The Hepatoprotective Effect Of Radix Puerariae And Puerariae Flos Against The Alcoholic Liver Injury In Mice And Its Mechanisms

The main objectives of this subject is to discuss the effect of Radix Puerariae andPuerariae Flos on the acute and chronic alcoholic liver injury in mice, and draw a comparisonabout the sober-up and hepatoprotective effect between Radix Puerariae and Pueraria Flos.To compare the sober-up effect of Radix Puerariae with Puerariae Flos, the sober timeand ethanol concentration were determined. Firstly, Radix Puerariae and Puerariae Flos wereextracted respectively by water and ethanol, and freeze-dried to be four kinds of crudeextracts of Radix Puerariae and Puerariae Flos (PRW/PRE/PFW/PFE). The model group wasadministered intragastrically saline10mL/kg.bw, while the the low, medium and high dosegroups were respectively given2.5,7.5and10g/kg bw of Radix Puerariae or Puerariae Floscrude extracts;30mins later, each group was afforded ethanol5.75g/kg.bw. The results showthat Radix Puerariae and Puerariae Flos have a certain sober effect on the drunken mice. Thesober-up effect of Radix Puerariae is better than that of Puerariae Flos, and the PRE is betterthan PRW as well as the effect of higher dose is better than that of lower dose.In the chronic alcoholic liver injury experiment, the hepatoprotective effect of RadixPuerariae extract(PR) and Puerariae Flos extract(PF) on liver are firstly evaluated by thephysiological and pathological indicators. On the results of previous indicators, themechanisms of PR and PF on alcoholic liver were discussed from the following three aspects:oxidative stress, lipid metabolism and the inflammatory signal transduction. Mice weredivided into seven groups: blank group, model group, PRL and PRH groups (100and300mg/kg.bw total flavones of PR respectively), PFL and PFH groups (100and300mg/kg.bwtotal flavone of PF respectively), and the positive group(FB,500mg/kg.bw). The blank groupwas intragastricly administered distilled water while the other groups were given50%ethanol. A hour later, the blank group and model group were still given distilled water, and therest groups were given corresponding dose of PR or PF solution in6mL/kg.bw. And the micewere killed after11weeks. The chronic experimental results suggest that PR and PF caninhibit the increasing activity of alanine aminotransferase and aspartate aminotransferasecaused by ethanol, exhibiting a hepatoprotective effect on the mice. In the aspect of oxidativestress, PR and PF can not only elevate glutathione level, increasing the antioxidant capacity ofliver, but also reduce the endotoxin (LPS) concentration in blood and inhibit mRNAexpression of CYP2E1gene, thus reduce free radicals from macrophage and CYP2E1toimprove the damage of oxidative stress. Furthermore, the antioxidant capacity and theinhibition of CYP2E1expression of PF is stronger than PR. In the aspect of lipid metabolism,PR and PF can raise the mRNA expression level of AMP-activated protein kinase alpha2(AMPKα2), but there are some differences in the regulation of lipid metabolism between PRand PF: The PR can significantly inhibit the transcriptional activity of sterol regulatoryelement binding protein1c (SREBP-1c) under the the activated AMPKα2, reducing thesynthesis of triglycerides (TG). However, PF may be as a ligand which can activate theperoxisome proliferator-activated receptor alpha (PPARα) to increase the PPARα mRNAexpression, which can also indirectly be regulated by the activated AMPKα2,so that it can reduce the lipid level. And PR has a better lipid lowering effect than PF. In the aspect ofInflammatory signal transduction, PR and PF can not only reduce the LPS recognitionreceptors Toll-like receptor4(TLR4) and its downstream adapter protein molecule myeloiddifferentiation protein88(MyD88) mRNA expression, but also improve the nuclear factorkappaB inhibitor α (IκBα) level, inhibiting the inflammatory signal transduction. And PF hasa stronger anti-inflammation effect than that of PR.All the results suggest that Radix Puerariae and Puerariae Flos have a goodhepatoprotective effect on the alcoholic liver. PR may inhibit the transcriptional activity ofSREBP-1c and reduce the triglyceride synthesis through the activated AMPKα2. While PF canboth increase the antioxidant capacity of liver and inhibit the CYP2E1mRNA expression toreduce the oxidative damage; Furthermore, PF may be as the ligand of PPARα to raise themRNA expression of PPARα, which can also indirectly be regulated by the activatedAMPKα2, to promote fatty acid oxidation and reduce the triglyceride level.