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 Schmiedebergs Arch Pharmacol. 2017 Apr;390(4):351-360. doi: 10.1007/s00210-016-1333-4. Epub 2016 Dec 24.

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.

Keywords: Calcium; Creatinine; Flavonoids; Folk medicine; Prostaglandin; Triterpenes.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / urine
  • Diuretics / pharmacology*
  • Flavones / pharmacology*
  • Indomethacin / pharmacology
  • Male
  • Muscarinic Antagonists / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Rats, Wistar
  • Rubus*
  • Triterpenes / pharmacology*

Substances

  • 2,3,19-trihydroxy-12-oleanen-28-oic acid
  • 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone
  • Cyclooxygenase Inhibitors
  • Diuretics
  • Flavones
  • Muscarinic Antagonists
  • Plant Extracts
  • Triterpenes
  • Atropine
  • Nitric Oxide Synthase
  • Dinoprostone
  • NG-Nitroarginine Methyl Ester
  • Indomethacin