CCl₄-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Abstract

Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl4. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl4-treated rats. Compared to rats treated with CCl4 alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.

Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

“…Because genetic ablation of Nrf2 potentiates the severity of liver injury in experimental animals [38][39][40], Nrf2 is regarded as a key transcription factor coping with oxidative stress and inflammation in the liver. Consistent with previous reports [41,42], the results presented here showed that CCl 4 downregulated hepatic mRNA levels of Nrf2, resulting in the depletion of hepatic glutathione, and reduced SOD and catalase activities, which may facilitate liver injury via the disruption of the antioxidant response. Moreover, our preliminary results using HepG2 cells (hepatocyte-surrogate cells) indicate that MLD significantly transactivated antioxidant response element-harboring reporter genes and induced the mRNA level of NAD(P)H: quinone oxidoreductase 1 in a concentration-dependent manner [23].…”

Suaeda vermiculata Aqueous-Ethanolic Extract-Based Mitigation of CCl4-Induced Hepatotoxicity in Rats, and HepG-2 and HepG-2/ADR Cell-Lines-Based Cytotoxicity Evaluations

“…The oral supplementation of antioxidants for liver disorders has been studied, and several non-enzymatic antioxidants, (e.g., ascorbic acid, α-tocopherol, silibinin, naringenin, quercetin, curcumin, resveratrol, products of phenolic, flavonoid, tannin, and carotenoid types) have been exploited [ 21 , 22 , 23 ], and the plant-origin secondary metabolite-based antioxidants have revealed promising in vivo therapeutic effects on liver disorders in studied animal models [ 24 ], though clinical studies were deemed inconclusive [ 23 ]. However, the protective roles of these antioxidants on the liver, in experimentally induced-liver injury and toxication, have been investigated for various pure, single component natural products, and on the naturally-sourced plants’ extracts, as well as mixtures of synergistic natural products containing antioxidants of a structurally-varied chemical nature, and were found to be effective [ 9 , 25 , 26 , 27 , 28 ].…”

Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats

“…CYP2E1 metabolizes CCl 4 to free radicals such as trichloromethyl and carbene. These free radicals degenerate the hepatocytes by binding to the nucleic acids and cell membrane as well as elevate the serum levels of aminotransferases via inducing oxidative stress and mitochondrial damage [20]. In this research, in the CCl 4 group the serum levels of aminotransferases were considerably greater than the control group which pointed to the liver injury.…”