The acute diuretic effects with low-doses of natural prenylated xanthones in rats

Mariano, Luísa Nathália Bolda; Boeing, Thaise; Cechinel‐Filho, Valdir; Niero, Rivaldo; Silva, Luísa Mota da; Souza, Priscila de

doi:10.1016/j.ejphar.2020.173432

Cited by 14 publications

(15 citation statements)

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“…This dataset shows that this xanthone probably does not have its diuretic and natriuretic effects related to the nitric oxide (NO) production. However, it is worth mentioning that in our previous study, indomethacin (a cyclooxygenase inhibitor) precluded TDP-induced diuresis [ 18 ], so we can suggest that the mechanisms responsible for the effects of xanthone presented here could involve direct vasodilator actions on the renal vascular bed.…”

Section: Resultsmentioning

confidence: 67%

“…Bolda Mariano et al [ 18 ] described the acute diuretic effect of the xanthone TDP ( Figure 1 ), in which a single oral dose of 0.1 mg/kg was able to induce diuresis and increase of the urinary electrolytes excretion in both normotensive (NTR) and hypertensive (SHR) rats. Herein, to better understand the renal effects of TDP, especially in a dose-repeated treatment, the present study was performed.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we described the diuretic effect of the methanolic extract and fractions obtained of branches from G. achachairu Rusby (Clusiaceae) [ 17 , 18 ], which is a plant native of Bolivia, popularly known as “achachairu” [ 19 ]. Phytochemical study permitted to isolate the 1, 5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano (2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP), which showed a significant diuretic effect in rats after a single-dose treatment [ 17 , 18 ]. Xanthones are polyphenolic compounds, and their structures are recognized for their importance in discovering new active compounds [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

Mariano

Boeing

Filho

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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The previous study showed that 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na+, K+, Cl−, and Ca2+). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-β-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.

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Section: Resultsmentioning

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

Mariano

Boeing

Filho

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Nothofagin, a mono-C-glycoside of 4,2′,4′,6′-tetrahydroxy-dihydrochalcone found in Leandra dasytricha leaves, demonstrated the ability to induce diuresis [ 23 ], renoprotection [ 24 ], vasodilation [ 12 ], and hypotensive effect [ 25 ]. Different compounds from the xanthone classes isolated from Garcinia achachairu branches revealed acute diuretic actions [ 26 , 27 ], prolonged diuretic and renoprotective effects [ 28 ], and antiurolithic properties [ 29 ]. Besides, glycosylated flavonoids obtained from the leaves of Bauhinia forficata revealed vasodilator [ 30 ], diuretic, and kidney protective effects [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Boldine, an Alkaloid from Peumus boldus Molina, Induces Endothelium-Dependent Vasodilation in the Perfused Rat Kidney: Involvement of Nitric Oxide and Small-Conductance Ca2+-Activated K+ Channel

Souza

Silva

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Boldine, 2,9-dihydroxy-1,10-dimethoxyaporphine, is the main alkaloid found in the leaves and bark of Peumus boldus Molina. In recent years, boldine has demonstrated several pharmacological properties that benefit endothelial function, blood pressure control, and reduce damage in kidney diseases. However, the renal vasodilator effects and mechanisms remain unknown. Herein, perfused rat kidneys were used to study the ability of boldine to induce vasodilation of renal arteries. For that, left kidney preparations with and without functional endothelium were contracted with phenylephrine and received 10–300 nmol boldine injections. The preparations were then perfused for 15 min with phenylephrine plus L-NAME, indomethacin, KCl, tetraethylammonium, glibenclamide, apamin, charybdotoxin, or iberiotoxin. In 30, 100, and 300 nmol doses, boldine induced a dose-and endothelium-dependent relaxing effect on the renal vascular bed. No vasodilator effects were observed in preparations lacking functional endothelium. While the inhibition of the cyclooxygenase enzyme through the addition of indomethacin did not cause any change in the vasodilating action of boldine, the nonselective nitric oxide synthase inhibitor L-NAME fully precluded the vasodilatory action of boldine at all doses tested. The perfusion with KCl or tetraethylammonium (nonselective K+ channels blocker) also abolished the vasodilatory effect of boldine, indicating the participation of K+ channels in the renal action of boldine. The perfusion with glibenclamide (selective ATP-sensitive K+ channels blocker), iberiotoxin (selective high-conductance Ca2+-activated K+ channel blocker), and charybdotoxin (selective high- and intermediate-conductance Ca2+-activated K+ channel blocker) did not modify the vasodilatory action of boldine. On the other hand, the perfusion with apamin (selective small-conductance Ca2+-activated K+ channel blocker) completely prevented the vasodilatory action of boldine at all doses tested. Together, the present study showed the renal vasodilatory properties of boldine, an effect dependent on the generation of nitric oxide and the opening of a small-conductance Ca2+-activated K+ channel.

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“…В зв'язку з цим важливим завданням експериментальної фармакології є створення нових ефективних препаратів для поліпшення діяльності нирок та збільшення сечовиділення при патологічних станах ( Barja-Fidalgo et al, 1999;Bolda et al, 2019;Bolda et al, 2020).…”

Section: вступunclassified

Acute toxicity and diuretic activity of amino-3-methylxanthine derivates

Korniyenko¹,

Ladohubets²,

Harkusha³

et al. 2021

VSTFH

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A vital problem of the contemporary pharmacology lies in creation of safer and more efficient medicinal products. Regulation of sodium balance and water being one of the important homeostatic functions is essential for developing the methods of rational therapy through means of diuretics of renal function of kidneys.This work is aimed to study the dependence of acute toxicity and diuretic activity on chemical structure of the newly synthesized 7-substituted-8-amino-3-methylxanthines in experiments on rats.The acute toxicity of 7-(2-hydroxy-3-p-methoxyphenoxy) propyl-8-substituted theophylline has been studied on the intact white nonlinear mice weighing 20-24 LD50 and has been calculated according to the method of Körber. The study of the diuretic activity of the above-mentioned compounds has been carried out on white rats of Wistar line weighing 180-195g according to the method of Y.B. Berkhina.The gained outcome of research into the acute toxicity of 7-substituted-8-amino-3methylxanthines (compounds 1-11) has shown that LD50 of the synthesized compounds is in the range from 290 to 835 mg/kg. The most toxic (LD50=290 mg/kg) compound is the 6 th one: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-n-butylaminoethyl. Substitution in the 8 th position of the molecule of 7-substituted-8-amino-3-methylxanthines n-butylamine (compound 6) of radical with 4-benzylpiperazine-1-ilne (compound 11), p-ethoxyphenylamic (compound 10) N,N-diethylaminoethylamine (compound 4), 4-methylpiperazine-1-ilne (compound 1), N,N-diethylaminoethylamine (compound 3), N-methyl-N-benzylamine (compound 2), (pyrrolidine-1-ilne (compound 7), m-tolylamine (compound 9), βhydroxyethylepiperazine-1-ilne (compound 8), (furil-2)methylamine (compound 5) causes a reduction of the acute toxicity of the aforesaid substances.Analysis of the diuretic activity research shows that derivatives of 7-substituted-8amino-3-methylxanthines (compounds 1-11) increases excretion of urine in the range from 25.1% to 201.4% (p<0.05).The most signifying diuretic activity has been shown by the compound 5: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-(furil-2)methylaminoxanthine, which in the dose of 41.8 mg/kg enhances the water diuresis for 201. 4% (p<0.01).Introduction to the 8 th position of the molecule of 7-substituted-8-amino-3metylxanthines instead of furil-2-methylamine (compound 5) radical of m-tolylamine (compound 9), n-butylamine (compound 6) and p-ethoxyphenylamine (compound 10) fragments leads to a reduction in renal excretory function for 143.5%; 131.8% and 111%, accordingly. Hydrochlorothiazide in the dose of 25 mg/kg enhances the water diuresis for 90.1%.Thus, the most signifying diuretic effect is observed in the compound 5, which exceeds the effect of the hydrochlorothiazide for 111.3% (p<0.05) and has been selected for further study of the specific activity.

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The acute diuretic effects with low-doses of natural prenylated xanthones in rats

Cited by 14 publications

References 41 publications

Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

Boldine, an Alkaloid from Peumus boldus Molina, Induces Endothelium-Dependent Vasodilation in the Perfused Rat Kidney: Involvement of Nitric Oxide and Small-Conductance Ca2+-Activated K+ Channel

Acute toxicity and diuretic activity of amino-3-methylxanthine derivates

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