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

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.

Standardized Supercritical Co2 Extract of Acanthus Ilicifolius (Linn.) Leaves Inhibits the Pro-Inflammatory Cytokine Tumor Necrosis Factor-Α in Lipopolysaccharide-Activated Murine Raw 264.7 Macrophage Cells

“…exhibited significant anti-inflammatory activity against carrageenan-induced edema in rats [3]. 4-hydroxy-2 (3H) -benzoxazolone is a naturally occurring alkaloid of A. ilicifolius have shown to attenuate the increased TNF-α levels in an acute liver injured mice [8]. A similar effect was observed with indomethacin (1840 pg/ml) and BOA treatment on the TNF-α level.…”

“…In recent years, plant extracts obtained using supercritical CO 2 extraction technique has been widely accepted since it employs extraction of bioactive molecules at low temperature, allowing the thermolabile substance to be extracted without destruction, and results in the production of high-quality extracts that are free toxic chemical solvents. Earlier reports indicated that BOA and its structurally related analogs [7][8][9] were present in this species and the synthetic derivatives of BOA were claimed for their anti-inflammatory and antinociceptive effects [10][11][12]. BOA is also toxic allelochemical produced in plants to protect them against herbivores [13].…”

The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro‐ and anti‐inflammatory cytokines in rats with hepatic fibrosis

“…The pharmacological activity and chemical synthesis of active ingredients of HBOA have recently been reported in the literatures concerning about its anti‐inflammatory, analgesic, and antioxidant actions . The protective effect of HBOA against acute liver fibrosis in mice was also evaluated by our study group .…”

“…The whole‐plant extract has been reported to possess analgesic and anti‐inflammatory activities . In the prior study, an attempt was made to evaluate the synthesis and hepatoprotective properties of A. ilicifolius alkaloid A and its derivatives . Methanolic extract of the leaves has been reported to exhibit antioxidant, antimicrobial, hepatoprotective, and tumor inhibition activities .…”

Preventive activity of banana peel polyphenols on CCl4-induced experimental hepatic injury in Kunming mice

“…MDA is a key index of lipid peroxidation. By detecting the activity of MDA, lipid peroxidation of liver tissues may be detected, indicating the influence of CCl 4 on liver health (21). GSH is a crucial antioxidant and free radical scavenger, which is able to combine with free radicals and heavy metals to transform harmful toxins into harmless substances for excretion (22).…”