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Drug Res (Stuttg) 2023; 73(09): 513-519
DOI: 10.1055/a-2182-3665
Original Article

Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats

Viviane Miranda Bispo Steimbach
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Ritade Cássia Vilhena da Silva
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Luísa Nathália Bolda Mariano
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Mariana Zanovello
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Anelise Felício Macarini
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Luisa Mota da Silva
1   Postgraduate Program in Pharmaceutical Sciences, University of Vale do Itajaí (UNIVALI), Itajaí, Brazil
,
Priscila de Souza 
› Author Affiliations Funding Information Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Conselho Nacional de Desenvolvimento Científico e Tecnológico;
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Abstract

Background Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied.

Methods Wistar rats were used and the urine volume was noted for 8 h and further studied.

Results The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate’s precipitation and crystallization.

Conclusions This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.

Key words

Aporphine - diuresis - natriuresis - urolithiasis - calcium oxalate


Publication History

Received: 14 July 2023

Accepted: 26 September 2023

Article published online:
07 November 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Kaufman JS, Dolman L, Rushani D. et al. The contribution of genomic research to explaining racial disparities in cardiovascular disease: a systematic review. Am J Epidemiol 2015; 181: 464-472
    CrossrefPubMedSearch in Google Scholar
  • 2 Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol 2020; 16: 223-237
    CrossrefPubMedSearch in Google Scholar
  • 3 Olsen MH, Angell SY, Asma S. et al. A call to action and a life course strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet 2016; 388: 2665-2712
    CrossrefPubMedSearch in Google Scholar
  • 4 Khalil H, Zeltser R. Antihypertensive Medications. [Updated 2022 May 15]. In: StatPearls [Internet].. Treasure Island (FL): StatPearls Publishing; 2023
    Search in Google Scholar
  • 5 Aggarwal M, Aggarwal B, Rao J. Integrative Medicine for Cardiovascular Disease and Prevention. Med Clin North Am 2017; 101: 895-923
    CrossrefPubMedSearch in Google Scholar
  • 6 de Souza P, Mariano LNB, Cechinel-Zanchett CC. et al. Promising Medicinal Plants with Diuretic Potential Used in Brazil: State of the Art, Challenges, and Prospects. Planta Med 2021; 87: 24-37
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Mariano LNB, Boeing T, da Silva RCV. et al. Exotic Medicinal Plants Used in Brazil with Diuretic Properties: A Review. Chem Biodivers 2022; 19: e202200258
    CrossrefPubMedSearch in Google Scholar
  • 8 Tenfen A, Mariano LNB, Boeing T. et al. Effects of myricetin-3-O-α-rhamnoside (myricitrin) treatment on urinary parameters of Wistar rats. J Pharm Pharmacol 2019; 71: 1832-1838
    CrossrefPubMedSearch in Google Scholar
  • 9 Bolda Mariano LN, Boeing T, Cechinel-Filho V. et al. The acute diuretic effects with low-doses of natural prenylated xanthones in rats. Eur J Pharmacol 2020; 884: 173432
    CrossrefPubMedSearch in Google Scholar
  • 10 Cechinel-Zanchett CC, Bolda Mariano LN, Boeing T. et al. Diuretic and Renal Protective Effect of Kaempferol 3-O-Alpha-l-rhamnoside (Afzelin) in Normotensive and Hypertensive Rats. J Nat Prod 2020; 83: 1980-1989
    CrossrefPubMedSearch in Google Scholar
  • 11 Mariano LNB, Boeing T, Cechinel Filho V. et al. 1,3,5,6-tetrahydroxyxanthone promotes diuresis, renal protection and antiurolithic properties in normotensive and hypertensive rats. J Pharm Pharmacol 2021; 73: 700-708
    CrossrefPubMedSearch in Google Scholar
  • 12 Pereira CRP, Da Silva YS, Cechinel-Zanchett CC. et al. A rare 6-O-glucoside flavonoid from Citharexylum myrianthum Cham. exhibit diuretic and potassium-sparing effects in rats. J Mol Struct 2021; 1239: 130483
    CrossrefPubMedSearch in Google Scholar
  • 13 de Souza P, da Silva RCV, Mariano LNB. et al. Diuretic and Natriuretic Effects of Hesperidin, a Flavanone Glycoside, in Female and Male Hypertensive Rats. Plants (Basel) 2022; 12: 25
    CrossrefPubMedSearch in Google Scholar
  • 14 de Souza P, da Silva RCV, da Silva LM. et al. Gasparotto Junior A. 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. Evid Based Complement Alternat Med 2022; 2022: 4560607
    CrossrefPubMedSearch in Google Scholar
  • 15 Boeing T, da Silva LM, Mariott M. et al. Diuretic and natriuretic effect of luteolin in normotensive and hypertensive rats: Role of muscarinic acetylcholine receptors. Pharmacol Rep 2017; 69: 1121-1124
    CrossrefPubMedSearch in Google Scholar
  • 16 Zanovello M, Bolda Mariano LN, Cechinel-Zanchett CC. et al. Gasparotto Junior A, de Souza P. Tagetes erecta L. flowers, a medicinal plant traditionally used to promote diuresis, induced diuretic and natriuretic effects in normotensive and hypertensive rats. J Ethnopharmacol 2021; 279: 114393
    CrossrefPubMedSearch in Google Scholar
  • 17 Yasui T, Okada A, Hamamoto S. et al. Pathophysiology-based treatment of urolithiasis. Int J Urol 2017; 24: 32-38
    CrossrefPubMedSearch in Google Scholar
  • 18 Han SG, Oh J, Jeon HJ. et al. Kidney Stones and Risk of Osteoporotic Fracture in Chronic Kidney Disease. Sci Rep 2019; 9: 1929
    CrossrefPubMedSearch in Google Scholar
  • 19 Ellison DH. Clinical Pharmacology in Diuretic Use. Clin J Am Soc Nephrol 2019; 14: 1248-1257
    CrossrefPubMedSearch in Google Scholar
  • 20 Sun Q, Sever P. Amiloride: A review. J Renin Angiotensin Aldosterone Syst 2020; 21: 1470320320975893
    CrossrefPubMedSearch in Google Scholar
  • 21 Boeing T, Mariano LNB, Dos Santos AC. et al. Gastroprotective effect of the alkaloid boldine: Involvement of non-protein sulfhydryl groups, prostanoids and reduction on oxidative stress. Chem Biol Interact 2020; 327: 109166
    CrossrefPubMedSearch in Google Scholar
  • 22 Khan SR, Pearle MS, Robertson WG. et al. Kidney stones. Nat Rev Dis Primers 2016; 2: 16008
    CrossrefPubMedSearch in Google Scholar
  • 23 Corbo J, Wang J. Kidney and Ureteral Stones. Emerg Med Clin North Am 2019; 37: 637-648
    CrossrefPubMedSearch in Google Scholar
  • 24 Ivorra MD, Martinez F, Serrano A. et al. Different mechanism of relaxation induced by aporphine alkaloids in rat uterus. J Pharm Pharmacol 1993; 45: 439-443
    CrossrefPubMedSearch in Google Scholar
  • 25 Adelman JP, Maylie J, Sah P. Small-conductance Ca2+-activated K+channels: form and function. Annu Rev Physiol 2012; 74: 245-269
    CrossrefPubMedSearch in Google Scholar
  • 26 Eltze M, Grebe T, Michel MC. et al. Affinity profile at alpha(1)- and alpha(2)-adrenoceptor subtypes and in vitro cardiovascular actions of (+)-boldine. Eur J Pharmacol 2002; 443: 151-168
    CrossrefPubMedSearch in Google Scholar