Acute and subchronic toxicological profile of Ziziphus jujuba Mill. bark methanolic extract toward Swiss albino rats

Abstract

Ziziphus jujuba is a medicinal botanical with various pharmacological properties against cardiovascular diseases, respiratory system diseases, gastrointestinal problems, dysentery, and diarrhea. Despite its exhaustive use for medicinal aims, no study has yet been directed to evaluate this plant's potentially toxic profile. The present work focused on the acute and subchronic toxicity of Z. jujuba bark extract.

The acute oral toxicity was performed using the OECD guideline 425; Z. jujuba bark extract was administered to female rats at a single dose of 5000 mg kg^-1 body weight. The subchronic acute oral toxicity was carried out according to OECD guidelines 407; Z. jujuba bark extract was administered to male and female rats at doses of 250, 500, and 1000 mg kg^-1 bw; after 28 days of Z. jujuba bark extract daily administration, the animals were sacrificed. Hematological parameters, serum and urinary biochemical parameters, and histological sections of the liver and kidneys were assessed.

Administration of the single-oral dose of Z. jujuba bark methanolic extract did not cause any death in rats, and the LD₅₀ was found to be greater than 5000 mg kg^-1 bw. The repeated administration of Z. jujuba bark methanolic extract at 250, 500, and 1000 mg kg^-1 bw did not induce any significant perturbation of the white blood cells, lymphocytes, red blood cells, hemoglobin, hematocrit, and platelets in rats as compared to the controls. For the lipid parameters, namely triglycerides and cholesterol, no significant difference was recorded between the profiles of the treated and untreated groups of animals. Likewise, we registered non-significant changes in renal parameters such as creatinine, urea, and proteins; this was confirmed by the histological sections, which showed a normal kidney structure. Besides, we did not observe any significant modification in the values of liver parameters, ALT and AST. This finding was further confirmed by the histological examination of the liver, which revealed the organ's normal structure.

Finally, for single-oral administration, Z. jujuba bark extract is almost non-toxic. For repeated oral administration, Z. jujuba bark extract is safe at doses up to 1000 mg kg^-1 bw over a 28-day period.