| Diabetes mellitus(DM)is a systemic metabolic disease characterized by increased level of blood glucose,resulting from insufficient insulin secretion or insulin resistance and/or combination of both.As reported,DM has become a worldwide disease,the global incidence rate of DM has reached 9%(415 million),and the potential morbidity population is 318million;among which type 2 diabete mellitus(T2DM)is the most common,accounting for more than 90%of DM patients.The high prevalence and long-term hyperglycemia status of diabetic may cause a series of complications,which seriously endangers the health of the body and brings a large medical burden to patients and society.At present,more than 60%of patients still cannot be remedied effectively.What is worse is that the traditional hypoglycemic drugs have been exposed its severe liver and kidney damage as well as drug resistance.Therefore,it is still urgent for the development of for T2DM therapeutic drug.Unlike the embarrassment of single-target hypoglycemic drugs,the traditional Chinese medicine with its multi-ingredient,multi-target and multi-function property has accumulated a wealth of experience in diabetes treatment,and drugs development based on traditional medicines has become a research hotspot.QianJin HuangLianWan(HLW)is a prescription of traditional Chinese medicine recorded in the book‘‘Qian-Jin-Yao-Fang''by Si-Miao Sun,including two hrebs Rhizoma coptidis(HuangLian)and Radix Rehmanniae(DiHuang),among which HuangLian is monarch drug,DiHuang is adjuvant drug.The prescription is used to treat“Xiao Ke”with the effect of nourishing yin and clearing heat,and its curative effect has been validated by clinic and anmimal experiments.The only shortcoming is that,most of the current research on HLW did not completely adhere to the original conception of the prescription;especially that dry Dihuang detection was always used in modern preparing instead of fresh Dihuang juice used in traditional ways,thus it is needed to further explore whether this change will cause the efficacy damnify or modify of the original prescription.Therefore,this study is carried out to investigate the efficacy and mechanism of HLW in the context of traditional application and to further clarify the following question:(1)Whether the efficacy will make a difference when using dry DiHuang dection instead of fresh DiHuang juice in the preparation of HLW?(2)Does the the different ratios(1:3 and 1:10)of Huanglian and DiHuang recorded in original HLW prescription will cause different therapeutic effects?(3)Will the effects of HuangLian,DiHuang and their active ingredients be different when used alone or in combination,and what is the primary medicinal composition?In order to clarify the efficacy and mechanism of HLW on regulating glycolipid metabolism and relieving insulin resistance;and further to discover the optimal raw material,proportion,preparing process,and the primary effective substance of HLW.The comparative studies were designed as following:(1)Comparative study on the efficacy of different doses of HLW,including normal control group(NC),model group(MX),metformin group(MF),HuangLianWan low low dose group(HLW-LL),HuangLianWan low dose group(HLW-L),HuangLianWan medium dose group(HLW-M),HuangLianWan high dose group(HLW-H);(2)Comparative study on the efficacy of different preparation methods of HLW,including NC,MX,HLW-M,HuangLianWan freeze-dried powder group(HLW-DG),HuangLian:DiHuang 1:3 fried baking powder group(HLW-JH),HuangLian:DiHuang 1:3decoction group(H:S-1:3JY),HuangLian:DiHuang 1:10 decoction group(H:S-1:10JY);(3)Comparative study on the efficacy of single used HuangLian and DiHuang,including NC,MX,HLW-M,fresh Dihuang juice group(DHZ),dry Dihuang group(SDH),HuangLian group(HL);(4)Comparative study on the efficacy of HLW and their active ingredients,including NC,MX,HLW-M,berberine group(XBJ),catalpol group(ZC),berberine+catalpol group(X+Z).In this experiment,the T2DM rat model was induced by a high-fat diet with a small-dose streptozotocin(STZ).At the end of the experiment,we found that compared with the MX,MF,HLW-M,HLW-H,HLW-JH,H:S-1:10JY,HL and ZC could significantly reduce the Fasting blood glucose of T2DM rats.The blood sugar value of HLW-M and HLW-H was faster than that of MF.The results of oral glucose tolerance test showed that compared with MX,the AUC values of T2DM rats were significantly decreased in HLW-M,HLW-H,HLW-JH,DHZ,SDH,HL and X+Z,suggesting that the medium and high doses of HLW could significantly improve the impaired glucose tolerance of T2DM rats,and the effect was better than MF.The results of four blood lipids(TG,TC,LDL-C and HDL-C)showed that compared with MX,all groups could significantly improve the abnormal blood lipids in T2DM rats,suggesting that HLW could significantly regulate blood lipids to near normal levels,and its effect was similar to MF.The results of serum insulin level,insulin resistance index and insulin sensitivity index indicated that compared with MX,HLW-H,HLW-JH and HL could significantly reduce serum insulin level,reduce insulin resistance and enhance insulin sensitivity.The results of SOD and MDA showed that,compared with MX,except for HLW-LL,the other groups could significantly improve the oxidative stress state of T2DM rats.ALT and AST results showed that compared with MX,except for HLW-JH,DHZ,HL and X+C,the liver function of rats in other groups was significantly improved.The results of pathological sections of liver and pancreas showed that the medium and high doses of HLW had the best protective effect on liver and pancreas.The results of cyclic nucleotides showed that HLW-M and HLW-H could significantly improve the Yin deficiency status of T2DM rats,and the effect was better than MF.The results of Na~+-K~+-ATPase activity detection showed that compared with MX,each administration group could significantly reduce the activity of Na~+-K~+-ATPase in T2DM rats.The results show that,HLW has a definite curative effect on T2DM,which can significantly improve glucose and lipid metabolism in T2DM rats and HLW has a dose-dependent relationship;HLW can significantly improve the typical symptoms(polyuria,polydipsia,polyphagia,weight loss)of T2DM rats;it can significantly reduce insulin content and insulin resistance index,and improve insulin resistance;it can significantly reduce liver index;it can improve the antioxidant stress ability of T2DM rats by increasing SOD activity and decreasing MDA content;it can improve the liver function and Yin deficiency state of T2DM rats;it can reduce the damage of pancreatic?cells and pathological changes in liver and pancreas,and play a protective role in liver and pancreas tissue in T2DM rats.From the point of view of drug raw materials,prescription ratio and preparation method,the mortality rate of T2DM rats was low and FBG was stable after HLW intervention;after the prognosis of HL and H:S 1:3,though the FBG in T2DM rats decreased to a very low level,the risk of death was very high;the effect of HLW freeze-dried powder is not good,and the possible reason maybe that under directly freeze-dried preparation method of freeze-dried powder of HLW,there was no enough time for HuangLian and fresh DiHuang juice to absord and react with each other;the possible active ingredients in HLW and the compatibility of HuangLian and DiHuang have certain curative effect on each index,but the effect is not as good as HLW.In summary,HLW made from fresh DiHuang juice has better curative effect.This study provides a scientific reference for the therapeutic effect of HLW on T2DM. |
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