| Comprehensive learning of non-alcoholic steatohepatitis(NASH) in both modern medicine and traditional chinese medicine (TCM)is demonstrated through literature review,and animal experimental study in this paper. Efficacy and mechanism of Yinchenhao Decoction is explored in the animal experimental study.The research provided a basis to further reveal the mechanism of Yinchenhao Decoction and to explore new Cuban side to enhance by the side of the value of academic research in the field and clinical therapeutic levels.1Literature reviewThrough literature analysis in recent10years both at home and abroad, the etiology,pathogenesis,and treatment of modern medicine, also etiology and pathogenesis, syndrome differentiation, physical sciencetreatment progress of TCM have been review.2Effects of Yinchenhao Decoction on mice with NASH on MCD dietObjectiveTo investigate the efficacy of Yinchenhao Decoction(YCHD) on mice with non-alcoholic steatohepatitis (NASH) on MCD diet.MethodThe C57BL/6mice was fed with MCD diet for2weeks to make NASH mice model. After modeling, the treatment group were intervened by YCHD high, middle (conventional dosage), low dose for4weeks. Then the change of serum transaminase, serum lipid, liver lipid, Lipid peroxidation indexes and the liver pathology had been detected to observe the efficacy.Outcome(1) General condition and pathomorphology:The hepatic steatosis and inflammation,also liver index were increased, body weight was reduced in model group, but improved in the treatment group compared with model group. NAS score was reduced significantly at the same time.And there was no significant difference between the all treatment group. Liver index was reduced significantly in the high and middle dose groups of YCHD group.(2) Serum transaminase:Compared with blank control group, the serum ALT, AST in model group were obviously increased. The serum ALT decreased in YCHD middle dose group, and there was no signicficant difference in improving liver function them. The indexes had no signicf icant change in high and low dose groups of YCHD. (3) Lipid:Serum TC, TG, HDL-C was reduced, LDL-C and TG in liver was increased in the model compared with blank control group. The high and middle dose groups of YCHD could decrease serum TC, TG, LDL and liver TG significantly, the low dose of YCHD could decrease serum TC, LDL and liver TG. There was no signicficant change in serum HDL of all groups.(4) Lipid peroxidation indexes:In model group, the MDA content in liver were increased, the GSH-PX and SOD was decreased compared with the blank control group. In treatment groups, the MDA were decreased significantly. As the GSH-PX and SOD, there was no significant difference among all groups.ConclusionThe three dose of YCHD could improve the liver pathological change, decrease liver lipid and MDA level significantly. The high and middle dose was good at reducing liver index and blood lipid, which was better than the low dose at blood lipid. Only the middle dose could reduce the serum ALT. Overall, the efficacy of conventional dose was the best among them, and the high dose is better than the low.3Research of efficacy and therapeutic mechanism of YCHD to NASH for rat fed on high fat dietObjectiveTo investigate the efficacy and therapeutic mechanism on regulating insulin resistance of YCHD on rat with NASH on high fat diet.MethodsNASH model in SD rats was established by feeding high fat diet for8weeks, After modeling, the treatment and control group were intervened by YCHD high, low(conventional dose) dose and compound yiganling for4weeks, natural recovery group was restored to normal diet. Then the change of serum transaminase, serum lipid,fas ting blood glucose, fasting insulin,liver lipid, lipid peroxidation indexes,the liver pathology and expression levels of DGAT-2、PKC-ε、INS-1、TNF-α、mRNA of the liver had been detected to observe the efficacy and mechanism.Outcome(1) Pathomorphology change:After treatment, the steatosis, lobular inflammation, ballooning and total scores all decreased by the low dose of YCHD and natural recovery group s ignif icant ly. The high dose of YCHD and control group improved the lobular inflammation and ballooning. (2) Serum transaminase:The serum transaminase was increased in YCHD high dose group,and the serum AST increased in control group. The low dose of YCHD reduced the serum transaminase but there was no signicficant change.(3) Lipid:Serum TC, TG, LDL-C was reduced in the low dose of YCHD and control group, TG reduced in the high dose, TG reduced in the natural recovery group. There was no signicficant change on HDL-C in the treatment groups,while increased in the natural recovery group. ALL groups could reduced FFA contents in the liver and there was no signicficant difference between them, the low dose of YCHD could decrease DAG, TG contents in the liver, the high dose and compound yiganling decrease DAG signicficantly.(4) FBG,FINS and peripheral insulin resistance:The level of FBG and FINS in serum of all treatment groups were significantly lower than those of model group. There was no significant difference among them. ALL groups could reduce the level of HOMA-IR, but there was no significant change.(5) Lipid peroxidation indexes:The activities of serum GSH-PX and level of serum and1iver MDA were significantly improved in the low dose of YCHD, which was better than that of the high dose and compound yiganling group. GSH-PX in liver had no significant change in all treatment groups. While the natural recovery group could increase GSH-PX in liver also the other lipid peroxidation indexes. There was no significant change on SOD in all groups.(6) Hepatic insulin resistance and inflammation:The expression of PKC-5and TNF-a in liver was significantly reduced, the expression of IRS-1was increased in all treatment groups.There was no significant difference among them. Meanwhile, the low dose of YCHD could also reduce the expression of Dgat-2in liver, but the level of it had no signif icant change in high dose and yiganling group.Conclusion(1) YCHD has good efficacy on NASH rats feeding by high fat diet with pathogenesis of "two-hit" mechanism by improving the steatosis, disorders of glucose and lipid metabolisin, also peripheral insulin resistance. Enhancing antioxidant ability and clearing free radical metabolites to inhibit lipid peroxidation. YCHD conventional dose is better than high dose on rats NASH model. On enhancing the periphery antioxidant capacity and alleviating liver fat accumulation, YCHD conventional dose was better than compound yiganling piece. On enhancing liver antioxidant capacity, compound yiganling tablets was better than YCHD conventional dose.(2) There might be certain side effects due to excessive use of high dose. The compound yiganling sheet had certain side effects also, but the specific cause could not yet be conclusive. The high dose was quite to compound yiganling piece. On enhancing liver antioxidant capacity, compound yiganling tablets was better than YCHD high dose.(3) By regulating the related factors and inflammatory factors on signaling pathway of DAG-PKC ε, YCHD could improve he patic insulin resistance. This is part of the mechanism of the regulation of insulin resistance by YCHD.(4) Rat model in the case of non-pharmacological interventions, had better recovery in blood lipids, liver lipid metabolism, lipid peroxidation degree and the outer periphery of antioxidant capacity, but could not restore itself without a drug intervention in repairing liver cells, uptake and utilization of glucose, regulation of insulin secretion in short-term.4Research of interaction by disassembling YCHD to NASH for rat fed on high fat diet by orthogonal designTo observe the difference of efficacy of each herb and combinations in YCHD on NASH for the correlation between drugs and NASH, interaction between drugs.MethodMethods of orthogonal design and disassembling the prescription was taken in this study, three factors and two level are confirmed, according to orthogonal layout L8(2’), rats were divided into8groups and were intervened by corresponding herb and combination for4weeks to observe the pathological changes of hepatic tissue, serum transaminase, serum lipid, fasting blood glucose, fasting insulin,liver lipid, lipid peroxidation indexes, and expression levels of TNF-a in liver.Outcome(1) General condition and pathomorphology change:The NAS score, body weight and liver index were increased in model group. Except body weight of YCHD, and liver index of gardenia and rhubarb group,NAS score of steatosis, lobular inflammation, ballooning in other treatment groups was reduced significantly. There was no significant difference among all treatment groups.(2) Serum transaminase:The level of serum ALT was reduced in gardenia, rhubarb and capllaris group, of serum AST was reduced in rhubarb group significantly. When medication and non-medication, the degree of the affection by all factors on ALT is gardenia> rhubarb>capi1laris, on AST was capillaris>rhubarb>gardenia, and all of the level in medica t ion was better than that in non-medication.There was interaction on ALT, AST in group of capillaris and rhubarb, interaction on AST in rhubarb and gardenia, capillar is and gardenia.(3) FBG and FINS:Rhubarb group and capillar is group could reduce the level of FINS and FBG significantly. The degree of the affection by all factors on FINS was capillaris> gardenia> rhubarb, on FBG was rhubarb> capillaris> gardenia, and all of the level in medication was better than that in non-medication. There was interaction on FINS,FBG in groups of capillaris and rhubarb, rhubarb and gardenia, interaction on FBG in capillaris and gardenia.(4) Lipid:The three herb groups could reduce serum TC, gardenia group and rhubarb group could reduce serum TG, LDL-C and TG in liver significantly. Rhubarb group also could increase HDL-C. The degree of the affection by all factors on serum TC, TG, and TG in liver was rhubarb>gardenia> capillaris, all of the level in medication was better than that in non-medication. On LDL-C was rhubarb> gardenia=capillaris, the level of rhubarb and gardenia in medicat ion was better than that in non-medication, the level of capillaris in non-medication was better than that in medication. On HDL-C was rhubarb=capillaris> gardenia, the level of it in rhubarb and capillaris group of medication was better than that of non-medication, the level of it in gardenia group of non-medication was better than that of medication. There was interaction on serum TC, TG, LDL-C and TG in liver in all combination groups.(5) Antioxidant and lipid peroxidation:The level of serum and liver MDA was lower significantly in the three herb groups. The degree of the affection by all factors on serum MDA was rhubarb>capillaris>gardenia, on liver MDA was capillaris>rhubarb>gardenia, all of the level in medicat ion was better than that in non-medication. Gardenia has the weakest affection on MDA among them. There was interaction on serum and liver MDA in all combination groups. The level of serum GSH-PX was increased significantly in the three herb groups. Also the level of it in liver was increased in capillaris and gardenia gourp. The degree of the affection by all factors on serum GSH-PX was gardenia>rhubarb>capillaris, all of the level in medication was better than that in non-medication. On liver GSH-PX was gardenia> capillaris>rhubarb, the level of it in gardenia and capillar is group of medicat ion was better than that of non-medicat ion, the level of it in rhubarb group of non-medication was better than that of medication. Gardenia has the greatest impact on GSH-PX among them. There was interaction on serum GSH-PX in capillaris and gardenia gourp, capillaris and rhubarb group.Also the interaction on liver GSH-PX in capillaris and rhubarb group.(6) Inflammation:The level of serum TNF-a was lower significantly in the three herb groups, the express ion levels of TNF-a in liver was lower in rhubarb group and gardenia gourp. The degree of the affection by all factors on serum TNF-a was gardenia=rhubarb>capillaris, all of the level in medication was better than that in non-medication. On TNF-a in liver was gardenia> rhubarb> capillaris. Gardenia had the greatest impact on TNF-a of all, and capillaris had the minimal impact. There was interaction on serum TNF-a in all combination groups. Also the interaction on liver TNF-a in capillaris and gardenia group.Conclusion(1) Rhubarb, capillaris and gardenia used alone had a significant effect on NASH,which role was similar but different emphases and had complementary also.The three herbs could treat NASH by regulating liver function, promoting lipid metabolism, inhibiting lipid peroxidation and inflammation, enhancing the antioxidant capacity. The efficacy of rhubarb on protecting the liver and regulating lipid was the best. On enhancing the antioxidant capacity, both capillaris and gardenia was better than rhubarb. Rhubarb, capillaris and gardenia has complementary in regulating model glucose and insulin levels. Rhubarb may has a more comprehensive treatment than capillaris and gardenia.(2) The three combinations of the herbs had interaction and complementary in many aspects of NASH. All of the them could affect liver function, lipid metabolism, lipid peroxidation and inflammation synergisticly. On enhanc ing the antioxidant capacity of liver, the combination of capillaris and rhubarb was the best. On reducing inflammation of liver, the combination of capillaris and gardenia was the best.(3) According to the comprehensive analysis of the results of the study, we could speculate that efficacy of YCHD may be not better than rhubarb on lipid-lower ing. Whi le on hepatoprotect ive, anti-inf lamination, inhibi t ion of lipid peroxidation and regulation of blood sugar and insulin, the whole prescription may be better than other single herbs or combinations. Whether the regulatory role of the antioxidant capacity in liver is better than each combination or not need to be confirmed. (4) The routine dose of YCHD used in clinical may be higher, safer and more effective than high-low dose. Demonstrated better efficacy trends of the traditional decoct ion compared wi th recipe granular formulat ions in the present s tudv. |
PDF Full Text Request