Acute and developmental toxicity of embelin isolated from Embelia schimperi Vatke fruit: In vivo and in silico studies.

ABSTRACT

Background: Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the in silico, acute, and developmental toxicity profiles, has yet to be thoroughly investigated. Hence, this study aims to assess these toxicity profiles. Materials and Methods: In silico and in vivo experimental studies were conducted on embelin isolated from the fruits of Embelia schimperi Vatke. In silico toxicity predictions were computed using the ProTox model. The in vivo experiment was done by administering 5000 mg/kg of embelin to a single female albino Wistar rat, followed by three female rats in the absence of death, to determine the mean lethal dose (LD50). Afterwards, three groups of pregnant rats were treated with embelin at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg for the developmental toxicity test. Vehicle and ad libitum control groups were used to compare the acute and developmental toxicity variables. Results: In silico toxicity predicted that embelin is free from hepatotoxic, carcinogenic, mutagenic, and cytotoxic effects. No inhibitory effect on hERG channels was observed. It has an immunotoxic property and an inhibitory effect on the CYP2D6 enzyme. Since mortality and signs of toxicities were not observed after treatment with 5000 mg/kg, the mean lethal dose (LD50) is determined to be > 5000 mg/kg. There was no significant difference in the morphological scores or number of somites among experimental animals. None of the embryonic systems possessed developmental delays. Nevertheless, the crown-rump length of the high-dose group became significantly shorter. Maternal food intake and weight gain exhibited significant dose-dependent differences between embelin-treated animals and controls. The number of implantations was significantly low in the treatment group, accompanied by a higher frequency of prior resorption. Conclusion: Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further in vitro and in vivo studies need to be conducted to understand the mechanism behind the toxicity of embelin.