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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 Ca 2+ 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., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Tagetes erecta L., known as marigold, belongs to the Asteraceae family and is mainly found in South America. Despite reports that T. erecta flowers are used in folk medicine to treat cardiovascular and renal diseases, there is no study regarding its diuretic effect., Aim: This study aimed to evaluate the chemical composition and the diuretic efficacy of the hydroethanolic extract from T. erecta (HETE) in normotensive (NTR) and hypertensive (SHR) rats., Material and Methods: The HETE was analyzed by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Female and male NTR and SHR received the treatment with vehicle, HETE (0.01 mg/kg, 0.1 mg/kg, and 1 mg/kg) or hydrochlorothiazide (HCTZ; 5 mg/kg) orally. The urinary parameters were measured at the end of the 8-h experiment., Results: From HETE, saccharides and triterpenes were the main annotated compounds, such as erythrodiol and β-amyrin. The urine volume was significantly increased in the groups treated with HETE, in both male and female NTR and SHR rats, compared to the respective vehicle-treated groups. Regarding electrolytes elimination, the treatment with HETE did not reveal significant changes in the urine levels of K + or Cl - , but it showed a natriuretic and Ca 2+ -sparing effects. The HETE beneficial result in reducing Ca 2+ excretion was confirmed through the protective effect found in front of the urinary calcium oxalate precipitation and crystallization. The combination with HCTZ, a classic diuretic and saluretic medicine, significantly enhanced HETE-induced diuresis, natriuresis, and the Ca 2+ -sparing effect. On the other hand, the K + -sparing action was improved in the combination of HETE with amiloride, a standard K + -sparing diuretic. In contrast, the combination of HETE with atropine (a non-selective muscarinic receptor antagonist) and indomethacin (an inhibitor of the cyclooxygenase enzyme), promoted an important reduction in urinary volume, but interestingly the natriuretic effect was maintained., Conclusion: This study contributed to the preclinical validation of the diuretic efficacy of T. erecta, highlighting this species as promising for the development of new pharmacological strategies for the management of kidney disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Our previous study showed that kaempferitrin, the main flavonoid from Bauhinia forficata Link leaves, induces diuresis and saluresis when orally given to rats. Since afzelin (AFZ) and kaempferol (KFL) are active compounds from the biometabolism of kaempferitrin, the diuretic and renal protective properties of these two compounds were evaluated. While the acute treatment with AFZ evoked a diuretic action associated with an increase in Cl - excretion and a Ca 2+ -sparing effect, KFL did not present any activity. The pretreatment with a muscarinic receptor blocker or with an inhibitor of the cyclooxygenase fully avoided AFZ-induced diuresis. AFZ also induced a prolonged (7-day treatment) diuretic effect in normotensive (NTR) and hypertensive rats (SHR), with an increase of urinary Na + and Cl - excretion, while it decreased the elimination of Ca 2+ . AFZ was able to decrease ROS and nitrite generation on kidney homogenates in comparison with the SHR group treated with the vehicle, as well as mitigated the changes in the renal corpuscle region (glomerulus and Bowman's capsule). Moreover, AFZ significantly reduced calcium oxalate crystal formation in urine, with inhibition rates of 41% for the NTR and 92% for the SHR group. Taken together, this study shows that AFZ exerts acute and prolonged diuretic effects plus protective renal properties.

Ethnopharmacological Relevance: Bauhinia forficata Link, commonly known as "cow's paw", is a native plant from South America. Its leaves are widely used in Brazilian folk medicine to treat diabetes and cardiovascular disorders. Although this species' biological potential has been extensively proven as an antidiabetic, anti-inflammatory and antioxidant agent, there is a lack of studies to evidence its action on the cardiovascular system., Aim of the Study: This study was designed to investigate the vascular effects of B. forficata leaves preparations and its majority compound kaempferitrin, as well as its aglycone form kaempferol, in rat aortic rings of normotensive (NTR) and hypertensive (SHR) rats., Materials and Methods: Aorta rings from NTR and SHR precontracted with phenylephrine were exposed to cumulative concentrations of B. forficata extract, fractions (1-50 μg/mL) and compounds (0.001-0.3 μg/mL). The mechanisms involved in the vasorelaxant effect of ethyl-acetate plus butanol fraction (EAButF) were also evaluated., Results: Although kaempferitrin is the most abundant compound found in both methanolic extract and EAButF, 24 minor phenolic compounds were identified in B. forficata leaves, including kaempferol. EAButF was the only with endothelium-dependent and independent vasorelaxant properties in both NTR and SHR. The incubation with L-NAME or ODQ completely blocked EAButF-induced vasorelaxation. On the other hand, the incubation with propranolol, atropine, indomethacin, glibenclamide or barium chloride did not change the vasorelaxant activity of EAButF (50 μg/mL). Nevertheless, the incubation with tetraethylammonium and 4-aminopyridine significantly influenced the EAButF activity. It was also shown that Ca 2+ influx or efflux is not related to EAButF vasorelaxation potential. Kaempferitrin and kaempferol were also able to relax the rat aortic rings in 34.70% and 40.54%, respectively., Conclusions: This study shows, for the first time, the vasorelaxant effect of EAButF from B. forficata leaves, an effect that may be attributed to the modulation of vascular tone through nitric oxide/soluble guanylate cyclase pathway, and potassium channels. The bioactive kaempferitrin and kaempferol seem to be important for the effects observed with the fraction. Finally, preparations obtained from the leaves of B. forficata may be interesting candidates for new or complementary strategies regarding cardiovascular diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)