Acute and repeated dose 28-day oral toxicity of Ruta angustifolia Pers. leaves ethanolic extract in Wistar rats

Tutik Sri Wahyuni, Hilkatul Ilmi, Ade Syamsi Kristiaji, Martiana Candra Dewi, Hanifah Khairun Nisa, Achmad Fuad Hafid, Aty Widyawaruyanti

Research output: Contribution to journalArticlepeer-review


Context: Ruta angustifolia Pers. has been used as a traditional herb among counties. The ethanol extract of R. angustifolia has proven active as an anti-hepatitis C virus in vitro. Due to the potency of this plant, a safety evaluation is necessary. Aims: To examine the acute and sub-chronic toxicity of ethanol extract of R. angustifolia leaves in rats. Methods: An acute toxicity study was done by treating 70% ethanol extract of R. angustifolia (doses of 5, 50, 300, and 2000 mg/kg of BW), while the control group received 1% Tween-80. Toxicity signs and mortality of rats for 14 days were observed. While sub-chronic (28-days repeated dose) toxicity was evaluated with 4 groups, both males and females. The three groups were treated with 70% ethanol extract of R. angustifolia at doses of 50, 500, and 1000 mg/kg BW daily for 28 days, and one group served as a control group. Biochemical, hematological, and histopathological parameters were measured after the period of treatment. Results: The acute toxicity was no demonstrated toxicity signs or mortality effects up to 14 days of the experiment. Therefore, the LD50 value of the extract was estimated to be higher than 2000 mg/kg BW. The sub-chronic assay revealed no mortality and toxicity effects, including behavior parameters, relative body weight, hematology, and biochemical at 50 and 500 mg/kg BW doses. However, a significant change was seen in the testis of all doses and the liver of the male rats treated at 1000 mg/kg BW. Histopathology assay observed the presence of activated Kupffer cells, sinusoidal dilatation, and infiltration of lymphocytes at the portal vein in the liver with 1000 mg/kg BW. Those may indicate possible toxicity in the liver at the dose of 1000 mg/kg BW. However, no toxic effect at the lower doses tested. Conclusions: These results suggest that the use of Ruta angustifolia leaves ethanolic extract is relatively safe. The application of high doses needs to be evaluated.

Original languageEnglish
Pages (from-to)437-447
Number of pages11
JournalJournal of Pharmacy and Pharmacognosy Research
Issue number3
Publication statusPublished - 2023


  • Ruta angustifolia
  • health
  • medicinal plants
  • medicine
  • toxicity assay


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