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 da...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.展开更多
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, ...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.展开更多
Objective:To observe the effect and mechanism of Xiangsha Liujunzi decoction(XSLJZD)drug serum on gastric antrum smooth muscle cells(SMCs)in rats with functional dyspepsia(FD).Methods:Gastric antrum SMCs from rats wit...Objective:To observe the effect and mechanism of Xiangsha Liujunzi decoction(XSLJZD)drug serum on gastric antrum smooth muscle cells(SMCs)in rats with functional dyspepsia(FD).Methods:Gastric antrum SMCs from rats with FD were isolated,cultured,and then divided into six groups as follows:control,model,domperidone,low-dose XSLJZD(LXSLJZD),medium-dose XSLJZD(MXSLJZD),and high-dose XSLJZD(HXSLJZD).Each group was administered the corresponding drug serum for intervention.Drug serum intervention conditions and proliferative activity of SMCs were tested by cholecystokinin octapeptide.Ghrelin,gastrin,somatostatin,and substance P(SP)levels were measured by ELISA.Somatostatin and SP mRNA expression was measured by real-time PCR.Results:A concentration of 10%drug serum for 24 h was decided to be the best intervention condition for later study.The mean optical density value in the model group was lower than that in the control group(P紏.001).Optical density values in the domperidone and HXSLJZD groups were higher than those in the model group(P?.025,P?.032,respectively).Gastrin,SP,and ghrelin levels in the model group were lower(P?.007,P?.037,P?.005,respectively),but somatostatin levels were higher,compared with those in the control group(P?.031).Gastrin,SP,and ghrelin levels in the domperidone,MXSLJZD,and HXSLJZD groups were higher than those in the model group(all P<.05).Somatostatin levels in the four drug-treated groups were lower than those in the model group(P?.002,P?.007,P?.001,P?.009,respectively).SP mRNA levels in the model group were lower than those in the control,domperidone,MXSLJZD,and HXSLJZD groups(P?.037 P?.016,P?.025,P?.002,respectively).Somatostatin mRNA levels in the model group were higher than those in the control and MXSLJZD groups(P紏.042,P紏.035).Conclusions:XSLJZD and domperidone drug serum effectively promote proliferative activity of gastric antrum SMCs in an FD model.The mechanism of this activity may be regulated by gastrointestinal hormones.展开更多
Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula kno...Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula known as Dachaihu Decoction(DD)on NAFLD.Methods:Sixty rats were randomized into four groups:control,model,pioglitazone hydrochloride(PH)and DD in equal.NAFLD was produced via administration of a high-fat high-sugar diet for 16 weeks in all but the control group.From the 13th week,a solution of PH or DD prepared with water was delivered via intragastric administration to the PH and DD groups;the remaining two groups received an equivalent volume of distilled water.Twelve hours from the last administration,we selected eight rats from each group in random.After anesthetization,the abdominal aorta blood and liver tissues were collected.The morphological changes were observed and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),fasting plasma glucose(FBG),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-κB)were tested.Results:Compared with the control group,the levels of serum ALT,AST,TC,TG,LDL-C and FBG,and TGF-β1,TNF-α,TLR4,NF-κB in the model group all showed significant increases(P<.01).Compared with the model group,these same indicators in the PH and DD groups all showed remarkable decreases(P<.05).Conclusion:The efficacy of DD in NAFLD rats was shown to be effectively equivalent to that of PH,with demonstrated effects of DD that included reductions in hepatic steatosis and serum and hepatic lipid levels,and lowered blood glucose levels.We deduce that DD has an inhibitory effect on NAFLD induced by a high-fat high-sugar diet in rats.展开更多
OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cispla...OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.展开更多
This paper mainly describes the experiences of clinical application of Dachaihu Decoction in treating chronic pelvic infection, coronary heart disease, insomnia, and hepatolithiasis.
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 w...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.展开更多
OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene ...OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene expression profile of peripheral blood mononuclear cells(PBMCs)from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy.METHODS:The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database.Differentially expressed genes(DEGs)were screened by paired sample t-test and the multiple ratio method.Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses were performed using the DAVID database.The protein–protein interaction(PPI)network was constructed using interaction gene library retrieval tools and Cytoscape software.RESULTS:A total of 162 DEGs were identified,with 67 upregulated genes and 95 downregulated genes.The functional distribution of Gene Oncology(GO)genes showed that DEGs were mostly concentrated in extracellular regions,calcium ion binding,and transcriptase activity.KEGG pathway analysis showed that cytokine–cytokine receptor interactions were significantly enriched.PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree:IL2,PIWIL4,DICER1,PIWIL2,SAA1,XCL1,IL22RA1,ARHGAP11A,DCP1A,and GDNF.Among them,the central protein-coding gene with the highest node degree was IL2.In addition,the central protein-coding genes with high node degrees and high molecular complex detection(MCODE)scores were PIWIL4,DICER1,PIWIL2,and DCP1A,all of which are related to tumor development.CONCLUSIONS:One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data.IL2,PIWIL4,DICER1,PIWIL2,and DCP1 A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC.Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.展开更多
基金the National Science Foundation of China(No.81773997)Key Research and Development Project of Shandong Province(No.2016ZDJS07A21 and 2017CXGC1301)Special Fund of Taishan Scholars Project(No.ts201511107).
文摘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.
基金Supported by the National Natural Science Foundation of China,No.81673816the Key Basic Research Project of Shaanxi Province,No.2017ZDJC-14the Key Research Program of Natural Science of Shaanxi Education Department,No.15JS027
文摘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.
基金We are grateful for the technical support provided by Dr.Lin Lv and Dr.FengyunWang(Xiyuan Hospital,affiliated with the Chinese Academy of TCM,Beijing,China)and Xin Ma(Beijing University of Chinese Medicine,Beijing,China).
文摘Objective:To observe the effect and mechanism of Xiangsha Liujunzi decoction(XSLJZD)drug serum on gastric antrum smooth muscle cells(SMCs)in rats with functional dyspepsia(FD).Methods:Gastric antrum SMCs from rats with FD were isolated,cultured,and then divided into six groups as follows:control,model,domperidone,low-dose XSLJZD(LXSLJZD),medium-dose XSLJZD(MXSLJZD),and high-dose XSLJZD(HXSLJZD).Each group was administered the corresponding drug serum for intervention.Drug serum intervention conditions and proliferative activity of SMCs were tested by cholecystokinin octapeptide.Ghrelin,gastrin,somatostatin,and substance P(SP)levels were measured by ELISA.Somatostatin and SP mRNA expression was measured by real-time PCR.Results:A concentration of 10%drug serum for 24 h was decided to be the best intervention condition for later study.The mean optical density value in the model group was lower than that in the control group(P紏.001).Optical density values in the domperidone and HXSLJZD groups were higher than those in the model group(P?.025,P?.032,respectively).Gastrin,SP,and ghrelin levels in the model group were lower(P?.007,P?.037,P?.005,respectively),but somatostatin levels were higher,compared with those in the control group(P?.031).Gastrin,SP,and ghrelin levels in the domperidone,MXSLJZD,and HXSLJZD groups were higher than those in the model group(all P<.05).Somatostatin levels in the four drug-treated groups were lower than those in the model group(P?.002,P?.007,P?.001,P?.009,respectively).SP mRNA levels in the model group were lower than those in the control,domperidone,MXSLJZD,and HXSLJZD groups(P?.037 P?.016,P?.025,P?.002,respectively).Somatostatin mRNA levels in the model group were higher than those in the control and MXSLJZD groups(P紏.042,P紏.035).Conclusions:XSLJZD and domperidone drug serum effectively promote proliferative activity of gastric antrum SMCs in an FD model.The mechanism of this activity may be regulated by gastrointestinal hormones.
基金supported by the National Natural Science Foundation of China(81673868).
文摘Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula known as Dachaihu Decoction(DD)on NAFLD.Methods:Sixty rats were randomized into four groups:control,model,pioglitazone hydrochloride(PH)and DD in equal.NAFLD was produced via administration of a high-fat high-sugar diet for 16 weeks in all but the control group.From the 13th week,a solution of PH or DD prepared with water was delivered via intragastric administration to the PH and DD groups;the remaining two groups received an equivalent volume of distilled water.Twelve hours from the last administration,we selected eight rats from each group in random.After anesthetization,the abdominal aorta blood and liver tissues were collected.The morphological changes were observed and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),fasting plasma glucose(FBG),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-κB)were tested.Results:Compared with the control group,the levels of serum ALT,AST,TC,TG,LDL-C and FBG,and TGF-β1,TNF-α,TLR4,NF-κB in the model group all showed significant increases(P<.01).Compared with the model group,these same indicators in the PH and DD groups all showed remarkable decreases(P<.05).Conclusion:The efficacy of DD in NAFLD rats was shown to be effectively equivalent to that of PH,with demonstrated effects of DD that included reductions in hepatic steatosis and serum and hepatic lipid levels,and lowered blood glucose levels.We deduce that DD has an inhibitory effect on NAFLD induced by a high-fat high-sugar diet in rats.
基金National Natural Science Foundation of China(82174143)and Scientific Research Foundation of Guangdong Pharmaceutical University(51348136)。
文摘OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.
文摘This paper mainly describes the experiences of clinical application of Dachaihu Decoction in treating chronic pelvic infection, coronary heart disease, insomnia, and hepatolithiasis.
基金supported by grants from the National Natural Science Foundation of China(No.82003641)the Beijing Natural Science Foundation(No.7222147).
文摘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.
基金Supported by the National Natural Science Foundation of China(NSFC)(81903270)(Therapeutic Effect and Mechanism of Embryonic Lung Progenitor Cell Transplantation on Silicosis Fibrosis)and(81703987)(Study on the Synergistic Effect and Mechanism of Yiqi Yangyin Jiedu Prescription Combined with Anti-CTLA-4 Mab in Inducing Anti-Lung Cancer Immune Response)Jinan Science and Technology Project(201907019)(Study of Therapy and Mechanisms of Embryonic Lung Stem Cell Transplantation on Silicosis Fibrosis)+4 种基金the Shanghai Science and Technology Commission(19401971200)(a Multicenter Randomized Controlled Study on Improving Prognosis of Patients With StageⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang's Prescription for Qi-Yin Differentiation and Treatment)the Emerging Frontier Technology Joint Research Project of Shanghai Shenkang Hospital Development Center(SHDC12018131)(a Multicenter Randomized Controlled Double-Blind Study on the Prevention and Treatment of Postoperative Recurrence and Metastasis Of StageⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang Qi-Yin Differentiation Method)the Major Project of Scientific Research and Innovation Plan of Shanghai Education Commission(No.2017-01-07-00-10-E00064)(Study on the Mechanism of Feyanning Prescription Against Lung Cancer Growth and Metastasis Derived from Jingqi Theory)Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine(AJ-37)(Clinical Study of Yiqi Yangyin Jiedu Prescription Combined With Oxitinib in the Treatment of Advanced Lung Cancer With T790M Mutation)and(AJ-41)(Clinical Study of“Decubitus Chiropractic Therapy”in the Treatment of Vertebral Artery Type Cervical Spondylosis)National Traditional Chinese Medicine Clinical Research Base Long-Yi-Xue-Zhe Nurturing Plan(LYTD-64)(Mechanism of Reversal of EGFR-Tkis Resistance Induced By HGF in Tumor-Bearing H1975-SCID Mice Based on Huachansu Injection)。
文摘OBJECTIVE:To further clarify the anticancer mechanisms of Liujunzi decoction(六君子汤)and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer(NSCLC)by re-analyzing differential gene expression profile of peripheral blood mononuclear cells(PBMCs)from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy.METHODS:The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database.Differentially expressed genes(DEGs)were screened by paired sample t-test and the multiple ratio method.Gene ontology and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses were performed using the DAVID database.The protein–protein interaction(PPI)network was constructed using interaction gene library retrieval tools and Cytoscape software.RESULTS:A total of 162 DEGs were identified,with 67 upregulated genes and 95 downregulated genes.The functional distribution of Gene Oncology(GO)genes showed that DEGs were mostly concentrated in extracellular regions,calcium ion binding,and transcriptase activity.KEGG pathway analysis showed that cytokine–cytokine receptor interactions were significantly enriched.PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree:IL2,PIWIL4,DICER1,PIWIL2,SAA1,XCL1,IL22RA1,ARHGAP11A,DCP1A,and GDNF.Among them,the central protein-coding gene with the highest node degree was IL2.In addition,the central protein-coding genes with high node degrees and high molecular complex detection(MCODE)scores were PIWIL4,DICER1,PIWIL2,and DCP1A,all of which are related to tumor development.CONCLUSIONS:One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data.IL2,PIWIL4,DICER1,PIWIL2,and DCP1 A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC.Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.