Synthesis and hepatoprotective properties of Acanthus ilicifolius alkaloid A and its derivatives

Liu,Lin; Fan,Hui; Qi,Ping; Mei,Yan; Zhou,Lijuan; Cai,Liping; Lin,Xing; Lin,Jun

doi:10.3892/etm.2013.1189

Synthesis and hepatoprotective properties of Acanthus ilicifolius alkaloid A and its derivatives

Authors:
- Lin Liu
- Hui Fan
- Ping Qi
- Yan Mei
- Lijuan Zhou
- Liping Cai
- Xing Lin
- Jun Lin
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Affiliations: Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Shanghai Jiaotong University, Shanghai 200240, P.R. China, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: June 28, 2013 https://doi.org/10.3892/etm.2013.1189
Pages: 796-802

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Abstract

Acanthus ilicifolius alkaloid A (4-hydroxy-2(3H)benzoxazolone, HBOA) is a naturally occurring compound that has been separated from Acanthus ilicifolius. Previous studies have reported the beneficial effects of HBOA on HSC-T6 cells. This study was undertaken in order to synthesize HBOA and two of its derivatives, specifically, 4-acetoxy-2(3H)-benzoxazolone (AcO-BOA) and 3-acetyl-4-acetoxy‑2-benzoxazolone (TC-3), and to investigate the hepatoprotective potentials of these three compounds on CCl4-induced liver injury in mice. HBOA was prepared from 2-nitroresorcinol by a 'one pot' reduction and subsequent cyclization with urea. The acyl derivatives, AcO‑BOA and TC-3, were prepared from HBOA using a substitution reaction. The compounds were synthesized with good yields (63.08-68.22%). An acute liver injury model was established by administering CCl4 intraperitoneally to Kunming mice. The mice were then intragastrically administered bifendate (150 mg/kg) or the synthesized compounds at three different doses (200, 100 and 50 mg/kg). The treatment with CCl4 was observed to increase the levels of aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH) and malondialdehyde (MDA) and decrease the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (Gpx) in the liver tissues of the mice. Furthermore, treatment with CCl4 elevated the expression level of the proinflammatory mediator TNF-α. However, HBOA and its derivatives attenuated the changes induced by CCl4. Furthermore, CCl4‑induced histopathological changes were reduced by treatment with these compounds. These results suggest that HBOA and its acyl derivatives are able to significantly alleviate the hepatotoxicity induced by CCl4 in mice.

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