Abstract
The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human.
Highlights
The liver plays an essential role in some of the vital body functions including protein synthesis, detoxification, and the metabolism of various consumed or absorbed substances [1,2,3]
The liver tissues of mice treated with CCl4 showed multiple histopathological changes manifested by the infiltration of mononuclear inflammatory cells mainly macrophage and lymphocytes mixed with multiple neoplastic cells and seen as multifocal granuloma like lesions within the whole hepatic parenchyma similar to ehrlich ascites carcinoma cells (EACs)
We found that administration of CCl4 to mice decreased the antioxidant capacity of mouse liver as evidenced by the declined levels of superoxide dismutase (SOD), CAT and Glutathione peroxidase (GPx), which were in agreement with the earlier results [50,51,52]
Summary
The liver plays an essential role in some of the vital body functions including protein synthesis, detoxification, and the metabolism of various consumed or absorbed substances [1,2,3]. Flavonoids are secondary plant metabolites responsible for colour and aroma of flowers They interfere with multiple signal transduction pathways involved in liver diseases leading to inhibition of oxidative stress, apoptosis, and angiogenesis [17]. As part of our ongoing research to identify a new effective and functional natural component [33,34,35,36] with high availability and low cost, the present study aims to investigate the anti-oxidant, anti-apoptotic, and anti-proliferative activities of 3,5-dihydroxy-4 ,7-dimethoxyflavone (Figure 1) isolated from T. aphylla. The long-term goal is to develop a potent pharmaceutical agent that inhibits the production and activation of free radicals and acts against CCl4-induced liver injury in mice. The long-term goal is to develop a potent pharmaceutical agent that inhib3itosf 16 the production and activation of free radicals and acts against CCl4-induced liver injury in mice
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