Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Clinical Effect of Modified Shengyang Yiwei Decoction in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome due to Spleen and Stomach Weakness

Objective:To explore the therapeutic effect of Shengyang Yiwei Decoction in patients with diarrhea-predominant irritable bowel syndrome(IBS)due to spleen and stomach weakness.Methods:40 patients with diarrhea-predominant IBS who were treated from April 2018 to April 2020 were taken as samples.TCM(traditional Chinese medicine)syndrome differentiation found that they were all due to spleen and stomach weakness.They were randomly divided into two groups.Group A was treated with modified prescriptions of Shengyang Yiwei Decoction,while Group B was treated with Western medicine.The therapeutic effects in the two groups were compared.Results:The treatment efficacy in Group A was higher than that in Group B(P<0.05);the symptom scores of Group A such as loose stools,chills,physical weakness,poor appetite,and abdominal distension after meals were all lower than those in Group B(P<0.05);the SF-36(36-Item Short Form Health Survey)scores of patients with diarrhea-predominant IBS in Group A were higher than those in Group B(P<0.05);the treatment satisfaction of Group A was higher than that of Group B(P<0.05).Conclusion:Treatment of diarrhea-predominant IBS patients with spleen and stomach weakness by Shengyang Yiwei Decoction can promote the disappearance of gastrointestinal discomfort symptoms,improve the quality of life,and enhance treatment efficacy.Hence,it is an efficient and feasible treatment for diarrhea-predominant IBS due to spleen and stomach weakness.

Clinical Observation of the Therapeutic Effects of Wenzhong Hewei Formula in Treating Spleen and Stomach Qi Deficiency Syndrome in Internal Medicine Diseases

Objective:To observe the clinical efficacy and safety of Wenzhong Hewei Formula in treating spleen and stomach qi deficiency syndrome in internal medicine diseases.Methods:Sixty patients with spleen and stomach qi deficiency syndrome admitted to the hospital from April 2022 to June 2023 were randomly divided into observation and control groups,with 30 patients in each group.The control group received conventional internal medicine treatment,while the observation group was additionally treated with Wenzhong Hewei Formula on the basis of conventional treatment.Both groups were treated for 4 weeks.Results:The total effective rate of treatment in the observation group was higher than that of the control group(P<0.05).After treatment,the traditional Chinese medicine syndrome scores of both groups were significantly lower than before treatment,with the observation group showing a more pronounced reduction(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Wenzhong Hewei Formula can effectively improve clinical symptoms in patients with spleen and stomach qi deficiency syndrome,enhance clinical efficacy,and have a high level of safety,making it worthy of clinical promotion.

Current concept of Spleen Stomach theory and Spleen deficiency syndrome in TCM

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Intervention effect of traditional Chinese medicine Yi Tang Kang on metabolic syndrome of spleen deficiency

Objective:To investigate effects of herbal compound Yi Tang Kang on the spleen deficiency metabolic syndrome.Methods:Forty male Wistar rats were randomly divided into two groups:the normal control group and the MS spleen deficiency syndrome group.The control group rats were fed with standard diet and water,while MS spleen deficiency syndrome group with high fat diet and low dose intraperitoneal injection of slreptozocin.which swam to the endurance limit.After 12 weeks,the MS spleen deficiency syndrome group was randomly divided into two groups,with 13 rats in each group.Flats in model group were fed with high fat diet and conlinuouly administered with daily saline,and rats in intervention group with high fat diet were trated with traditional Chinese medicines Yi Tang Kang by gavage,2 mL/200 g at the same lime every day.10 weeks later,the expression of serum proteomics was investigated through abdominal aortic puncture and separation of serum,using isotope labeling technique,high performance liquid chromatography and four bar-Orbitrap mass spectrometer.Results:After treatment with traditional Chinese medicine yitangkang,in the model group,important carboxylesterase and retinal guanylate cyclase 2 precursor were upregulated.As for intervention group,these indesxes were raised,but immunoglobulin IgG,carnitine acetyltransferase,tubulin beta-5,and Gan Lu sugar binding protein C were down-regulated.At the same time,some new biological active substances,such as protein tyrosine kinase,beta glucosidase were also found.Conclusions:Traditional Chinese medicines Yi Tang Kang could regulate glucose and lipid metabolism in rats with spleen deficiency syndrome.

Study on the Expression of Organic Anion Transporting Polypeptide (oatp2a1) in Rat with Spleen Deficiency Syndrome and the Exploration of Clinical Significance

Objective: to explore the mechanism of transportation and transformation of dampness by the way of the expression of organic anion transporting polypeptide (oatp) superfamily member 2a1 (oatp2a1) mRNA in rat with spleen deficiency syndrome and the significance in transportation and transformation of dampness. Methods: 32 wistar male rats were divided randomly into four groups: normal group (n = 6), normal + AA group (n = 6), spleen deficiency group (n = 10), Spleen deficiency + AA group (n = 10). After reserpine-induced spleen deficiency model was made, intragastric administration of aristolochic acid (AA) was adopted for three days, the expression of oatp2a1 mRNA were detected in the tissues of lung, liver, kidney, stomach, small intestine and large intestine in four groups by using Fluorescent Quantitative-Polymerase Chain Reaction (FQ-PCR). Results: the expression of oatp2a1 mRNA in above six tissues could be detected. The ex-pression of oatp2a1 mRNA in liver tissue of rat with spleen deficiency syndrome was up-regulated compared to normal group (P = 0.035, P < 0.05), the expression of oatp2a1 mRNA in small intestinal tissue of rat with spleen deficiency syndrome was down-regulated compared to normal group (P = 0.004, P < 0.01), the expression of oatp2a1 in intestinal tissue in normal + AA group is down-regulated compared to normal group (P = 0.032, P < 0.05). Conclusions: oatp2a1 might be one of the material basis involved in transportation and transformation of dampness. The changes of expression of oatp2a1 mRNA in small intestine, liver tissue suggests that small intestine, liver might play an important role in the transportation and transformation of dampness in the state of spleen deficiency. We further concluded that the function of spleen’s governing transportation and transformation of dampness was not only including the function of the gastrointestinal, but also part of the liver function in some degree, which needs to be further studied.

CLINICAL STUDY ON SPLEEN-STOMACH-REINFORCING MOXIBUSTION TREATMENT OF DIARRHEA-TYPE IRRITABLE BOWEL SYNDROME

In the present paper, the therapeutic effect of spleen- stomach- reinforcing moxibustion for treatment of irritable bowel syndrome (IBS) is observed and its underlying mechanisms on immunity are analyzed. A total of 72 IBS patients are randomly divided into moxibustion group (n= 46) and acupuncture group (control group, n = 26). Acu-points used are Zhongwan (CV 12), Qihai (CV 6) and Zusanli (ST 36), etc. Serum IgG, IgA and IgM contents, blood T-lympocytes (T3+, T4+, T8+) counts, T4+ /T8+, cancer embryonic antigen (CEA) content, serum IL-2 and slL-2R contents are assayed for evaluating changes of the immunocompetence. After two courses of treatment (24 sessions), results show that in moxibustion group, 25 cases (54.35%) are cured, 17 experience improvement in clinical symptoms and 4 have no apparent changes, with an effective rate of 91.30% ; in control group, 8 cases (30. 78%) are cured, 12 experience improvement and 6 have no marked improvement, with an effective rate of 76.92% . The therapeutic effect of moxibustion is significantly superior to that of acupuncture (P<0.01). In addition, moxibustion can effectively rectify abnormal immune function and stabilize human's immunity. This research provides a reliable experimental basis for clinical application of 'principal prescription of moxibustion for reinforcing the spleen and stomach'.

Unusual association of Axenfeld-Rieger syndrome and wandering spleen:A case report

BACKGROUND Axenfeld-Rieger syndrome(ARS)is an autosomal dominant genetic disease characterized by ocular developmental disorders and its association with torsion of wandering spleen(WS)has not been reported to date to the best of our knowledge.This study aimed to describe a rare case of ARS observed at our emergency department.CASE SUMMARY A 25-year-old female presented with a constant lower abdominal pain of increasing severity.Diagnostic computed tomography with intravenous contrast material showed a non-homogenously enhanced splenic parenchyma with a twisted vascular pedicle.Further,an emergent laparoscopic exploration was performed,and an ischemic spleen without its normal ligamentous attachments was noted.Notably,the spleen did not regain its normal vascularity after detorsion;thus,we performed the laparoscopic total splenectomy.The postoperative course was uneventful,and the patient was discharged on the 5th postoperative day.This case demonstrates a rare association of WS and ARS.CONCLUSION Early diagnosis of WS in the emergency department is important to prevent pedicle torsion or splenic necrosis and to avoid splenectomy.

The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin

Objective To analyze the basic characteristics,drug features,prescription rules,and drug-symptom relationships of patients in the splenic deficiency and impairment stage,by data mining of medical records under the New Theory on Spleen Dampness Syndrome(Pi Dan Xin Lun,《脾瘅新论》).Methods Medical records listed in the“New Theory on Spleen Dampness Syndrome-Under-standing and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”,and which were diagnosed with the spleen dampness syndrome at the splenic de-ficiency and impairment stage,during January 2004 and December 2016 were selected.These patients’data,including basic information,clinical symptoms,laboratory examination res-ults,traditional Chinese medicine(TCM)and western medicine diagnoses,treatment meth-ods,prescriptions,etc.,were collected.The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software,followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug,drug-symptom,and drug-western medicine indices.Results(i)A total of 51 medical records were included,involving 17 types of syndromes.Among them,the top three with frequency≥3 included“Phlegm and blood stasis,and thoracic obstruction”“Deficiency-weakness of the spleen Qi,and static blood blocking collat-erals”,and“Deficiency-weakness of the spleen Qi,and static blood blocking collaterals”.Al-ternatively,of the 14 treatment methods,the top three treatments with frequency of≥3 in-cluded“Activating Yang and eliminating turbidity,and removing phlegm and dredging chan-nel blockage”“Strengthening the spleen and benefiting Qi,and eliminating phlegm to activ-ate the channels”,and“Warming Yang and benefiting Qi,and expelling cold to remove ob-structions”.Among the 15 prescriptions,the top three used with frequency≥3 included Huangqi Guizhi Wuwu Tang(黄芪桂枝五物汤),Gualou Xiebai Banxia Tang(瓜蒌薤白半夏汤),and Ganjiang Huangqin Huanglian Renshen Tang(干姜黄芩黄连人参汤).Lastly,of the 83 drugs used for a total of 476 times,those with frequency≥15 included Huanglian(Coptid-is Rhizoma),Huangqi(Astragali Radix),Jiudahuang(Wine-processed Rhei Radix et Rhizoma),Jixueteng(Spatholobi Caulis),Shengjiang(Zingiberis Rhizoma Recens),Huangqin(Scutellariae Radix),and Guizhi(Cinnamomi Ramulus).(ii)For the drug-drug associations,under the criteria of support≥15%and confidence=100%,seven second-order association rules,seven third-order rules,and six fourth-order roles were identified.The top-ranking rule of each was“Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”“Ganjiang(Zingiberis Rhizoma)+Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”,and“Baishao(Paeoniae Radix Alba)+Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatho-lobi Caulis)→Huangqin(Scutellariae Radix)”,respectively.Alternatively,the drug-symptom associations were analyzed under the criteria of support≥5%and confidence=100%,which derived eight second-order association rules,31 third-order rules,and 30 fourth-order rules.The top-ranking association rule of each order was“Huangqi(Astragali Radix)→Limb ed-ema”“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)→Limb numbness and pain”,and“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)+Huangqi(As-tragali Radix)→Limb numbness and pain”,respectively.Similarly,the drug-western medi-cine index associations were investigated under the criteria of support≥5%and confidence=100%,and five second-order association rules,16 third-order rules,and 16 fourth-order rules were identified.In this category,the top-ranking association rule of each order was“Qinpi(Fraxini Cortex)→Uric acid”“Huanglian(Coptidis Rhizoma)+Ganjiang(Zingiberis Rhizoma)→Glycated hemoglobin”,and“Huanglian(Coptidis Rhizoma)+Ganjiang(Zing-iberis Rhizoma)+Huangqin(Scutellariae Radix)→Glycated hemoglobin”,respectively.Conclusion Through association rule mining,this study objectively and quantitatively demonstrated the drug-drug,drug-symptom,and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin.The results indicated that treatment for these patients adopted the“state-target”syndrome differentiation method.The drug combination was characterized by“small prescriptions”,targeting both the patient’s symptoms and signs(syndrome target)and western medicine indices(treatment target).This study could provide references for future research on the academic thoughts and medical experience of Academi-cian TONG Xiaolin.

Biological basis of “depression with liver-qi stagnation and spleen deficiency syndrome”: A digital gene expression profiling study

Objective:To investigate the biological basis of“depression with liver-qi stagnation and spleen deficiency syndrome”.Methods:A digital gene expression profiling method was conducted to explore global changes in the mRNA transcriptome in a rat model of depression with liver-qi stagnation and spleen deficiency syndrome.Real-time quantitative polymerase chain reaction(q-PCR)was performed to verify the five genes most interest based on the Kyoto Encyclopedia of Genes and Genome(KEGG)analysis.Sini San,which disperses stagnated liver qi and strengthens the spleen,was administered to the model rats to observe whether it could reverse these genetic changes in the liver.Results:Forty-six differentially expressed genes were identified.Three of the five genes of most interestdHnf4a,Hnf4g and Cyp1a1dbased on KEGG analysis,were confirmed by realtime q-PCR.Sini San reduced the gene expression changes of Hnf4a,Hnf4g and Cyp1a1 in the rat model.Conclusions:Hnf4a,Hnf4g and Cyp1a1 are involved in“depression with liver-qi stagnation and spleen deficiency syndrome”.These findings indicate that depressed rats with liver-qi stagnation and spleen deficiency syndrome are at risk of liver diseases.Furthermore,our results will inform exploration of the etiology of depression and help in the development of effective therapeutic strategies.

Rules of Ren Shunping's prescription for trearing Spleen Deficiency and Qi Stagnation Syndrome of Functional Dyspepsia Based on Data Mining

Objective:To explore the medication rules of Professor Ren Shunping treating spleen deficiency and qi stagnation syndrome of functional dyspepsia,so as to provide reference for clinical prevention and development of new drugs.Methods:The 144 Chinese herbal formulas considered as active prescribed by professor Ren Shunping for the first time treating the patients with spleen deficiency and qi stagnation syndrome of functional dyspepsia were collected,entered into TCM inheritance auxiliary platform(V2.5),and then mined by some data mining methods of the software,such as the association rules and unsupervised entropy hierarchical clustering.Results:This study involved 144 Chinese herbal formulas,including a total of 56 Chinese herbal medicines.Of these Chinese herbal medicines,the herbs of cold and warm nature,and pungent,bitter and sweet in flavors were used in a quite high frequency,all of which act on spleen,stomach,lungs,large intestine,liver and gallbladder meridians.One core Chinese herbal formula was excavated,composed of patchouli,perilla stem,radix bupleuri,scutellaria,ginger pinellia,codonopsispilosula,magnolia bark,tangerine peel,large-headed atractylodes,immature bitter orange,wood incense,fructus amomi,inula britannica chinensis,ginger,medicated leaven,fried rice and fried malt based on the association rules.And a total of 17 groups of core used drugs and 2 groups of new Chinese herbal formulas undiscovered were mined based on unsupervised entropy hierarchical clustering.Conclusion:In treating spleen deficiency and qi stagnation syndrome of functional dyspepsia,professor Ren is good at treating spleen deficiency and qi stagnation syndrome of functional dyspepsia from the perspective of"tong jiang",using the"five-in-one"strategy of strengthening the spleen,evacuating the liver,coming down qi from the stomach,dispersing lung,and bowel-reflexing to treat patients as a whole.And the herbal medicines were light in dose,lovely and mild in nature for the formulars.At the same time,he paid attention to the combination of syndromes and symptoms,and flexible arbitration.

The new idea of children with tic syndrome:regulating the five Zang-organs with spleen and stomach system as the center

The pediatric body of pure yang,the liver is often more than enough,the spleen is often insufficient,Yang moving surplus,and Yin essence is insufficient,at the same time,children are the body of immature yin and yang,prone to imbalance of yin and Yang,so deficiency of phlegm accumulation and endogenous liver wind,feel ill at ease,dysfunction of lung qi,Insufficiency of kidney yin are the fundamental pathogenesis of children with tic syndrome.This article discusses the relationship between children with tic syndrome and the five Zang-organs,and how to regulate the viscera through regulating the spleen and stomach system,treating both manifestation and root cause of disease,and put forward a new treatment that the spleen and stomach system should be taken as the center to regulate the five Zang-organs in children with tic syndrome,which should be resolved in order of importance and urgency and treated in stages.

Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B(CHB)Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome

Objective:This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common traditional Chinese medicine(TCM)Syndromes—damp heat syndrome and liver depression and spleen deficiency syndrome.Methods:According to the diagnostic criteria of Western medicine,TCM and screening exclusion criteria,65 cases of CHB with damp heat syndrome and 28 cases of CHB with liver depression and spleen deficiency syndrome were finally included in the study.All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing.16S rDNA of gut microbiota was sequenced using Illumina hiseq 2,500 high-throughput sequencing platform.Based on the optimized sequence,Operational Taxonomic Units(OTU)clustering analysis and taxonomic annotation were carried out.Results:The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients.Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales,Alphaproteobacteria and Lachnospira were higher in the damp heat syndrome.LDA Effect Size(LEfSe)analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusion:The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.

Theoretical Discussion on Treatment of Cubital Tunnel Syndrome Based on Theory of Liver,Spleen and Kidney

Cubital tunnel syndrome is a disease in which ulnar nerve is compressed by its surrounding tissues,and its main clinical manifestations are pain,sensory disturbance and dyskinesia.Its incidence rate is the second highest among peripheral nerve entrapment diseases,and it is one of the common clinical diseases.The theory of liver,spleen and kidney can guide the treatment of cubital tunnel syndrome with traditional Chinese medicine and acupuncture.By discussing the traditional Chinese medicine(TCM)pathogenesis and treatment principles of cubital tunnel syndrome,it provides modern medical theoretical support for TCM treatment of cubital tunnel syndrome.

Clinical study on fire needle acupuncture treating irregular menstruation with spleen deficiency syndrome

Objective:To observe the clinical efficacy of fire needle acupuncture in treating irregular menstruation with spleen deficiency syndrome.Methods:60 patients with spleen deficiency-irregular menstruation were randomly divided into treatment group and control group of 30 each.In the treatment group,fire needle acupuncture was used to insert into Guanyuan,Qihai,Pishu,Sanyinjiao,Zusanli and Taibai points,while the filiform needle was used to needle the corresponding acupoints in the control group.After 8 weeks of treatment,menstrual cycle,menstrual period,menstrual volume,irregular menstrual symptom score and spleen deficiency symptom score were recorded.Results:Both treatments could effectively improve the menstrual cycle,menstrual period and menstrual volume,but there was no statistical significance between the two groups(P>0.05).Both treatments were effective in regulating the symptoms of menstruation,and fire needle acupuncture was better than filiform needle(P<0.05).Both treatments relieved the symptoms of spleen deficiency,and fire needle acupuncture was better than filiform needle(P<0.05).In terms of overall curative effect,the curative effect of fire needle acupuncture therapy was significantly better than filiform needle therapy,and the difference was statistically significant(P<0.05).Conclusion:Fire needle acupuncture therapy could effectively regulate menstrual volume of patients with irregular menstruation of spleen deficiency syndrome,and relieve the symptoms of traditional Chinese medicine.

Efficacy of Pidan Jianqing decoction in treatment of type 2 diabetes with spleen deficiency and damp-heat syndrome

Introduction:This study aimed to assess the clinical efficacy of Pidan Jianqing decoction in the treatment of type 2 diabetes.Methods:A total of 72 patients with type 2 diabetes differentiated as spleen deficiency with damp-heat syndrome were randomly assigned to a treatment group(n=35)or control group(n=32).Patients in the control group received diet and exercise guidance and medication in the form of 0.5 g metformin hydrochloride tablets,while patients in the treatment group received Pidan Jianqing decoction in addition to the treatment given to the control group.Efficacy was evaluated after 8 weeks of treatment.Results:Efficacy was 91.4%in the treatment group versus 68.8%in the control group,which was a statistically significant difference(P<0.05).Significant group differences were also noted in the number of patients with improvement in symptoms such as dry mouth and polydipsia,frequency of urination and polyuria,abdominal distention and loss of appetite,fatigue and weakness,and sticky stools(all P<0.05),with greater improvement in the treatment group compared to the control group.The fasting blood glucose(FBG)and 2 h postprandial blood glucose levels significantly improved in both groups after treatment(P<0.05);however,there was no significant difference in glycated hemoglobin levels before and after treatment in both groups.Conclusion:Pidan Jianqing decoction can lower blood glucose levels and improve symptoms in patients with type 2 diabetes.

Pharmacokinetics of traditional Chinese syndrome and recipe:a hypothesis and its verification(Ⅰ)

AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and healthyanimals.The classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the presentstudy.The hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify R-PK.RESULTS The apparent first-order absorption[Ka,（13.61±2.56）h-1,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h-1mL-1],maximum drug concentration[Cmax,（4.82±1.23）μg·mL-1]of serum TMP inRMSDS were increased markedly（P【0.05）compared with those[Ka=（5.41±1.91）h-1,AUC=（5.20±2.57）μg·h-1·mL-1,Cmax=（2.33±1.77）μg·mL-1]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h-1,β=（0.06±0.03）h-1,the apparent first-orderintercompartmental transfer rate constants[K10=（0.24±0.07）h-1,K12=（0.11±0.02）h-1,K21=（0.11±0.02）h-1]of serum TMP in RMSDS weredecreased significantly（P【0.01）comparedwith those[K10=（0.88±0.20）h-1,K12=（1.45±0.47）h-1,K21=（0.72±0.22）h-1]of HR.However,no apparent differences occurredbetween HR and RMSDS treated with SJZD.Theserum FA concentration and its AUC[（5.6690±2.3541）μg·h-1·mL-1] in RMBSS were also higherthan those[AUC=（2.7566±0.8232）μg·h-1·mL-1]of healthy rabbits（P【0.05）.The Ka（11.51±2.82）h-1,AUC（0.84±0.17）μg·h-1·mL-1of LW & SM-derived TMP in serum weremuch lower（P【0.05）than those[Ka=（19.58±4.14）h-1,AUC=（1.27±0.26）μg·h-1·mL-1]ofLW-derived TMP in serum after oral decoctions.CONCLUSION The SDS and blood stasissyndrome state could affect significantly thepharmacokinetic parameters of drugs and theabnormal SDS pharmacokinetic parameters couldbe normalized by SJZD.The combination ofChinese medicine in TCR could reciprocallyaffect the pharmacokinetic parameters of othercomponents absorbed into the systemiccirculation.These results support the S-and R-PK hypothesis.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

Effect of Tong Xie Yao Fang on endogenous metabolites in urine of irritable bowel syndrome model rats

BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.

Exosomes promote the invasion and metastasis of hepatocellular carcinoma cells via an integrin-dependent manner in the spleen-deficient state

Background:To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency(SD)syndrome on hepatocellular carcinoma(HCC).Methods:In the present study,our model was established based on an HCC mouse model induced by diethylnitrosamine using reserpine to induce SD.Exosomes were isolated and purified from mouse plasma samples using an exosome isolation kit.Subsequently,we verified the pro-metastatic effects of exosomes from the HCC mice with SD on HCC cells by transwell assays,wound healing assays,phalloidin staining in vitro,and lung metastasis assay of mice in vivo.Finally,we further explored the detailed mechanism underlying the pro-metastatic effect of exosomes from the HCC mice with SD on HCC cells.Results:We found that SD promoted the malignant progression of HCC in mice.Exosomes from HCC mice with SD enhanced the invasion and metastasis of HCC cells in vitro and in vivo.Mechanistically,upregulation of integrinα1,integrinβ1,and integrinβ5 seemed to play a key role in mediating the pro-metastatic effect of exosomes isolated from the HCC mice with SD,which was largely abrogated upon co-treatment with a broad-spectrum integrin inhibitor.Conclusion:Our findings demonstrated that exosomes promote the invasion and metastasis of HCC cells via an integrin-dependent manner in the spleen-deficient state that would contribute to our better understanding of the role of SD in HCC progression in traditional Chinese medicine,and thus management of the disease.