Regulatory effect of a Chinese herbal medicine formula on nonalcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a major cause of chronic liver disease.The Chinese herbal medicine(CHM)Dachaihu decoction(DCHD)has been proved to treat NAFLD with good efficacy in previous studies.Based on the TCM principle of formula formation,we divided DCHD into soothing liver part,invigorating spleen part,and dredging intestine part.Marshall officially proposed the concept of“intestinal-hepatic axis”,which systematically explains the interactions between the intestine and liver.We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine.Thus,we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model.AIM To investigate the effects of a CHM formula(a decoction of Chinese thorowax root,scutellaria root,and white peony root)on NAFLD and its regulatory effect on the“intestinal-liver”axis.METHODS Sixty rats were randomly divided into control,model,pioglitazone hydrochloride(PH),and CHM(a decoction of Chinese thorowax root,scutellaria root,and white peony root)groups.An NAFLD rat model was established using a high-fat highfructose diet for 16 wk.From the 13th week,rats were administered with PH or a decoction of Chinese thorowax,scutellaria,and white peony root(CHM group)for 4 wk.Rats in the control group and model group were administered with an equal volume of distilled water.At the end of the study,blood was collected via the abdominal aorta.Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin(HE)staining,Oil red O staining,and Masson staining.In addition,blood lipids,liver function markers,and triglyceride(TG)in liver tissues were analyzed.The levels of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),Toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-кB)in liver tissues and secreted immunoglobulin A(sIgA)in intestinal tissues were analyzed by ELISA,and protein and mRNA expression of occludin and zonula occludens-1(ZO-1)in the intestine were measured using Western blot and reverse transcriptionquantitative polymerase chain reaction,respectively.The endotoxin level in plasma was detected by endpoint chromogenic assay.RESULTS Compared to the normal control group,the liver coefficient,serum TG,total cholesterol(TC),low density lipoprotein(LDL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),blood glucose,plasma endotoxin,and the levels of TG,TNF-α,TGF-β,NF-kB,and TLR4 in liver tissues increased significantly in the model group,while serum high density lipoprotein(HDL),intestinal sIgA,and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group(P<0.01).PH and CHM attenuated the elevated liver coefficient,serum TG,TC,LDL,AST,and ALT,blood glucose,plasma endotoxin,and the levels of TG,TNF-α,TGF-β,NF-kB,and TLR4 in liver tissues and increased serum HDL levels compared to the model group(P<0.01).Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups(P<0.01).CONCLUSION The decoction of Chinese thorowax root,scutellaria root,and white peony root is beneficial in regulating lipid metabolism and liver function,which indicates that it has a good effect on the liver.To a certain extent,this CHM formula can affect both the liver and intestine,while its effect on the liver is superior to that on the intestine.

Effects of stress of different duration on depression-like behavior and expression of CB1 and GluA1 in medial prefrontal cortex of rats

Objective:To explore the changes of cannabinoid receptor(CB1)and AMPA receptor subunit GluA1 in the medial prefrontal cortex(mPFC)of depression model rats induced by chronic unpredictable mild stress(CUMS).Methods:30 rats were randomly divided into three groups.The three-week model group was given a three-week CUMS model,the four-week model group was given a four-week CUMS model,and the control group was given no treatment.The behavior of rats were detected in each group,and the expression of CB1 and GluA1 protein in synaptosomes in mPFC brain region was detected by Western blot.Results:Compared with the control group,the surcose preference decreased,the feeding latency increased in the novel inhibition feeding test,and the immobility time increased in the forced swimming test in the four-week model group.However,after three weeks of CUMS,there was no obvious change in the behavior of rats compared with the control group,suggesting that four-week model of CUMS was successful.CUMS can reduce the expression level of CB1 and GluA1 protein in synaptosomes of mPFC brain area in four-week model group(P<0.05),but there was no significant difference between three-week model group and control group.Conclusion:Four-week CUMS was more likely to lead to depressive-like behavior in rats,which may be closely related to the expression of CB1 and GluA1 in mPFC.

Effects of Dachaihu Decoction and Its “Prescription Elements” on Intestinal Flora of Nonalcoholic Fatty Liver Disease Model Rats

Objective:The study objective was to observe the effect of Dachaihu decoction and its "prescription elements" on intestinal flora of model rats with nonalcoholic fatty liver disease (NAFLD). Materials and Methods:Healthy male Sprague-Dawley rats were randomly divided into the following seven groups (n=105):normal, model, pioglitazone hydrochloride (PH), Shuganlidan, Jianpihuatan, Tongfuxiezhuo, and dachaihu decoction (DD). 16SrRNA high-throughput IIlumina sequencing platform was used for sequencing, and bioinformatics analysis of rat intestinal flora was done. Results:Compared with the normal group, rats in the model, PH, Shuganlidan, Jianpihuatan, Tongfuxiezhuo,and DD groups showed significant differences in the intestinal microflora structure. The microorganisms that play an important role in the normal group are Ruminococcaceae, Oscillospira, Lactobacillales, Lactobacillaceae, Lactobacillus, bacilli, Ruminococcus, TM7, Spirochaetes,Clostridium, Elusimicrobia, Elusimicrobiaceae, Elusimicrobiales, Lactobacillus helveticus, Lactobacillus reuteri, Elusimicrobium, RF39, and Christensenellaceae;in the model group are Ruminococcus gnavus;in the PH group are Prevotella, Paraprevotellaceae, and Blautia;in the Jianpihuatan group are Bacteroidetes, Bacteroidia, Bacteroidales, Roseburia, Rikenellaceae, and?Stridium methylpentosum;in the TongfuXiezhuo group are Bacteroidaceae, Bacteroides, Porphyromonadaceae, Parabacteroide, 4C0d2, Cyanobacteria, YS2, Parabacteroides distasonis,Bacteroides uniformis, Verrucomicrobiaceae, Verrucomicrobiae, Verrucomicrobiales, Akkermansia, Akkermansia muciniphila, Coprobacillus,Parabacteroides gordonii, Blautia producta, and Ruminococcus torques;and in the DD group are Erysipelotrichales, Erysipelotrichi, and Erysipelothrichaceae. Conclusion:The Tongfuxiezhuo prescription elements of the DD significantly improved the intestinal flora of rats with NAFLD, improving the relative abundance of beneficial bacteria in the intestinal flora of NAFLD rats such as Bacteroides, Sartre genus,Vibrio pseudobutyrate bacteria, and Akkermansia muciniphila. This subsequently improved the glucose and lipid metabolism in NAFLD rats,reducing fat deposition in the liver, inhibiting intestinal inflammatory reaction, and maintaining the integrity of intestinal mucosal barrier. The action target is the intestinal axis of "intestinal–hepatic axis."