Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo

Abstract

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 μg/mL effectively relieved CCl-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl treatment. The high serum ALT and AST levels induced by CCl were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl-induced liver damage.

Chemical profiling and pharmaco‐toxicological activity ofOriganum sipyleumextracts: Exploring for novel sources for potential therapeutic agents

“…Nonetheless, ethyl acetate extract revealed the highest content in flavonoids, which have been demonstrated to exert protective effects via multiple mechanisms. Actually, the blunting effects induced by ethyl acetate extract on the selected pro‐inflammatory and pro‐oxidant biomarkers could be due, albeit partially, to flavonoid‐induced inhibitory effects on LDH, COX‐2, 5‐HT3 receptor, and i‐NOS, whose upregulation have been causally related to inflammatory conditions and tissue damage (Chandel, Rawal, & Kaur, ; He et al, ; Herbrechter et al, ; Mousavizadeh et al, ; Zhang et al, ). The observed downregulating effects on the tested biomarkers could be also consistent with extract content in gentisic acid, rosmarinic acid, and phloridzin (Table ).…”

“…Overall, extracts downregulated all tested biomarkers of oxidative stress and inflammation, thus supporting a protective role in the colon. (Chandel, Rawal, & Kaur, 2018;He et al, 2018;Herbrechter et al, 2015;Mousavizadeh et al, 2009;Zhang et al, 2018). The ob-…”

Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress

“…However, some studies found that CCl 4 inhibits the expression of CYP2E1 due to the labilization and inactivation caused by ongoing oxidative and apoptosis [33][34][35]. Previous studies stated that CCl 4 dramatically increased the serum ALT and AST levels and led to changes in the membrane integrity of hepatocytes in mice [36,37]. In the current study, pretreatment of DIM significantly lowered the levels of liver enzymes (parameters of liver injury) and potentially stabilized the hepatic histological changes by decreasing hepatic damage in dose and time-dependent manner, suggesting that DIM may serve as a novel approach for the treatment of CCl 4 -induced liver injury in mice.…”

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

“…A trichloromethyl substitute free radical is formed by a free radical reacting rapidly with oxygen, which in turn increases with hepatotoxicity and the subsequent production of liver enzymes, leading to severe liver damage [ 30 ]. Additionally, previous studies have demonstrated that serum ALT and AST activities were increased because of CCl 4 and the membrane integrity of hepatocytes was changed in mice [ 31 , 32 ]. In the present study, maltol significantly inhibited apoptosis and the increase of liver damage indicators, and subsequently alleviated hepatic histological changes in CCl 4 -induced acute hepatic damage in mice.…”