyzing the mortality of the population studied, it was observed that the NEGBAL group had lower mortality than the Control group, p = 0.001. Compared with Controls, the NEGBAL group had significantly fewer days of hospital stay (p < 0.001), fewer days of ICU stay (p < 0.001), and fewer days of IMV (p < 0.001). The regressive analysis between PaO2/FiO2BAL and NEGBAL demonstrated correlation (p = 0.04). Compared with Controls, the NEGBAL group showed significant progressive improvement in PaO2/FiO2 (p < 0.001), CT score (p < 0.001). The multivariate model, the vaccination variables, and linear trends resulted in p = 0.671 and quadratic trends p = 0.723, whilst the accumulated fluid balance is p < 0.001. Although the study has limitations, the promising results encourage more research on this different therapeutic approach, since in our research it decreases mortality.

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BACKGROUND: The endogenous purine 8-aminoguanine induces diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, mechanistic details are unknown. METHODS: Here, we further explored in rats 8-aminoguanine's effects on renal excretory function by combining studies using intravenous 8-aminoguanine, intrarenal artery infusions of PNPase substrates (inosine and guanosine), renal microdialysis, mass spectrometry, selective adenosine receptor ligands, adenosine receptor knockout rats, laser doppler blood flow analysis, cultured renal microvascular smooth muscle cells, HEK293 cells expressing A2B receptors and homogeneous time resolved fluorescence assay for adenylyl cyclase activity. RESULTS: Intravenous 8-aminoguanine caused diuresis/natriuresis/glucosuria and increased renal microdialysate levels of inosine and guanosine. Intrarenal inosine, but not guanosine, exerted diuretic/natriuretic/glucosuric effects. In 8-aminoguanine-pretreated rats, intrarenal inosine did not induce additional diuresis/natriuresis/glucosuria. 8-Aminoguanine did not induce diuresis/natriuresis/glucosuria in A2B-receptor knockout rats, yet did so in A1- and A2A-receptor knockout rats. Inosine's effects on renal excretory function were abolished in A2B knockout rats. Intrarenal BAY 60-6583 (A2B agonist) induced diuresis/natriuresis/glucosuria and increased medullary blood flow. 8-Aminoguanine increased medullary blood flow, a response blocked by pharmacological inhibition of A2B, but not A2A, receptors. In HEK293 cells expressing A2B receptors, inosine activated adenylyl cyclase, and this was abolished by MRS 1754 (A2B antagonist). In renal microvascular smooth muscle cells, 8-aminoguanine and forodesine (PNPase inhibitor) increased inosine and 3',5'-cAMP; however, in cells from A2B knockout rats, 8-aminoguanine and forodesine did not augment 3',5'-cAMP yet increased inosine. CONCLUSIONS: 8-Aminoguanine induces diuresis/natriuresis/glucosuria by increasing renal interstitial levels of inosine which, via A2B receptor activation, increases renal excretory function, perhaps in part by increasing medullary blood flow.

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