Sub-chronic toxicity of the aqueous leaf extract of Ocimum lamiifolium Hochst. ex Benth on biochemical parameters and histopathology of liver and kidney in rats: in vivo and in- silico toxicity studies

The aerial part of Ocimum lamiifolium is commonly used in Ethiopian traditional medicine. Although this plant is mostly used in traditional medicine, its safety profile has not been documented yet. The aim of this study was to assess the sub-chronic toxicity of O. lamiifolium aqueous extract in rats and to determine the toxicity profile of GC–MS identified bioactive compounds obtained from essential oil of O. lamiifolium using in silico toxicity methods.

Eighty rats (40 male and 40 female) were randomly assigned to four groups of ten rats per sex/group. For 90 days, Groups I-III received 200, 400, and 600 mg/kg bw of aqueous extract of O. lamiifolium, respectively. Distilled water was given to Group IV (control). Clinical observations, food intake, and rat weight were all recorded during the experiment. In addition, several biochemical parameters, organ weight, and histology of the liver and kidney were all evaluated. For the in-silico toxicity study, GC–MS identified bioactive compounds in O. lamiifolium essential oil were obtained from published articles. The compounds two-dimensional structures were constructed using Chemdraw. The two-dimensional structures were converted into a simplified molecular input line entry system (SMILES) using the Swiss ADMET web tool. Furthermore, the toxicity parameters were predicted using the ProTox II server.

The administration of an aqueous extract of O. lamiifolium leaves significantly (p < 0.05) reduced the test animals' food intake and body weight gain. In the high dose (600 mg/kg bw) treated group, the serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly increased (p < 0.05). In female rats given 600 mg/kg bw of O. lamiifolium, the levels of serum urea were also increased. In addition, rats given 600 mg/kg bw had significantly lower blood glucose levels than the control group (p < 0.05). Doses up to 400 mg/kg bw didn’t bring a significant change to the histology of the liver. However, in the high dose (600 mg/kg bw) treated group, some female rats' livers showed mild sinusoidal and central vein dilatation, as well as parenchymal necrosis. our findings showed that all compounds derived from the essential oil of O. lamiifolium showed no mutagenicity or cytotoxicity. However, 30% of the compounds tested were hepatotoxic, 20% carcinogenic, and 20% immunotoxin.

Our findings showed that oral administration of O. lamiifoliums aqueous extract up to a dose of 400 mg/kg bw is not toxic. However, high-dose (600 mg/kg bw) significantly affected the food consumption and weight gain of the experimental rats and the serum concentration of some liver and kidney enzymes were also significantly increased. Additionally, a considerable proportion of the tested compounds were predicted to be hepatotoxic, carcinogenic and immunotoxin. Furthermore, before employing O. lamiifolium preparations as drugs, a chronic toxicity research on the essential oil as well as its components that exhibited toxicity in the in-silico toxicity study is needed. Finally, use high doses of O. lamiifolium leaves with caution.