Hepatoprotective activity of Alstonia boonei (De Wild) stem bark in isoniazid-induced Wistar rats: Antioxidant, anti-inflammatory and in silico evaluations
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Date
2025
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Elsevier
Abstract
Introduction: Liver damage is mainly caused by exposure to toxic chemicals and is a global health challenge. A
variety of Alstonia species including Alstonia boonei has been used in Traditional Chinese Medicines (TCM) for the
treatment of fever, asthma and as analgesics. In this research, the potential of A. boonei stem bark ethanol extract
and ethyl acetate fraction in restoring isoniazid-induced hepatic damage in rats was studied using antioxidative
and anti-inflammatory mechanisms.
Methods: A. boonei stem bark was extracted with ethanol and fractionated with n-hexane, ethyl acetate, and
butanol. In vitro phytochemical screening and quantification, DPPH, ferrous ion chelating and ferric reducing
antioxidant activity of the extracts were carried out. Determination of erythrocyte membrane stabilizing and
inhibition of protein denaturation activity of the extracts and fractions were used to evaluate anti-inflammatory
activity. Gas chromatography- mass spectrometry (GCMS) of the most active fraction was analyzed. A total of 18
and 35 (7 groups of 5) rats were used for both acute and sub-chronic toxicity studies respectively for a period of
60 days. The control group received normal saline, while 15 mg/kg isoniazid (INH) was used to induce liver
toxicity. 25, 50 and 100 mg/kg ethyl acetate fractions (EAF), 50 mg/kg of ethanolic extract and 50 mg/kg
vitamin C were used as treatment against INH-induced toxicity. The rats were sacrificed and plasma and liver
tissues were obtained for biochemical and histological analyses. Plasma markers of hepatic function including
alanine aminotransferase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), gamma-
glutamyl transferase (GGT), albumin and bilirubin levels were determined. Activity of Liver enzyme antioxi
dants including superoxide dismutase (SOD) and catalase were also analyzed. Liver tissues were further subjected
to histological analyses. In silico molecular docking and ADMET studies were used to analyze the binding in
teractions with arginase 1 and thioredoxin reductase and physicochemical properties of the GC–MS identified
compounds.
Results: Phytochemicals including alkaloids, flavonoids and phenols were present in the plant’s extract and
fractions, while they also demonstrated antioxidant activity against DPPH radicals, and ferrous ion, with the
ethyl acetate fraction possessing the highest antioxidant and anti-inflammatory activity. The ethanolic extract
and ethyl acetate fraction of A. boonei stem bark demonstrated significant reductions in the elevated levels of
plasma liver function enzymes and were also able to significantly restore the activities of enzyme antioxidants
(SOD and catalase). Furthermore, restorations in liver histoarchitecture were observed in groups treated with the
extract and fractions. In silico analysis revealed high negative binding interactions between compounds identified
in the extract and arginase 1and thioredoxin reductase. While ADMET analysis shows good pharmacodynamic
and physicochemical properties of the identified compounds
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Adesina, A. F., Apata, J. T., Babalola, O. O., Otuechere, C. A., Adekola, M. B., Ogunleye, G. S., & Asaolu, F. (2025). Hepatoprotective activity of Alstonia boonei (De Wild) stem bark in isoniazid-induced Wistar rats: Antioxidant, anti-inflammatory and in silico evaluations. Pharmacological Research-Modern Chinese Medicine, 14, 100558.