Safety Evaluation of the Aqueous Extract of the Mixture of <i>Persea americana</i> (Lauraceae), <i>Cymbopogon citratus</i> (Poaceae), Fruits of <i>Citrus medica</i> (Rutaceae), and Honey in Wistar Rat

As part of the valorization of traditional medicine drugs, toxicological studies were carried out on the mixture of the aqueous extract of <i>Persea americana, Cymbopogon citratus, Citrus medica</i>, and honey, a traditional mixture recognized for its antihypertensive activities. The experiments were conducted following modified OECD protocols 425 and 407 for acute and subchronic toxicity tests, respectively. For the acute toxicity, rats were divided into 3 groups of 6 rats (3 females and 3 males). They were given 2 single different doses of aqueous extract of the mixture and distilled water (2000 and 5000 mg/kg, 10 mL/kg). They were observed for the first 24 h and during 14 days. Clinical signs and nature of feces were evaluated. Concerning the subchronic toxicity, six groups of 10 animals each (5 males and 5 females) were used for each dose. The animals of group 1 received distilled water (10 mL/kg), and the animals of groups 2, 3, and 4 received the aqueous extract of the mixture (150, 300, and 600 mg/kg). The animals of groups 5 and 6 were normal satellite control and satellite extract 600 mg/kg. They received, respectively, distilled water (10 mL/kg) and the aqueous extract of the mixture (600 mg/kg). These last two groups were observed 14 days more than the other groups after complete cessation of all treatments. Clinical signs were evaluated and marked by normal fecal matter throughout the experimental period, with a nonsignificant weight variation. After the experiment, rats were sacrificed. For the subchronic toxicity evaluation, blood samples and some organs were taken. Relative organ was calculated, and hematological and biochemical parameters were also evaluated as well as histological sections of organs (pancreas, lungs, liver, kidneys, and spleen). Concerning the acute toxicity, some organs such as the pancreas, lungs, liver, kidneys, and brain were taken and weighed and relative weights were calculated. Administration of the aqueous extract of the mixture daily and for 28 days at the highest dose (600 mg/kg) led to significant increases in the weight of the kidneys (16.25%; <i>p</i> < 0.05) and lungs (58.72%; <i>p</i> < 0.001), and on the other hand, a significant drop in the relative weight of the spleen was observed (49.87%; <i>p</i> < 0.01). A significant increase in the level of leukocytes (<i>p</i> < 0.001) in animals of both sexes treated with the aqueous extract of the mixture at the highest dose was recorded. Treatment of animals with the extract at the highest dose resulted in a significant decrease in triglycerides (<i>p</i> < 0.05) in males. The microarchitecture of histological sections of the organs did not present any notable abnormality apart from a leukocyte shift at 600 mg/kg. The aqueous extract of this mixture is not toxic at the doses used traditionally (50, 100, and 150 mg/kg).