TY - JOUR
T1 - Acute and repeated dose 28-day oral toxicity of Ruta angustifolia Pers. leaves ethanolic extract in Wistar rats
AU - Wahyuni, Tutik Sri
AU - Ilmi, Hilkatul
AU - Kristiaji, Ade Syamsi
AU - Dewi, Martiana Candra
AU - Nisa, Hanifah Khairun
AU - Hafid, Achmad Fuad
AU - Widyawaruyanti, Aty
N1 - Publisher Copyright:
© 2023 Journal of Pharmacy & Pharmacognosy Research.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Ruta angustifolia
KW - health
KW - medicinal plants
KW - medicine
KW - toxicity assay
UR - http://www.scopus.com/inward/record.url?scp=85164528606&partnerID=8YFLogxK
U2 - 10.56499/jppres23.1609_11.3.437
DO - 10.56499/jppres23.1609_11.3.437
M3 - Article
AN - SCOPUS:85164528606
SN - 0719-4250
VL - 11
SP - 437
EP - 447
JO - Journal of Pharmacy and Pharmacognosy Research
JF - Journal of Pharmacy and Pharmacognosy Research
IS - 3
ER -