Skip to main content
SpringerLink
Log in

Diuretic effect of extracts, fractions and two compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone from Rubus rosaefolius Sm. (Rosaceae) leaves in rats

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of Rubus rosaefolius Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na+ and K+ excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E2 levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from R. rosaefolius leaves in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ali SA, Zaitone SA, Moustafa YM (2015) Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich’s carcinoma. Can J Physiol Pharmacol 93:695–708

    Article  CAS  PubMed  Google Scholar 

  • Aston R (1959) A rat diuretic screening procedure. Toxicol Appl Pharm 1:277–282

    Article  CAS  Google Scholar 

  • Bagattoli PC, Cipriani DC, Mariano LN, Correa M, Wagner TM, Noldin VF, Filho VC, Niero R (2016) Phytochemical, antioxidant and anticancer activities of extracts of seven fruits found in the southern Brazilian Flora. Indian J Pharm Sci 78:34–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benjumea D, Abdala S, Hernandez-Luis F, Pérez-Paz P, Martin-Herrera D (2005) Diuretic activity of Artemisia thuscula, an endemic canary species. J Ethnopharmacol 100:205–209

    Article  CAS  PubMed  Google Scholar 

  • Bhasin B, Velez JC (2016) Evaluation of polyuria: the roles of solute loading and water diuresis. Am J Kidney Dis 3:507–511

    Article  Google Scholar 

  • Blowey DL (2016) Diuretics in the treatment of hypertension. Pediatr Nephrol. doi:10.1007/s00467-016-3334-4

    PubMed  Google Scholar 

  • Bunbupha S, Prachaney P, Kukongviriyapan U, Kukongviriyapan V, Welbat JU, Pakdeechote P (2015) Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension. Clin Exp Pharmacol Physiol 42:1189–1197

    Article  CAS  PubMed  Google Scholar 

  • Costa VP, Mayworm MAS (2011) Plantas medicinais utilizadas pela comunidade do bairro dos Tenentes - município de Extrema. MG Rev Bras Pl Med 13:282–292

    Article  Google Scholar 

  • Da Silva RC, De Souza P, Crestani S, Gasparotto Júnior A, Boligon AA, Athayde ML, Da Silva-Santos JE (2015) Hypotensive and diuretic effect of the butanolic soluble fraction of the hydroethanolic extract of bark of Scutia buxifolia Reissek in rats. J Ethnopharmacol 172:395–401

    Article  Google Scholar 

  • De Souza P, Crestani S, Da Silva RC, Gasparotto F, Kassuya CA, Da Silva-Santos JE, Gasparotto Júnior A (2013) Involvement of bradykinin and prostaglandins in the diuretic effects of Achillea millefolium L. (Asteraceae). J Ethnopharmacol 26:157–161

    Article  Google Scholar 

  • Dormans TP, van Meyel JJ, Gerlag PG, Tan Y, Russel FG, Smits P (1996) Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. J Am Coll Cardiol 28:376–382

    Article  CAS  PubMed  Google Scholar 

  • Ellison DH, Loffing J (2009) Thiazide effects and adverse effects: insights from molecular genetics. Hypertension 54:196–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Estrada O, Contreras W, Acha G, Lucena E, Venturini W, Cardozo A, Alvarado-Castillo C (2014) Chemical constituents from Licania cruegeriana and their cardiovascular and antiplatelet effects. Molecules 19:21215–21225

    Article  PubMed  Google Scholar 

  • Fan Z, Zhou L, Xiong T, Zhou J, Li Q, Tan Q, Zhao Z, Jin J (2015) Antiplatelet aggregation triterpene saponins from the barks of Ilex rotunda. Fitoterapia 101:19–26

    Article  CAS  PubMed  Google Scholar 

  • Ferreira LL, Gomes MV, Paes BM, Do Carmo PL, Konno TU, Esteves FA, Lopes NP, Tomaz JC, Leal IC, Guimarães DO, Muzitano MF, Raimundo JM (2016) The Hydroalcoholic extract of leaves of Mandevilla moricandiana induces NO-mediated vascular relaxation. Planta Med. doi:10.1055/s-0042-108203

    Google Scholar 

  • Gasparotto A Jr, Boffo MA, Lourenço ELB, Stefanello MEA, Kassuya CAL, Marques MCA (2009) Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats. J Ethnopharmacol 122:517–522

    Article  PubMed  Google Scholar 

  • Gasparotto A Jr, Prando TBL, Leme TSV, Gasparotto FM, Lourenço ELB, Rattmann YD, Silva-Santos JE, Kassuya CAL, Marques MCA (2012) Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin. J Ethnopharmacol 141:501–509

    Article  PubMed  Google Scholar 

  • Grandi TSM, Trindade JA, Pinto MJF, Ferreira LL, Catella AC (1989) Acta boto bras. 3(2): supl. Plantas Medicinais de Minas Gerais, Brasil

  • Gupta S, Neyses L (2005) Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J 26:644–649

    Article  CAS  PubMed  Google Scholar 

  • Horie T, Ohtsuru Y, Shibata K, Yamashita K, Tsukayama M, Kawamura Y (1998) 13CNMR spectral assignment of the A-ring of polyoxygenated flavones. Phytochemistry 47:865–874

    Article  CAS  Google Scholar 

  • Hung YC, Yang HT, Yin MC (2015) Asiatic acid and maslinic acid protected heart via anti-glycative and anti-coagulatory activities in diabetic mice. Food Funct 6:2967–2974

    Article  CAS  PubMed  Google Scholar 

  • Jeong HS, Hong SJ, Cho JY, Lee TB, Kwon JW, Joo HJ, Park JH, CW Y, Lim DS (2016) Effects of Rubus occidentalis extract on blood pressure in patients with prehypertension: randomized, double-blinded, placebo-controlled clinical trial. Nutrition 32:461–467

    Article  PubMed  Google Scholar 

  • Joly AB (1991) Botânica: Introdução à taxonomia vegetal. Companhia Editora Nacional, SP, Brazil, p. 777

    Google Scholar 

  • Jorge LIF, Markman BEO (1993) Caracterização histológica das folhas e dos frutos de Rubus rosaefolius Smith (amora-domato). Rev Inst Adolfo Lutz 53:1–4

    Google Scholar 

  • Kane MO, Sene M, Anselm E, Dal S, Schini-Kerth VB, Augier C (2015) Role of AMP-activated protein kinase in NO- and EDHF-mediated endothelium-dependent relaxations to red wine polyphenols. Indian J Physiol Pharmacol 59(4):369–379

    PubMed  Google Scholar 

  • Kanegusuku M, Sbors D, Bastos ES, de Souza MM, Cechinel-Filho V, Yunes RA, Delle Monache F, Niero R (2007) Phytochemical and analgesic activity of extract, fractions and a 19-hydroxyursane-type triterpenoid obtained from Rubus rosaefolius (Rosaceae). Biol Pharm Bull 30:999–1002

    Article  CAS  PubMed  Google Scholar 

  • Kaplan NM, Carnegie A, Raskin P (1985) Potassium supplementation in hypertensive patients with diuretic-induced hypokalemia. N Engl J Med 312:746–749

    Article  CAS  PubMed  Google Scholar 

  • Kau ST, Keddie JR, Andrews D (1984) A method for screening diuretic agents in the rat. J Pharmacol Methods 11:67–75

    Article  CAS  PubMed  Google Scholar 

  • Kaur S, Muthuraman A (2016) Therapeutic evaluation of rutin in two-kidney one-clip model of renovascular hypertension in rat. Life Sci 150:89–94

    Article  CAS  PubMed  Google Scholar 

  • Kazama CC, Uchida DT, Canzi KN, De Souza P, Crestani S, Gasparotto Junior A, Laverde Junior A (2012) Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia haw. (Cactaceae). J Ethnopharmacol 144:86–93

    Article  CAS  PubMed  Google Scholar 

  • Kim JA, Sheen MR, Lee SD, Jung JY, Kwon HM (2009) Hypertonicity stimulates PGE2 signaling in the renal medulla by promoting EP3 and EP4 receptor expression. Kidney Int 75:278–284

    Article  CAS  PubMed  Google Scholar 

  • Kukongviriyapan U, Kukongviriyapan V, Pannangpetch P, Donpunha W, Sripui J, Sae-Eaw A, Boonla O (2015) Mamao pomace extract alleviates hypertension and oxidative stress in nitric oxide deficient rats. Nutrients 7(8):6179–6194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar BN, Swamy BM, Swamy A, Murali A (2010) A review of natural diuretics. Res J Pharm Biol Chem Sci 1:615–634

    Google Scholar 

  • Legroux-Gerot I, Catanzariti L, Marchandise X, Duquesnoy B, Cortet B (2004) Bone mineral density changes in hypercalciuretic osteoporotic men treated with thiazide diuretics. Joint Bone Spine 71:51–55

    Article  PubMed  Google Scholar 

  • Leme TS, Prando TB, Gasparotto FM, De Souza P, Crestani S, De Souza LM, Cipriani TR, Lourenço EL, Gasparotto Junior A (2013) Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus Ilicifolia Mart ex Reissek (Celastraceae). J Ethnopharmacol 150:154–161

    Article  Google Scholar 

  • Li J, LF D, He Y, Yang L, Li YY, Wang YF, Chai X, Zhu Y, Gao XM (2015) Chemical constituents and biological activities of plants from the genus Rubus. Chem Biodivers 12:1809–1847

    Article  CAS  PubMed  Google Scholar 

  • Lim YC, Budin SB, Othman F, Latip J, Zainalabidin S (2016) Roselle polyphenols exert potent negative inotropic effects via modulation of intracellular calcium regulatory channels in isolated rat heart. Cardiovasc Toxicol. doi:10.1007/s12012-016-9379-6

    PubMed  Google Scholar 

  • Lorenzi H, Bacher L, Lacerda M, Sartori S (2006) Frutas brasileiras e exóticas cultivadas (de consumo in natura). Instituto Plantarum de Estudos da Flora, São Paulo

    Google Scholar 

  • Madlala HP, Van Heerden FR, Mubagwa K, Musabayane CT (2015) Changes in renal function and oxidative status associated with the hypotensive effects of Oleanolic acid and related synthetic derivatives in experimental animals. PLoS One 10(6):e0128192

    Article  PubMed  PubMed Central  Google Scholar 

  • Madlala HP, Metzinger T, van Heerden FR, Musabayane CT, Mubagwa K, Dessy C (2016) Vascular endothelium-dependent and independent actions of Oleanolic acid and its synthetic Oleanane derivatives as possible mechanisms for hypotensive effects. PLoS One 11(1):e0147395

    Article  PubMed  PubMed Central  Google Scholar 

  • Mauro C et al (2002) Estudo botânico, fitoquímico e avaliação da atividade antimicrobiana de Rubus rosaefolius Sm. –Rosaceae. Rev Bras Farmacogn 12:23–25

    Article  Google Scholar 

  • Niero R, Cechinel-Filho V (2008) Therapeutic potential and chemical composition of plants from the genus Rubus: a mini review of the last 10 Years. Nat Prod Commun 3:437–444

    CAS  Google Scholar 

  • Ostrosky EA, Marcondes EM, Nishikawa SO, Lopes PS, Varca GH, Pinto TJ, Consiglieri TV, Baby AR, Velasco MV, Kaneko TM (2011) Rubus rosaefolius Extract as a natural preservative candidate in topical formulations. AAPS PharmSciTech 12:732–737

    Article  PubMed  PubMed Central  Google Scholar 

  • Petreanu M, Ferreira EK, Sagaz AP, Vendramini-Costa DB, Ruiz AL, De Carvalho JE, Campos A, Cechinel Filho V, Delle Monache F, Niero R (2015) Uncommon Trimethoxylated Flavonol Obtained from Rubus rosaefolius Leaves and Its Antiproliferative Activity. Evid. Based Complement. Alternat. Med. 341216

  • Prando TB, Barboza LN, Araújo VO, Gasparotto FM, de Souza LM, Lourenço EL, Gasparotto Junior A (2015) Involvement of bradykinin B2 and muscarinic receptors in the prolonged diuretic and antihypertensive properties of Echinodorus Grandiflorus (Cham. & Schltdl.) Micheli. Phytomedicine. doi:10.1016/j.phymed.2015.10.020

    PubMed  Google Scholar 

  • Ribeiro RA, de Barros F, de Melo MM, Gomes C, Trolin G (1986) Acute antihypertensive effect in conscious rats produced by some medicinal plants used in the state of São Paulo. J Ethnopharmacol 15:261–269

    Article  Google Scholar 

  • Ribeiro RA, de Barros F, de Melo MM, Muniz C, Chieia S, Wanderley MG, Gomes C, Trolin G (1988) Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of São Paulo, Brasil. J Ethnopharmacol 24:19–29

    Article  Google Scholar 

  • Rodriguez-Rodriguez R (2015) Oleanolic acid and related triterpenoids from olives on vascular function: molecular mechanisms and therapeutic perspectives. Curr Med Chem 22:1414–1425

    Article  CAS  PubMed  Google Scholar 

  • Sica DA, Carter B, Cushman W, Hamm L (2011) Thiazide and loop diuretics. J Clin Hypertens (Greenwich) 13:639–643

    Article  CAS  Google Scholar 

  • Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J (2015) Bioactive compounds and antioxidant activity in different types of berries. Int J Mol Sci 16:24673–24706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stichtenoth DO, Frolich JC (2000) COX-2 and the kidneys. Curr Pharm Des 6:1737–1753

    Article  CAS  PubMed  Google Scholar 

  • Vanamala U, Elumalai A, Eswaraiah MC, Shaik A (2012) An updated review on diuretic plants. Int J Pharm Biol Arch 3:29–31

    Google Scholar 

  • Weisheng F, Qian L, Xiaoke Z, Haixue K (2006) Chemical constituents from Lysionotus Pauciflora. Tianran Chanwu Yanjiu Yu Kaifa 18:617–620

    Google Scholar 

  • Wright CI, Van-Buren L, Kroner CI, Koning MMG (2007) Review herbal medicines as diuretics: a review of the scientific evidence. J Ethnopharmacol 114:1–31

    Article  CAS  PubMed  Google Scholar 

  • Yang F, Suo Y, Chen D, Tong L (2016) Protection against vascular endothelial dysfunction by polyphenols in sea buckthorn berries in rats with hyperlipidemia. Biosci Trends 10(3):188–196

    Article  PubMed  Google Scholar 

  • Zeng B, Liu GD, Zhang BB, Wang SS, Ma R, Zhong BS, He BQ, Liang Y, FH W (2016) A new triterpenoid saponin from Clinopodium Chinense (Benth.) O. Kuntze. Nat Prod Res 30:1001–1008

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Zhang Z, Yang Y, Zu X, Guan D, Guan Y (2011) Diuretic activity of Rubus idaeus L (Rosaceae) in rats. Trop J Pharm Res 10:243–248

    Article  Google Scholar 

Download references

Acknowledgments

Thanks to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) and Universidade do Vale do Itajaí (UNIVALI) for their financial support. PS is grateful for the Post-Doctoral scholarship and financial support from PNPD/CAPES.

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Itajaí, SC, 88302-901, Brazil

    Priscila de Souza, Thaise Boeing, Lincon Bordignon Somensi, Camile Cecconi Cechinel-Zanchett, Marcel Petreanu, Rivaldo Niero, Valdir Cechinel-Filho, Luisa Mota da Silva & Sérgio Faloni de Andrade

  2. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, 14040-903, Brazil

    Jairo Kenupp Bastos

Authors
  1. Priscila de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thaise Boeing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lincon Bordignon Somensi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Camile Cecconi Cechinel-Zanchett
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jairo Kenupp Bastos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcel Petreanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rivaldo Niero
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Valdir Cechinel-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Luisa Mota da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sérgio Faloni de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Priscila de Souza.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

.

ESM 1

(PDF 285 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Souza, P., Boeing, T., Somensi, L.B. et al. Diuretic effect of extracts, fractions and two compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid and 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone from Rubus rosaefolius Sm. (Rosaceae) leaves in rats. Naunyn-Schmiedeberg's Arch Pharmacol 390, 351–360 (2017). https://doi.org/10.1007/s00210-016-1333-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-016-1333-4

Keywords

Search

Navigation