Study On The Detoxification And Mechanism Of Licorice

Chinese medicine Radix Glycyrrhiza derives from the root and rhizome of Glycyrrhiza glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata, which are the perennial leguminous grass. Its property is sweet and mild-natured, and it has many functions, such as tonifying spleen, heat-clearing and detoxifying, relieving cough, relieving spasm and pain, moderating the property of herbs, etc. As a traditional Chinese medicine, glycyrrhiza was frequently used in Chinese medicine prescriptions, thus it was lauded as "ten prescriptions nine grass". Detoxification is one of the most important function of glycyrrhiza, and was recorded in many classics of traditional Chinese medicine. The modern studies on the detoxification mechanism are mainly as following:1. Glycyrrhiza can combined with poisons to reduce the dissolution of poisons; 2. Certain ingredients of glycyrrhiza can react with poisons to attenuate and detoxicate the poisonousness; 3. Use its pharmacological action against or alleviate the physiological effects, to achieve its apparent effects on detoxification. The deficiency of the above research is limited to the specific toxins, and cannot explain the nonspecific and broad-spectrum effects, besides, they may be the indirect detoxification ways. We need to research the important clear way of poisons, namely the metabolism way. This study are focused on the detoxification mechanism of glycyrrhiza from the metabolism and clear way, which can provide the modern science explanation.In this research, we chose glycyrrhiza extract (GE), glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) as the experimental drugs, explored the antidotal effect though the cell and animal levels, and further clarified the antidotal mechanism, which may deepened the understanding of glycyrrhiza traditional applications. The main results were as follows:(1) MTT colorimetric method was used in the cell toxicity test, and the concentration below IC20 were adopted for the subsequent experiments. The results showed that, the IC20 values of GE, GL and GA were 52.33?g/mL,24.95?M and 18.23?M respectively. So we took 1.6?g/mL,8?g/mL,40p,g/mL of GE,0.8?M,4?M, 20?Mof GL,0.4?M,2?M, 10?M of GA for the subsequent experiments.(2) The detoxification effects of GE, GL and GA to Adriamycin, Realgar and 3, 4-Dichloronitrobenzene on HepG2 cells were detected by MTT method, and IC50 was chosen as the detection index. The results showed that, GE (8?g/mL), GL (4?M), GA (2?M) could increase the IC50 of Adriamycin (ADR) from 4.51?g/mL to 6.47?g/mL 5.11?g/mL and 5.29?g/mL respectively; enhance the IC50 of Realgar from 6.09×103?M to 7.68×103?M,9.88×103?M and 6.13×103?M; and improve the IC50 of 3, 4-Dichloronitrobenzene (DCNB) from 58.36?M to 63.36?M,81.21?M and 72.62?M. The results indicated that GE, GL and GA can improve the IC50 value of poisons, decrease the cell toxicity.(3) Establishing the poisoning mice model, fed the mice with GE, then detect the detoxification effect in mice. The results showed that, compared with the model group, GE could decrease the content of poison in mice plasma; decrease the content of the liver biochemical indexes ALT and the kidney biochemical indexes BUN; in addition, it also significantly decrease the rate of weight, the index of liver and kidney; the observation of liver tissue pathological slices found that GE can protect the liver cells in certain extent.(4) Using the Elisa kits to detect the influence of GE, GL and GA to the content of CYP3A4, GST in HepG2 cells and mice. The results showed that all doses of GE, GL and GA could enhance the content of CYP3A4 in HepG2 cells (P<0.05 or P<0.01), and all doses of GL and GA could enhance the content of GST, but the low dose of GE could decrease the content of GST (P<0.05); the study on the detoxification enzymes in mice liver showed that GE could improve the contents of CYP3A4 and GST effectively, and showed a dose-independence manner.Conclusion:GE, GL and GA could decrease the toxicity of poisons on HepG2 cells, improve the biochemical indexes of liver and kidney, improve the state of liver pathology, and protect the liver from the poison damage. In addition, glycyrrhiza can increase the contents of CYP3A4 and GST in HepG2 cells and mice liver, improve the biological conversion rate, reduce the toxin concentration, so as to achieve detoxification efficacy. This experiment research results may provide certain scientific theoretical basis and explanation for the traditional detoxification application of glycyrrhiza.