Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis

AIM To explore the role of macrophages in chronic pancreatitis(CP) and the effect of Dachaihu decoction(DCHD) on pancreatic fibrosis in mice.METHODS Kun Ming mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine(3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6(IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1(MCP-1), macrophage inflammatory protein-1α(MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α m RNA, and fibronectin levels were reduced. CONCLUSION The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

A Meta-analysis of Dachaihu Decoction combined with western medicine in the treatment of acute pancreatitis with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat

Backgroud:To evaluate the clinical efficacy and safety of Dachaihu Decoction in the treatment of acute pancreatitis(AP)with the traditional Chinese medicine(TCM)syndrome of liver qi depression and liver-gallbladder dampness-heat.Methods:We searched randomized controlled trials of Dachaihu Decoction in the treatment of AP with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat from databases in CNKI,WanFang,VIP,Embase,PubMed,and Cochrane Library(from established to August 2019).All the retrieved documents were imported into the Noteexpress software for screening and management,and the included documents were evaluated for quality and data extracted.Statistical analysis was performed with RevMan(version 5.3).Results:A total of 132 articles were retrieved and 8 studies were included to analysis,including 679 patients.Quality evaluation of included studies suggested that the quality of the literatures is generally not high.Meta-analysis showed that the total clinical effective rate of AP was higher in the treatment group than in the control group[OR=5.00,95%CI(2.86,8.73)],and the difference was statistically significant(P<0.00001).The patient's abdominal pain relief time[MD=-0.57,95%CI(-0.86,-0.27),P=0.0002],bloating relief time[MD=-0.71,95%CI(-1.05,-0.37),P=0.04],time of serum amylase returning to normal[MD=-1.00,95%CI(-1.60,-0.40),P=0.001]and time of urinary amylase returning to normal[MD=-1.62,95%CI(-2.88,-0.37),P=0.01]all lower than the control group.But there was no statistically significant difference between the treatment group and the control group at the first defecation time[MD=-0.86,95%CI(-1.75,-0.03),P=0.06].The patient's serum TNF-a levels on the 3rd[MD=-28.53,95%CI(-49.57,-7.49),P=0.008]and 7th day[MD=-26.13,95%CI(-49.76,-2.50),P=0.03]in the treatment group were statistically lower in the treatment group than in the control group.Similarly,the patient's serum IL-6 levels on the 3rd[MD=-6.62,95%CI(-12.49,-0.75),P=0.03]and 7th day[MD=-11.98,95%CI(-22.25,-1.71),P=0.02]were also statistically lower in the treatment group than in the control group.No serious complications or adverse reactions were observed.Conclusion:Dachaihu Decoction combined with western medicine in the treatment of AP with the TCM syndrome of liver qi depression and liver-gallbladder dampness-heat can improve clinical efficacy compared with western medicine alone.In addition,the combination therapy method is safe and can be used for syndrome differentiation of AP patients in the clinic.

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."

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier

Background:Colorectal cancer(CRC)is the third most common malignancy and the second deadliest cancer worldwide.Metastasis to the liver,the most common metastatic site in CRC,is the leading cause of death in patients with CRC.Hyperlipidemia,which is common in patients with CRC,promotes CRC progression and metastasis.Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition.The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear,and there is an unmet need for effective and low-cost treatments for patients with CRC.Methods:A mouse cecum orthotopic CRC model combined with high-fat diet(HFD)feeding,was established to mimic liver metastasis in CRC in obese patients.The effects of Dachaihu decoction(DCHD),a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease,and of the conventional prescription medicine obeticholic acid(OCA)were evaluated.HFD-induced obesity,hyperlipidemia,and CRC liver metastasis were assessed,along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues.The effects of DCHD and OCA on HFD-induced outcomes were evaluated,and human umbilical vein endothelial cells(HUVECs)treated with bile acids(BAs)and DCHD were used to study the underlying mechanisms in vitro.Results:HFD-mediated obesity and hyperlipidemia promoted CRC metastasis,accompanied by disruption of the gut vascular barrier(GVB)and altered bile acid(BA)metabolism.DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC,improving overall survival.Those effects of DCHD were equivalent to or better than those of OCA.DCHD regulated the expression of genes of BA metabolism and tight junctions(TJ)to prevent HFDinduced disruption of the GVB.In HUVECs,DCHD prevented the increases in intracellular Ca2t and accumulation of reactive oxygen species induced by primary conjugated BAs,assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins,thereby maintaining the integrity of the endothelial barrier.Conclusions:The data provide a link between hypernutrition and GVB disruption,which contributes to high liver metastasis in patients with CRC.DCHD may represent a novel therapy in CRC,and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.