Acute and repeated-doses (28 days) toxicity study of Hypericum polyanthemum Klotzsch ex Reichardt (Guttiferare) in mice

Hypericum polyanthemum, a South Brazilian species showed antidepressant-like and antinociceptive effects in rodents. Since limited information is available on the toxicity and safety profile of the Hypericum genus, we therefore investigated whether H. polyanthemum cyclo-hexane extract (POL) treatment could be associated with toxicity in preclinical setting using mice as an experimental model. These toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). Animals received POL single dose (2000 mg/kg, p.o.) or daily for 28-days (90, 450 and 900 mg/kg, p.o.). Acute toxicity study did not detect any clinical signs, changes in behavior or mortality. In repeated dose toxicity study, POL affected the body weight gain and induced biochemical, hematological and liver histological changes at 450 and 900 mg/kg. Mice treated with POL 90 mg/kg did not show any toxicity signs. In conclusion H. polyanthemum can be classified as safe (category 5) according to OECD acute toxicity parameters. However, the alterations observed after repeated treatment with high doses suggest that the liver could be the target organ on potential H. polyanthemum toxicity and point to the need of further toxicity studies.