Protective Effect And Mechanism Of Veratrilla Baillonii Franch On Liver Injury

The liver has the functions of secreting bile,decomposing sugar and storing glycogen.It is the largest digestive gland in the human body.Due to the strong compensatory function of the liver and the difficult discovery of early liver injury,liver injury is not easy to attract people’s attention.There is a lack of specific drugs to prevent and treat liver injury,since the present medicine is easy to produce toxic and side effects.Therefore,searching for traditional drugs to treat liver injury and explore its multi-target and multi-channel mechanism have attracted more and more attention.Veratrilla baillonill Franch,also known as Yunnan Scutellaria,Lijiang Jinbuhuan,Sophora flavescens,huang longdan,etc.In ethnic minority areas,it is commonly used to treat diseases caused by heat toxin such as lung heat cough,acute and chronic gastritis,enteritis,chronic cholecystitis,icteric hepatitis,carbuncle and sore swelling toxin and so on.Based on our previous studies,animal models were constructed to observe the hepatoprotective effect of Veratrilla baillonill Franch against diabetic liver injury and cholestatic liver injury(CHI)and to explore its potential mechanism.The following studies were carried out in this study:(1)Protective effect and mechanism of water extract of Veratrilla baillonill Franch(WVBF)on T2DM model rats.T2DM rat model was established by high sugar and high fat diet combined with injection of low-dose streptozotocin(HFD-STZ).The results showed that WVBF could improve the general state,body weight,liver coefficient,fasting blood glucose,glucose tolerance,serum insulin,liver function and biochemical indexes of T2DM rats,and could ameliorate the pathological damage of liver,kidney,pancreas and fat.In addition,it could also regulate oxidative stress and inflammatory response,and activate liver IRS1/PI3K/AKT signal pathway.These results suggest that WVBF can alleviate liver injury in T2DM rats by inhibit oxidative stress,inflammatory response and insulin resistance.(2)Transcriptome analysis on the liver of T2DM rats treated with WVBF.Transcriptional sequencing on the liver of diabetic rats after WVBF treatment was carried out to explore the therapeutic effect and mechanism of WVBF on liver injury.The total RNA was extracted from fresh rat liver samples,and the database was built and sequenced after purification and quality inspection.Sequencing analysis showed that 643 deferentially expressed genes(DEG)were found between MC and NC group,and 381 DEG were detected between WVBF(25 mg/kg)group and MC group.In the KEGG enrichment analysis of WVBF(25 mg/kg)group and MC group,DEG were mainly enriched in insulin and inflammatory response(insulin signaling pathway,FOXO signaling pathway,AMPK signaling pathway),and DEG(c-Met,Irs1 and G6pc)were enriched in KEGG pathway.In order to verify the regulatory effect of WVBF on insulin resistance related genes,key molecules related to insulin signal transduction and glycolysis/gluconeogenesis(Pik3r1,AKT1,Fox O1 and SIRT1)were selected,and the mRNA levels of the above seven genes were verified by qRT-PCR.The results showed that WVBF treatment could inhibit the mRNA levels of Foxo1,G6 pc,c-Met and Pik3r1 in liver;The expression of genes related to metabolism and inflammation,including Sirt1,Irs1 and Akt1,increased significantly after WVBF treatment.These results suggest that WVBF can protect against liver injury by regulating insulin resistance signaling pathway.(3)Protective effect and mechanism of WVBF on ANIT induced CHI in mice.CHI mouse model was induced by ANIT.The results showed that WVBF could improve the general state and liver coefficient of C57BL/6 male mice,regulate the abnormalities of biochemical indexes of liver and gallbladder,and ameliorate the pathological injury of liver.In addition.WVBF could affect the bile acid metabolic pathway which FXR is the central target,regulate the mRNA levels of Fxr,Shp,Bsep,Ntcp and Mpr2.The above results suggest that WVBF protects against ANIT induced cholestatic liver injury by affecting the metabolism,secretion,transport and re-absorption of bile acids,and its mechanism may be related to the regulation of FXR/SHP signaling pathway.To sum up,this study found that WVBF has a good effect of lowering blood sugar and liver protection,and it can treat diabetic liver injury and CHI through different signal pathways,which fully embodies pharmacodynamic advantage of Veratrilla baillonill Franch with multiple components,multiple targets and multiple pathways.It provides a scientific basis for its research and application in the treatment of T2DM liver injury and cholestasis.