1Faculty of Medicine, AIMST University, Bedong-Kedah, MALAYSIA.
2Department of Biochemistry, School of Medicine, College of Medicine and Health Science, Jigjiga University, Jigjiga, ETHIOPIA.
3Department of Botany, Yadava College, Madurai, Tamil Nadu, INDIA.
4Department of Plant Biology and Plant Biotechnology, Presidency College (Autonomous), Chennai, Tamil Nadu, INDIA.
5Department of Zoology, College of Science, King Saud University, PO Box-2455, Riyadh, SAUDI ARABIA.
6Department of Botany and Microbiology, College of Science, King Saud University, PO Box-2455, Riyadh, SAUDI ARABIA.
7Departments of Pathology and Cell Biology, University of South Florida College of Medicine, Tampa, FL 33612, USA.
8Department of Chemistry and Biosciences, Srinivasa Ramanujan Centre, SASTRA (Deemed University), Kumbakonam, Tamil Nadu, INDIA.
# Equally contributed first authors.
Corresponding author.
Equally contributed first authors.
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ABSTRACT
Introduction
Ziziphushamur Engl. (Vernacular name: Xamurgob) is a thorny shrub native to Ethiopia, Kenya and Somalia. The plant is extensively used in the traditional system of the Somali region in the treatment of jaundice and mental illness. Lack of prior experimental studies and wide usage in traditional medicine demands the toxicological evaluation of Ziziphus hamur Engl. The aim of this study was to evaluate the safety of Ziziphus hamur root bark by sub-acute toxicity study in male albino wistar rats. Investigation of cytokine levels were done to check for cytokine modulatory role of Ziziphus hamur, thereby providing insights on the toxicity profile and for the therapeutic property of Ziziphus hamur.
Materials and Methods
The aqueous extract of Z. hamur root bark was used for this study. The sub-acute toxicity study was carried out as per OECD guidelines. 24 albino Wistar rats (only males) were grouped and subjected to sub-acute toxicity study with orally administered extract doses of 100, 200 and 400 mg/kg body weight for 28 days. The biochemical parameters for hepatic and renal injury and hematological parameters were assessed. The evaluation of cytokines IL-6, TNF-α, INF-γ, IL-2 and IL-10 were done by ELISA to document the toxic responses in vivo. The histological studies of the liver and renal tissues were performed to check tissue damage caused.
Results
We noticed no mortality, no behavioural changes and physical changes in sub-acute toxicity experimental rats proving the preliminary evidence about the safety of the Z. hamur root bark extract. No noticable changes in water and food intake among the experimental rats proved the non-toxic nature of Z. hamur root bark extract. Body weight gain in the test group and control group of experimental rats were similar without significant difference. The biochemical analysis for liver toxicity, renal toxicity and lipid profile parameters also proved the evidence for non-toxic nature and healthier effect of Z. hamur by significant decrease in marker enzyme activities, TGL, LDL, VLDL and significantly higher level of HDL. The hematological parameters assessment showed significant beneficial effects in the treatment of the extract at the dose of 400 mg/kg body weight. The levels of IL-6 (7.68% decrease), TNF-α (7.58% decrease), IL-2 (3.46% increase) and IFN-γ (7.79% decrease) were altered without statistical significance and IL-10 was significantly increased (50.32%; p <0.001) compared to the control suggesting that Ziziphus hamur is non-toxic and safe for the use of various pathological treatments.
Conclusion
Results of this study concluded that Z. hamur has no toxicity, revealed by biochemical, haematological and histopathological parameters, up to a dose of 400 mg/kg body weight in experimental animals. Changes in the cytokine levels in sub-acute toxicity studies supported the cytokine modulatory effect of Ziziphus hamur that could benefit towards its therapeutic potential.