Danggui Buxue decoction promotes proliferation and differentiation of Caco-2 cells and antagonizes obesity by stimulating apolipoprotein-IV expression

Background:Chinese medicine has been proposed as a novel approach to the prevention of metabolic disorders such as obesity.Danggui Buxue decoction,a decoction prepared from Huangqi(Astragali Radix)and Danggui(Angelicae Sinensis Radix),has been used to nourish vitality and enhance blood circulation in traditional Chinese medicine.However,the effect of Danggui Buxue decoction on obesity is still primarily unknown.Methods:Cell proliferation,differentiation,and apolipoprotein-IV transcription were investigated to explore the function of Danggui Buxue decoction by methyl thiazolyl tetrazolium assay,alkaline phosphatase assay,and luciferase assay,respectively.Results:Danggui Buxue decoction promoted cell growth by up to 15%(P=0.034)and induced cell differentiation by up to 38%(P=0.006)at 0.3 mg/mL.Moreover,Danggui Buxue decoction enhanced the transcription of apolipoprotein-IV by 2.4 times(P=0.027),activating its promoter by 28.9%(P=0.031)at 0.3 mg/mL.In addition,Danggui Buxue decoction functioned in a dose-dependent manner.Conclusion:These results suggest that Danggui Buxue decoction promotes cell differentiation by enhancing apolipoprotein-IV transcription and alkaline phosphatase activity,and it may also have a potential anti-obesity effect because apolipoprotein-IV transcription is closely related to the reduction of food intake.

Dissecting the underlying pharmaceutical mechanism of Danggui Buxue decoction acting on idiopathic pulmonary fibrosis with network pharmacology

Backgroud:Danggui Buxue decoction(DBD),a classical prescription in traditional Chinese medicine,has been found to have protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis.However,the biological activity of individual chemical components and mechanism of action of whole formula are not clear.Methods:Potential targets of active ingredients of DBD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SymMap database.Target genes related to idiopathic pulmonary fibrosis were obtained from the Online Mendelian Inheritance in Man database,Therapeutic Targets Database and Gkb database.Then,the common targets were obtained by overlapping the potential targets of active ingredients in DBD and diseases related targets.The selected targets were subjected to Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology analysis,and the network map of active component-target-pathway was established using Cytoscape 3.7.1 software.The active components of DBD with most targets were selected for fibrosis-related marker verification.The mRNA and protein expression of fibrosis markers,α-smooth muscle actin,collagen 1 and fibronectin,were detected in TGF-β1-induced fibroblast cell line after treatment with the active components.Results:The 14 active ingredients,such as quercetin and kaempferol,were screened from DBD.It acts on 26 targets like estrogen receptor 2 and prostaglandin-endoperoxide synthase 2,and mainly involves 38 signaling pathways such as cell inflammation and autophagy.Kaempferol and quercetin are the two compounds with the highest network regulation,which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markersα-smooth muscle actin,collagen 1 and fibronectin.Conclusion:The integration mode of multi-component,multi-target,multi-channel and mechanism of DBD in the treatment of idiopathic pulmonary fibrosis are predicted by means of network pharmacology.Our study could indicate the direction of further anti-fibrotic mechanism research.

Potential Mechanism of Danggui Buxue Decoction in Treating Iron Deficiency Anemia Based on Network Pharmacology and Molecular Docking Technology

[Objectives]To explore the potential mechanism of Danggui Buxue Decoction in treating the iron deficiency anemia(IDA)based on network pharmacology and molecular docking technology.[Methods]The active components and target proteins of Danggui Buxue Decoction were searched in databases such as TCMSP,OMIM,GeneCards,Drugbank,String,Metascape,etc.,and the target proteins shared with IDA were screened out,and the information about the signal pathways and biological functions of these target proteins was obtained.[Results]17 active components of Danggui Buxue Decoction and 24 potential targets for the treatment of IDA were obtained.With the aid of String database and Cytoscape software,the protein interaction network was obtained and the network topology analysis was performed.Four potential core targets with higher scores were obtained,namely F2,NOS2,NOS3,and PPARG.Using the Metascape database,GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the potential targets of Danggui Buxue Decoction in the treatment of IDA,and the important biological processes,cell composition,molecular functions and signal pathways related to the target were screened through the R language.The results show that biological processes are related to positive regulation of growth,cell composition is related to membrane microdomain,and molecular functions are related to oxidoreductase activity.The signal pathways involved are mainly AGE-RAGE signal pathway,TNF signal pathway and IL-17 signal pathway.Finally,the molecular docking results confirmed that the active components of Danggui Buxue Decoction have a good binding ability with the target.[Conclusions]Danggui Buxue Decoction treats the IDA through multiple components,multiple targets,multiple signal pathways,and multiple biological functions.

Study on the Molecular Mechanism of Danggui Buxue Decoction in Intervention of Perimenopausal Syndrome Based on Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.

Exploring the mechanism of Danggui Buxue Decoction in treating osteoporosis from vitamin D-axis

Osteoporosis is a common disease in the middle-aged and elderly population and is a global health problem that needs to be solved urgently.Vitamin D deficiency is closely related to osteoporosis,and it is of practical significance to prevent and treat kidney and strengthen bone therapy.A large number of literature have confirmed that qi and blood to represent Danggui Buxue Decoction has a reliable therapeutic effect on osteoporosis,but the mechanism is still unclear.Based on the previous work of the research group,it is believed that the vitamin D axis may be a potential target for TCM Bushen Recipe.Syndrome and vitamin D deficiency have similar pathological changes,so it is suggested that Danggui Buxue Decoction may regulate osteoporosis by regulating the vitamin d axis.

Effect of Danggui Buxue Decoction on the expression of VDR,CYP27B1,CYP19,and ERβin the ovary of osteoporosis rats

Investigate the effects of the classic ancient prescription Danggui Buxue decoction on the vitamin D receptor,25-hydroxyvitamin D-1αhydroxylase,estrogen synthesis aromatase and estrogen receptorβmRNA and protein expression in osteoporotic rats.The classic ancient prescription Danggui Buxue decoction may affect the levels of estrogen synthesis aromatase,estrogen receptorβ,FSH,and Klotho in the body through regulating the expression of ovarian vitamin D receptor and 25-hydroxyvitamin D-1αhydroxylase to achieve the therapeutic effect of retinoic acid-induced osteoporosis in rats.The results of this experiment showed that compared with the control group,the serum FSH level of the model group was significantly increased,the Klotho level was decreased,the relative expression of ovarian tissue CYP27B1,CYP19,ERβmRNA and protein was significantly reduced,and the relative expression of vitamin D receptor mRNA and protein was significantly rise.After the intervention of the classic ancient prescription Danggui Buxue decoction and vitamin D,compared with the model group,the serum FSH content decreased,Klotho content increased,ovarian CYP27B1,CYP19,ERβmRNA and protein expression significantly increased,ovarian vitamin D receptor mRNA and protein expression significantly decreased.Based on the effect of the classic ancient prescription Danggui Buxue decoction on the vitamin D system,combined with the results of this experiment,it is concluded that the classic ancient prescription Danggui Buxue decoction may affect the levels of CYP19,ERβ,follicle-stimulating hormone,and Klotho in the body by regulating the expression of ovarian VDR and CYP27B1.The specific mechanism of the treatment of ovarian injury in osteoporosis rats needs further study.Background:Investigate the effects of the classic ancient prescription Danggui Buxue decoction on the vitamin D receptor,25-hydroxyvitamin D-1αhydroxylase,estrogen synthesis aromatase and estrogen receptorβmRNA and protein expression in osteoporotic rats.Methods:The experiment was divided into 6 groups:control group,model group(retinoic acid 100 mg/kg/d),vitamin D group(calcitriol 30 ng/kg/d),the classic ancient prescription Danggui Buxue decoction high,middle and low dose group(7.2 g/kg/d,3.6 g/kg/d,1.8 g/kg/d).Enzyme-linked immunosorbent assay method was used to detect the effects of different doses of the classic ancient prescription Danggui Buxue decoction on serum follicle-stimulating hormone and Klotho levels in retinoic acid-induced osteoporosis rats;real-time fluorescence quantitative PCR was used to detect the classic ancient prescription Danggui Buxue decoction on retinoic acid effect of ovary vitamin D receptor,25-hydroxyvitamin D-1αhydroxylase,estrogen synthesis aromatase,estrogen receptorβmRNA expression in induced osteoporosis rats;Western-blot detection of the classic ancient prescription Danggui Buxue decoction on retinoic acid-induced osteoporosis ovary vitamin D receptor,CYP27B,estrogen synthesis aromatase,estrogen receptorβprotein The impact of expression.Results:Compared with the control group,the serum follicle-stimulating hormone level of the model group was significantly increased,the Klotho level was decreased,the relative expression levels of 25-hydroxyvitamin D-1αhydroxylase,estrogen synthesis aromatase,estrogen receptorβmRNA and protein in the ovarian tissue were significantly decreased,and the relative expression levels of vitamin D receptor mRNA and protein were significantly increased.After the intervention of the classic ancient prescription Danggui Buxue decoction and vitamin D,compared with the model group,the serum follicle-stimulating hormone content decreased,Klotho content increased,ovarian 25-hydroxyvitamin D-1αhydroxylase,estrogen synthesis aromatase,estrogen receptorβmRNA and protein expression significantly increased,ovarian vitamin D receptor mRNA and protein expression significantly decreased.Conclusion:The classic ancient prescription Danggui Buxue decoction may affect the levels of estrogen synthesis aromatase,estrogen receptorβ,follicle-stimulating hormone,and Klotho in the body through regulating the expression of ovarian vitamin D receptor and 25-hydroxyvitamin D-1αhydroxylase to achieve the therapeutic effect of retinoic acid-induced osteoporosis in rats.

Comprehensive analysis of the potential biological mechanism of Danggui Buxue Decoction in the treatment of Thalassemia

Background:This study aimed to deeply explore the active components of Danggui Buxue Decoction(DBD)through systematic network pharmacology and molecular docking methods and to demonstrate its mechanism of regulating Thalassemia.Methods:Obtain and screen the active ingredients and targets of DBD from the TCMSP database.Use the GeneCards database to search for the gene corresponding to the target.The target protein-protein interaction(PPI)network was built using STRING database.A DBD-drug-Tha-target PPI network was established,and its core target network was analyzed using Cytoscape software.Then,enrichment analysis of DBD core targets was performed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and their binding activities were verified by molecular docking.Results:Finally,19 active ingredients and 504 targets were obtained from DBD,of which 98 targets were repeated with the related targets of Tha.The major genes include HSP90AA1,IL-6 and HRAS.Through the final analysis,we found that the main mechanisms of DBD in the treatment of thalassemia include increasing the expression of the γ-globin gene in red blood cells,inducing fetal hemoglobin and reducing the inflammatory response.Conclusion:The potential mechanism of DBD improving thalassemia can be preliminarily predicted by network pharmacology and molecular docking,which can provide some reference for clinical treatment.

The Latest Research Advances of Danggui Buxue Tang as an Effective Prescription for Various Diseases: A Comprehensive Review

Danggui Buxue Tang(DBT)is composed of Astragali Radix and Angelicae Sinensis Radix in a weight ratio of 5:1.The recipe of the decoction is simple,and DBT has been widely used in the treatment of blood deficiency syndrome for more than 800 years in China.Studies on its chemical constituents show that saponins,flavonoids,volatile oils,organic acids,and polysaccharides are the main components of DBT.Many techniques such as third-generation sequencing,PCR-denaturing gradient gel electrophoresis,and HPLC-MS have been used for the quality control of DBT.DBT has a wide range of biological activities,including blood enhancement,antagonizing diabetic nephropathy,cardiovascular protection,immunity stimulation,estrogen-like effect,and antifibrosis,among others.In this paper,we summarize the recent research advances of DBT in terms of its components,pharmacological activities,and possible mechanisms of action as well as provide suggestions for further research.

Protective Effects of Danggui Buxue Tang on a Human Umbilical Vein Endothelialcell Damage Induced by Advanced Glycation End Products

Advanced glycation end products (AGEs) have been regarded as a pivotal inducer in diabetes and kinds of diabetic nephropathy. The present studies explored the effects of Danggui Buxue Tang (DBT) that is a Chinese medicinal de- coction on negative charge to Human Umbilical Vein Endothelial Cell (HUVEC) and the related mechanism. Alcian blue staining was established to evaluate the intensity of negative charge on HUVEC. Proteoglycan expressions of AGP and avidin were determined by SDS-PAGE. We observed that DBT can significantly increase negative charge on HU-VEC and up-regulated AGP and avidin expressions and ameliorate AGEs-induced HUVEC apoptosis. Therefore, all results showed DBT had prevention effects against the progression of AGEs-induced damage, and this decoction might be promising agent against proteinuria in diabetic nephropathy.

Mechanism of Danggui Sini Decoction(当归四逆汤)for Atherosclerosis Obliterans Based on Network Pharmacology and Molecular Docking

Objective:Based on network pharmacology and molecular docking,we want to explore the pharmacological effects and mechanism of Danggui Sini Decoction in the treatment of lower extremity arteriosclerosis obliterans.Methods:Using TCMSP database to search the main active components of Danggui Sini Decoction(当归四逆汤,DSD)and their related targets,Cytoscape3.8.1 software was used to construct a"component-disease-target"interaction network.Meanwhile,DAVID database was used to enrich the key target genes with GO and KEGG functions.And we used Auto Dock Tools 1.5.6 for molecular docking.Results:A total of 45 candidate active molecules and 250 potential target proteins related to ASO were screened.Key genes such as TNF,IL6,VEGFA,MMP9,IL1B,CCL2,CXCL8,ICAM1,VCAM1,and IL10 are mainly through TNF signaling pathway,HIF-1 signaling pathway,cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway and other biological pathways exert their effects.The results of molecular docking showed that 5UUI-sesamin,5UUI-paeoniflorin,4XCT-sesamin,and 4XCT-sesamin have extremely strong binding ability.Conclusion:Danggui Sini Decoction(当归四逆汤,DSD)can synergistically exert pharmacological effects through multiple components,multiple targets,and multiple pathways.On the basis of regulating immunity and inhibiting smooth muscle proliferation,it can prevent the occurrence and development of ASO.

Danggui Sini decoction treatment of refractory allergic cutaneous vasculitis:A case report

BACKGROUND Allergic cutaneous vasculitis(ACV)is a difficult disease to treat.At present,there is no effective treatment for this condition.Traditionally,immunosuppressants and hormones have been primarily used in its management,but the treatment effect is suboptimal,and it has several side effects.CASE SUMMARY We present the case of a 19-year-old woman who presented at our hospital with a four-year history of symmetric skin lesions mainly affecting her lower extremities.She had previously undergone treatment with prednisolone acetate,cetirizine hydrochloride,and loratadine tablets but had not experienced any relief in her condition.Thereafter,she was treated with oral traditional Chinese medicine.Her skin damage gradually improved within two months of treatment initiation.After six months,the skin ulcers had completely subsided.No evidence of skin ulcer recurrence was observed during the subsequent follow-up.This report presents the first case of a female patient who received oral Danggui Sini decoction for the treatment of ACV.CONCLUSION Danggui Sini decoction may be a promising oral treatment for ACV patients.

Danggui Niantong decoction ameliorates joint inflammation and cardiopulmonary injury in TNF-Tg mice

Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.

Protection of Ultra-filtration Extract from Danggui Buxue Decoction(当归补血汤) on Oxidative Damage in Cardiomyocytes of Neonatal Rats and Its Mechanism

Objective： To investigate whether the administration of the ultra-filtration extract from Danggui Buxue Decoction （当归补血汤, EDBD） was able to protect cardiomyocytes from oxidative injury of rats induced by hydrogen peroxide （H2O2） and its potential mechanism. Methods： Myocardial cells from 1- to 2-day-old neonatal rats were cultured in Dulbecco＇s modified Eagle＇s medium low-glucose and Ham＇s F12 medium （1：1）, and the cellular injury was induced by H2O2. The ultra-filtration extract mixture from Angelica sinensis and Hedysarurn po/ybotrys was given in three doses of 3.75, 7.5, and 15 mg/mL. Morphological changes of cardiomyocytes were observed by microscope. Survival rate of myocardial cells was assessed using 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （Ml-r） assay. The cardiomyocyte damages were estimated by detecting lactate dehydrogenase （LDH） and creatine kinase （CK） releases in the medium, superoxide dismutase （SOD） activities, and intracellular malondialdehyde （MDA） and myeloperoxidase （MPO） contents. The levels of caspase-3 and heat shock protein 70 （hsp70） mRNA expression in cardiomyocytes were measured by reverse transcription polymerase chain reaction. Results： The EDBD could protect the cardiomyocytes from H202 injury in a dose- dependent manner （3.75, 7.50, and 15.00 mg/mL）. The EDBD could significantly decrease LDH and CK leakages and intracellular MDA and MPO contents, increase SOD activity, up-regulate hsp70 expression, and down-regulate caspase-3 expression. Conclusion： The EDBD has protection on cardiomyocytes injured by H202 through improving cell antioxidant ability, up-regulating hsp70 expression, and inhibiting caspase-3 activity.

Effects of Danggui Buxue Decoction (当归补血汤) on Lipid Peroxidation and MMP-2/9 Activities of Fibrotic Liver in Rats

Objective:To explore the mechanism of Danggui Buxue Decoction(当归补血汤,DBD) on the liver fibrosis related to hepatic lipid peroxidation and matrix metalloproteinases(MMP) -2/9 activities.Methods: The liver fibrosis in 28 rats was induced by an injection of carbon tetrachloride(CCl_4) and fed with high lipid and low protein diet for 6 weeks,the model rats were randomly divided into the model group and DBD treated group,14 in each group,and another 10 rats as the normal group were observed as well.Rats in the DB...

Danggui Buxue decoction ameliorates lipid metabolic defects involved in the initiation of diabetic atherosclerosis;identification of active compounds

OBJECTIVE: To determine the constituent compounds of Danggui buxue decoction(DBD) involved and the potential mechanisms mediating its effects, with specific reference to lipids playing a role in the initiation of diabetic atherosclerosis.METHODS: Liquid chromatography-tandem mass spectrometry was used to identify and quantify the absorbed bioactive compounds(ABCs) present in DBD. Goto-Kakizaki(GK) rats were randomly allocated to a diabetes atherosclerosis(DA) group, a DBD group, and an ABC group(10 per group), which were all high-fat diet-fed. The treated rats were administered DBD(4 g/kg) or ABCs(in amounts equal to those present in DBD) once daily for 28 d, and a control group of Wistar rats were administered vehicle. Body mass gain, fasting blood glucose, and homeostasis assessment of insulin resistance(HOMAIR) were measured. Serum triglyceride(TG), cholesterol(CHOL), high density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDLC) and tumor necrosis factor-α(TNF-α) concentrations were determined. Hematoxylin and eosin staining and microscopy were used to characterize the abdominal aorta and the expression of lipogenic genes was quantified in this vessel.RESULTS: Seven ABCs were identified in rat serum:ferulic acid, formononetin, calycosin, astragaloside,caffeic acid, ligustilide, and butyphthalide. DBD significantly reduced HOMA-IR, the serum concentrations of TG, CHOL, and LDL-C, and the expression of the lipogenic genes monocyte chemotactic protein1, Fas, intercellular adhesion molecule 1, and Cd36 in aorta;and significantly increased the mRNA expression of Scd1 in aorta.CONCLUSION: DBD affects lipid metabolism in the early stage of atherosclerosis in diabetic GK rats,with the mechanism likely involving the regulation of lipid metabolic genes in vessels. The contribution of ABCs to the effect of DBD on lipid metabolism was 24%-101%.

Efficacy of Auxiliary Therapy with Danggui Buxue Decoction No.1(当归补血汤1号) in Treating Patients of Non-small Cell Lung Cancer at Peri-operational Stage

Objective:To observe the therapeutic efficacy of Danggui Buxue Decoction No.1(当归补血汤1号,DB1) in treating patients of non-small cell lung cancer(NSCLC) at the peri-operational stage and its impact on the patients immune function.Methods:Eighty-two NSCLC patients were randomly assigned to two groups equally,the control group and the test group,they were given conventional treatment,while to the test group, DB1 were given additionally.The observation was conducted by testing the changes of T-lymphocyte subsets,...

Efficacy of Danggui Buxue decoction(当归补血汤)on diabetic nephropathy-induced renal fibrosis in rats and possible mechanism

OBJECTIVE:To observe the efficacy of Danggui Buxue decoction(当归补血汤,DBD) on diabetic nephropathyinduced renal fibrosis in rats,and to study the possible mechanism.METHODS:Sixty male Goto Kakizaki(GK) rats were randomly assigned to the model group,gliquidone group,astragaloside Ⅳ group,and high-,medium-and lowdoses DBD groups.After 8 weeks,changes in body weight,blood glucose,serum creatinine,serum urea nitrogen,and total cholesterol were observed.Changes in transforming growth factor-β1(TGF-β1),Smad3,and Smad5 pathways and the expression of the fibrosisrelated proteins collagen Ⅳ(col Ⅳ),α-smooth muscle actin(α-SMA),and vimentin were assessed.The degree of renal fibrosis was observed by immunohistochemistry and Mason staining.The expression of interleukin 6(IL-6),interleukin 10(IL-10),tumor necrosis factor(TNF-α),and C-reactive protein(CRP) in the kidneys was assessed using enzyme linked immunosorbent assay.RESULTS:Our experiments showed that DBD effectively reduced blood glucose,blood urea nitrogen,and creatinine levels after 8 weeks of administration,improved renal function in diabetic rats,alleviated renal fibrosis,and reduced the renal tissue levels of IL-6,IL-10,TNF-α,and CRP.Furthermore,DBD decreased the expression of TGF-β1,Smad3,col IV,α-SMA,and vimentin in renal tissues and increased the expression of Smad5.CONCLUSIONS:DBD ameliorates diabetic renal interstitial fibrosis by modulating the TGF-β1/Smads pathway.

Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction,Fe and rhEPO based on colon cancer-related anemia model and gut microbiota modulation

Colon cancer-related anemia(CCRA)is mainly caused by systemic inflammation,intestinal bleeding,iron deficiency and chemotherapy-induced myelosuppression in colon cancer.However,the best therapeutic schedule and related mechanism on CCRA were still uncertain.Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction(DBD),Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper.Here,CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p.oxaliplatin,rhEPO+DBD high dosage+Fe(EDF)and rhEPO+DBD high dosage(ED)groups had the best blood enrichment effect.Attractively,EDF group also showed antitumor activity.The sequencing results of gut microbiota showed that compared to P group,the relative abundances of Lachnospiraceae and opportunistic pathogen(Odoribacter)in ED and EDF groups were decreased.Interestingly,EDF also decreased the relative abundances of cancer-related bacteria(Helicobacter,Lactococcus,Alloprevotella)and imbalance-inducing bacteria(Escherichia-Shigella and Parabacteroides)and increased the relative abundances of butyrate-producing bacteria(Ruminococcaceae_UCG-014),however,ED showed the opposite effects to EDF,this might be the reason of the smaller tumor volume in EDF group.Our findings proposed the best treatment combination of DBD,rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.

基于化学成分与药理作用评价当归-黄芪药对配方颗粒汤剂与传统汤剂的差异

目的评价当归-黄芪药对配方颗粒汤剂(DGD)与传统汤剂在化学成分和药理效应方面的差异,为合理应用该配方颗粒提供参考。方法以原料来源批次统一和不统一2种对比方式,设不同样品组,采用高效液相色谱(HPLC)法建立特征图谱,从特征图谱相似度、成分种类、指标成分含量、共有峰面积等角度对化学成分进行评价;采用失血性血虚模型小鼠评价药效。结果①DGD特征图谱与传统汤剂相似度较高(相似度>0.87);②共有色谱峰数目不一致,传统汤剂-自购饮片和传统汤剂-A厂饮片共有色谱峰各12个,A厂DGD共有色谱峰15个,B厂DGD共有色谱峰10个;③A厂DGD中阿魏酸、毛蕊异黄酮苷含量高于传统汤剂(P<0.05);B厂DGD与传统汤剂阿魏酸含量差异无统计学意义,但毛蕊异黄酮苷含量较传统汤剂低(P<0.05);④DGD共有峰面积总和与传统汤剂相比,自购传统汤剂、A厂传统汤剂及A厂配方颗粒、B厂配方颗粒中各成分含量相对比值分别为1.00、0.96、2.14、0.60;⑤DGD及传统汤剂均能明显促进失血性贫血模型小鼠血红蛋白(Hb)、红细胞(RBC)恢复(P<0.01);与模型对照组比较,除B厂DGD组外均差异有统计学意义(P<0.05);A厂DGD与传统汤剂差异无统计学意义,B厂DGD与传统汤剂差异有统计学意义(P<0.01)。结论无论原料来源批次是否一致,DGD与传统汤剂在化学成分上均存在一定差异;在药理作用上,来源于同一批次饮片制备的DGD与传统汤剂对改善失血性贫血药效相当,来源于不同批次饮片制备的DGD与传统汤剂在药效上存在一定差异;不同来源批次的饮片和不同制备工艺造成不同厂家配方颗粒存在质量差异,说明国家统一配方颗粒质量标准及制定相关过程规范具有必要性与紧迫性。

当归多糖对再生障碍性贫血小鼠骨髓Th17/Treg细胞平衡及相关炎性因子蛋白表达的影响

目的探究当归多糖(Angelica polysaccharide,APS)对再生障碍性贫血(aplastic anemia,AA)小鼠骨髓Th17/Treg细胞平衡及相关炎性因子蛋白表达的影响。方法50只雄性BALB/c小鼠随机分为正常组、模型组、环孢素A组、APS低、高剂量组,利用射线照射联合异源淋巴细胞输注的方法制备再生障碍性贫血小鼠模型。建模后灌胃给药28 d,观察小鼠一般情况、体重变化、脾指数,检测外周血基本血液学参数变化,HE染色评价小鼠骨髓组织病理变化;ELSIA法检测骨髓TGF-β1、IL-10、IL-17A、IL-6等蛋白表达水平;FCM检测骨髓Th17、Treg细胞比例及Th17/Treg细胞平衡变化。结果与正常组相比,模型组小鼠活动笨拙,精神萎靡,眼睑唇色耳廓颜色苍白,进食饮水量减少;体重及脾指数均明显下降;外周血红细胞、白细胞、血小板计数及血红蛋白浓度均明显降低;骨髓组织结构紊乱,造血组织增生度明显减低;IL-17A、IL-6蛋白表达明显上调,TGF-β1、IL-10蛋白表达明显下调;骨髓Th17细胞比例明显增高,Treg细胞比例明显降低,Th17/Treg细胞比值显著升高(P<0.01)。与模型组相比,APS低、高剂量组一般状况均改善,进食量及饮水量增加,体重、脾指数明显升高,外周血红细胞、白细胞、血小板计数及血红蛋白浓度明显升高(P<0.05),骨髓组织结构改善,造血组织增生度升高(P<0.05);IL-17A、IL-6蛋白表达明显下调,TGF-β1、IL-10蛋白表达明显上调(P<0.05或P<0.01);骨髓Th17细胞比例明显降低,Treg细胞比例明显升高,Th17/Treg细胞比值显著下降(P<0.01)。结论当归多糖能改善AA小鼠骨髓造血功能,其机制可能是通过调节Th17/Treg细胞平衡来实现。