Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation

Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Effects of Jiawei Wendan decoction on hippocampal p-CREB protein expression in a rat model of depression

BACKGROUND： Jiawei W＇endan decoction can elevate hippocampal brain-derived neurotrophic factor （BDNF） protein expression in rats with depression. It has been hypothesized that Jiawei Wendan decoction can exhibit antidepressant effects through the hippocampal signal transduction pathway of cyclic adenosine monophosphate response element binding protein （CREB）-BDNF. OBJECTIVE： Using phosphorylated-CREB （p-CREB） as an entry point, the present study was designed to observe intervention effects ofJiawei Wendan decoction compared with fluoxetine. DESIGN, TIME AND SETTING： A randomized, controlled, cellular biology experiment was performed at the Central Laboratory of Guangxi University of Traditional Chinese Medicine, MATERIALS： A total of 40 healthy, male, Sprague-Dawley rats were included in the present study. Rhizoma Acori Talarinowii （Shichangpu）, Flos Albiziae （Hehuanhua）, Rhizoma Pinelliae （Banxia）, Caulis Bambusae in Taeniam （Zhuru）, Fructus Aurantii Immaturus （Zhishi）, Poria （Fuling）, and Radix Bupleuri （Chaihu）, the primary ingredients ofJiawei Wendan decoction, were purchased from First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine. The raw drug was decocted at a concentration of 1.5 g/mL. Fluoxetine capsules were purchased from Shanghai Zhongxi Pharmaceutical Co., Ltd., China. METHODS： Following behavioral testing, 36 rats were selected from the initial 40 rats according to similar behavioral scores, and were randomly divided into 4 groups： model （n = 8）, Jiawei Wendan decoction-treated （n = I 0）, fluoxetine-treated （~ = 10）, and normal control （n = 8）. All rats, except for those in the normal control group, were separately raised in a chronic and unpredictable, mild-stimulation environment for 2 l days to establish a depression model. The Jiawei Wendan decoction-treated and fluoxetine-treated groups were intragastrically administered Jiawei Wendan decoction （12 g/kg/d） and fluoxetine （1.8 mg/kg/d）, respectively. The model and normal control groups received double-distilled water （2 mL/kg/d） once a day for a total of 21 days. MAIN OUTCOME MEASURES： Prior to depression induction and subsequent to administration, memory and degree of depression were measured by open field and tail suspension tests, respectively. At 24 hours after administration, p-CREB expression in the hippocampat CA3 region was analyzed by the immunohistochemical SABC method. RESULTS： Two rats from the Jiawei Wendan decoction-treated group, and one from the fluoxetine-treated group, died of unknown causes. The remaining rats in each group, except for one rat that was randomly selected from the fluoxetine-treated group, were included in the final analysis. Following administration, the model group exhibited significantly decreased numbers of hippocampal p-CREB-positive cells, horizontal and vertical movements, and significantly prolonged duration of immobility in tail-suspension test, compared with the normal control group （P 〈 0.01）. The numbers of p-CREB-positive cells, as well as horizontal and vertical movements, were significantly greater, and the duration of immobility was significantly shorter, in the Jiawei Wendan decoction and fluoxetine groups, compared with the model group （P 〈 0.05-0.01）. There was no significant difference in the above-mentioned three indices between the Jiawei Wendan decoction and fluoxetine groups （P 〉 0.05）. CONCLUSION： Jiawei Wendan decoction increased hippocampal p-CREB expression by influencing the rat hippocampal signal transduction pathway of CREB-BDNF. Jiawei Wendan decoction exhibited antidepressant effects equivalent to fluoxetine.

Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study

Hypertriglyceridemia is the third leading cause of acute pancreatitis(AP),and its incidence is increasing.Due to its relatively insidious etiology,it is easy to be ignored in the early stages.In China,Chaiqin Chengqi Decoction(CQCQD)has long been employed for treating AP.AIM To evaluate the effectiveness of CQCQD in patients diagnosed with mild/moderately severe hypertriglyceridemic AP(HTG-AP).METHODS In this study,the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected.The changes of blood lipids,gastrointestinal symptoms,and abdominal pain before and after treatment were analyzed and compared between the two groups.RESULTS Twenty patients were treated with the conventional HTG-AP regimen,and 19 patients were additionally treated with CQCQD.After receiving treatment,the triglycerides(TG)level of the CQCQD group was lower than that of the CQCQD group(3.14±0.25 mmol/L vs 4.96±0.47 mmol/L,P<0.01).After 3 d of treatment,the patients in the CQCQD group had more bowel movements than the control group(2.51±0.25 times vs 1.00±0.17 times,P=0.01).The gastrointestinal function of most patients returned to normal,and the acute gastrointestinal injury score was significantly lower than that of the control group(0.11±0.07 vs 0.42±0.11,P<0.01).CONCLUSION In patients with HTG-AP,CQCQD can significantly reduce the TG level,shorten the recovery time of defecation,significantly improve the gastrointestinal function.

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

An experimental model of schizophrenia was established using dizocilpine （MK-801）. Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance

Objective To evaluate the efficacy and safety of Huanglian Wendan Decoction(黄连温胆汤,HLWDD)alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.Methods The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1,2012 to April 1,2022 were searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Database,China BioMedical Literature Database(CBM),PubMed,Web of Science,Embase,and Cochrane Library databases.After being screening,the included literature was analyzed to evaluate the effective rate,Pittsburgh Sleep Quality Index(PSQI)score,traditional Chinese medicine(TCM)syndrome score,and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance.The subgroup analyzed the effect of HLWDD after different treatment courses,and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.Results Twenty-seven randomized controlled trials were finally included,with a total of 2395 patients.The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group[RR=1.14,95%CI(1.06,1.22),P=0.000].The PSQI score[SMD=-0.31,95%CI(-0.42,-0.20),P=0.000],TCM syndrome score[SMD=-0.40,95%CI(-0.67,-0.12),P=0.005],and adverse reaction rate[RR=0.21,95%CI(0.15,0.29),P=0.000]of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group.The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group[RR=1.14,95%CI(1.03,1.26),P<0.05].The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group[SMD=-0.60,95%CI(-0.96,-0.25),P<0.05].There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate.Based on the effective rate,the comparison between the HLWDD alone group and the western medicine group[RR=1.09,95%CI(1.00,-1.20)P<0.05],and between the HLWDD combined with western medicine group and the western medicine group[RR=1.15,95%CI(1.03,1.29),P<0.05]was the same.PSQI score[SMD=-0.44,95%CI(-0.59,-0.30),P<0.05]and TCM syndrome score[SMD=-1.10,95%CI(-1.59,-0.61),P<0.05]of HLWDD combined with western medicine group were significantly lower than those of the western medicine group.There were no significant differences of adverse reaction rate between HLWDD alone group[RR=0.08,95%CI(0.04,0.17),P<0.05]and HLWDD combined with western medicine group[RR=0.36,95%CI(0.24,0.53),P<0.05].Conclusion HLWDD alone or combined with western medicine is an effective treatment for insomnia caused by phlegm-heat internal disturbance,which has a high effective rate,significantly reduced PSQI score and TCM syndrome score,and favorable safety.The best course of treatment is 4 weeks.

Efficacy of Wendan Decoction series for coronary heart disease with anxiety and depression:A systematic review and meta-analysis

Objective:To systematically evaluate the clinical efficacy of Wendan Decoction series combined with conventional western medicine in the treatment of coronary heart disease complicated with anxiety and depression.Methods:We searched four Chinese databases including CNKI,WanFang,VIP,SinoMed,and five English databases of PubMed,Cochrane Library,Web of Science,EMBASE,Springer Link for clinical randomized controlled trials of using Wendan Decoction series in the treatment of coronary heart disease complicated with anxiety and depression.Time range for searching was from the establishment of these databases to January 2022.Then we screened the retrieved literature according to the inclusion and exclusion criteria,and conducted data extraction and quality evaluation of the selected literature.Meta analysis was conducted using RevMan 5.3 software.Results:A total of 13 RCT studies and 1007 patients with coronary heart disease complicated with anxiety and depression were included.Meta-analysis showed that Wendan Decoction series combined with conventional western medicine treatment showed better effects in the improvement rate of clinical anxiety[RR=1.21,95%CI=(1.12,1.31),P<0.00001],the improvement rate of depression[RR=1.30,95%CI=(1.10,1.53),P=0.002],the improvement rate of angina pectoris[RR=1.28,95%CI=(1.13,1.44),P<0.0001],increasing the ECG improvement rate[RR=1.29,95%CI=(1.07,1.55),P=0.008],increasing the rate of reducing nitroglycerin usage[RR=1.68,95%CI=(1.25,2.25,P=0.0006],as well as increasing the improvement rate of TCM symptoms[RR=1.15,95%CI=(1.04,1.26),P=0.004].It also showed better effects in reducing clinical anxiety and depression scores(SAS,SDS,HAMA,HAMD),SAQ scores and TCM symptom scores.The differences were statistically significant.Conclusion:Wendan Decoction series combined with conventional western medicine shows advantages in treating coronary heart disease patients complicated with anxiety and depression in reducing the angina pectoris score,anxiety and depression score,as well as improving the clinical TCM symptoms.

Linggui Zhugan Decoction Improves High Glucose-Induced Autophagy in Podocytes

Objective To explore the influence of Linggui Zhugan Decoction(LGZGD) on high glucose induced podocyte autophagy.Methods LGZGD containing serum was prepared by intragastric administation of 4.2 g/kg(low dose), 8.4 g/kg(medium dose), and 12.6 g/kg(high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 podocyte cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Both podocytes were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using Western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8/13 cells in the high glucose group slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the better effect(P < 0.05). Flow cytometry showed that the medium dose LGZGD group had a significantly lower apoptosis rate(P < 0.05) and higher survival rate(P > 0.05) compared to the high dose LGZGD group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to G2 phase. High dose LGZGD significanly reduced high glucose-increased autophagosome formation in both podocytes(P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3II/I, and P62 expressions were increased in MPC5 cells treated with high glucose and reversed after adminstration of low and medium doses of LGZGD(P < 0.05).Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.

Clinical Study of Shentong Zhuyu Decoction Combined with Massage Therapy in the Treatment of Exertional Chronic Lumbar Muscle Strain

[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle strain were randomly divided into two groups(32 cases each group).The patients in the control group only took celecoxib capsules,and those in the treatment group additionally took Shentong Zhuyu decoction combined with massage therapy.TCM syndrome score,lumbar function,hemorrheology index and clinical effect were compared between the two groups before and after treatment.[Results]After treatment,the TCM syndrome scores of lumbar distension/dull pain,tingling-like lumbago,adverse lateral turn,body weight loss,dark purple tongue,slow or astringent pulse,and Oswestry disability index(ODI)score in the treatment group were lower than those in the control group,and the levels of plasma viscosity,red blood cell aggregation index,platelet aggregation rate(PAG)and fibrinogen(Fib)were lower than those in the control group,showing statistical significance(P<0.05).The overall clinical effect distribution of the treatment group was better than that of the control group,and the difference was statistically significant(P<0.05).[Conclusions]Shentong Zhuyu decoction combined with massage therapy can effectively relieve the symptoms of patients with lumbago and improve the lumbar mobility function and hemorrheology,with obvious therapeutic effects in the treatment of exertional chronic lumbar muscle strain.

Pharmacodynamic Experiment of Dachengqi Decoction and Separated Decoction on Incomplete Intestinal Obstruction in Rats

[Objectives]To investigate the effect and mechanism of Dachengqi Decoction and separated decoction on incomplete intestinal obstruction in rats.[Methods]80 healthy SD rats were selected to establish incomplete intestinal obstruction model by silk ligation.The dosage was 20 mL/kg for 3 d,and the damage index of ileocecal mucosa was analyzed;the morphology of ileocecal mucosa was observed by HE staining;the serum levels of IL-1α,IL-1β,IL-6,IL-18,Ach,NO,ET,IL-1,TNF-αand ultra-micro Na+-K+-ATPase were detected by ELISA.[Results]Compared with the model group,the mucosal damage index of Dachengqi Decoction and each separated decoction group decreased significantly(P<0.05);compared with the normal group and sham operation group,the serum level of IL-1,IL-6,TNF-αand other factors in the model group increased significantly(P<0.05);compared with the model group,the serum IL-1,IL-6 and TNF-αsecretion levels of rats in Dachengqi Decoction group and separated decoction group decreased(P<0.01).[Conclusions]Dachengqi Decoction and each separated decoction can effectively improve intestinal tissue pathological damage in the incomplete intestinal obstruction model rats,and reduce the inflammatory reaction in the rat body.

Introduction of Western Medicines into China and Improvement on Decoctions during Modern China

During the late Qing dynasty(1840 A.D.-1912 A.D.),a large quantity of Western medicines entered China,which continuously impacted the traditional Chinese medicine(TCM)market and revealed the shortcomings of Chinese medicines.Some personages in the TCM community followed the trend of learning from the West,and attempted to reform TCM,with the improvement on decoction becoming an important aspect of this effort.Through debates and trials,the improvement on decoction underwent three stages of conceptual evolution:“taking Chinese medicines as the foundation and referring to the dosage forms of Western medicines”,“introducing Western techniques to serve the preparation of decoctions”and“integrating the theories of TCM and Western medicine to improve decoctions”.The study highlights the effective complementarity between modern TCM and Western medicine in the field of pharmacy,and provides valuable experience and support for the reevaluation of the value of TCM in contemporary society.

iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet

Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Meta-analysis of the efficacy and safety of Bushen Huoxue decoction in the treatment of Osteoporosis

Objective:To systematically evaluate the long-term efficacy of Bushen Huoxue Decoction combined with vertebroplasty(PVP or PKP)in the treatment of osteoporotic vertebral compression fractures(OVCF),in order to provide evidence-based reference for clinical application.Methods:To ensure the novelty of research data,a computer search was conducted between 2017 and February 2023 to publicly publish all randomized controlled studies and clinical trials at home and abroad on the treatment of OVCF with Bushen Huoxue Decoction combined with vertebroplasty published in CNKI,Wanfang,Vip,PubMed,CBM,and Cochrane libraries.Two researchers independently conducted literature screening and data extraction,evaluated the quality of randomized controlled trials included one by one according to the Cochrane collaboration network standards,and conducted a meta statistical analysis using RevMan5.3 for studies that met the inclusion criteria.Results:A total of 684 patients were included in 7 randomized controlled trials,including 342 patients in the observation group and 342 patients in the control group,with a ratio of 1:1;The meta-analysis results showed that in the observation group,the overall effective rate[RR=1.30,95%CI(1.14,1.47),P<0.001],visual analog pain(VAS)score[SMD=1.19,95%CI(0.77,1.61),P<0.0001],bone mineral density score[SMD=1.09,95%CI(0.15,2.04),P=0.02],COQOL score[SMD=0.99,95%CI(0.68,1.30),P<0.00001],OPG score[SMD=0.48,95%CI(0.18,0.77),P=0.002]The RANKL score[SMD=1.33,95%CI(1.00,1.65),P<0.0001]was significantly superior to the control group,with statistically significant differences.There was no significant difference in the Oswestry Disability Index(ODI)score[SMD=0.27,95%CI(-0.03,0.57),P=0.08],Cobb score[SMD=1.52,95%CI(-1.05,4.09),P=0.25],and vertebral height score[SMD=0.43,95%CI(-0.14,1.01),P=0.14].Conclusion:The results show that Bushen Huoxue Decoction combined with vertebroplasty has significant advantages in improving bone mineral density and alleviating pain in patients after OVCF,which is significantly superior to using OVCF alone.

Differential expression of miRNA in THP-1-derived foam cell model induced by drug-containing serum of Yimaijiangzhi decoction

Objective: To investigate the differential expression of miRNA and related biological functions and signaling pathways after the intervention of the THP-1-derived foam cell model with the drug-containing serum of Yimaijiangzhi Decoction. Methods: The experiment was divided into macrophage group, foam cell model group and Yimaijiangzhi drug-containing serum group. THP-1 cells were induced into macrophages by Fopol ester, and induced differentiated macrophages were given ox-LDL to establish foam cell model, and Yimaijiangzhi decoction rat serum was used to intervene the foam cells. Total RNA was extracted from cells in each group for miRNA sequencing, differential expression of miRNA was screened, and relevant target genes were predicted for GO analysis and KEGG analysis, protein interaction network and miRNA-target gene interaction network were established, and RT-qPCR was used to verify the possible signaling pathways for improving atherosclerosis. Result: The difference miRNA between blank group and model group was hsa-miR-302c-3p, hsa-miR-302d-3p, hsa- mir-30d-3p, hsa-mir-3189-3p, hsa-mir-374b-5p, hsa-mir-423-5p, hsa-mir-423-5p, and hsa- mir-4781-3p, hsa-mir-663a;The miRNAs of model group and Yimaijiangzhi drug-containing serum group were hsa-mir-3150a-3p, hsa-mir-7704, hsa-mir-887-3p, hsa-mir-150-5p, hsa- mir-423-5p, hsa-mir-374c-3p, hsa-mir-374c-3p, hsa-mir-374b-5p;The difference of miRNAs prediction target genes between model group and Yimaijiangzhi drug-containing serum group showed that the miRNA prediction target genes were mainly enriched in MAPK signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Wnt signaling pathway and other signaling pathways. SCN1A, PRKACA, MECP2, EIF4E, SRSF1, MBNL1, PRKCA, PPARGC1A may be the potential key targets for the effect of the drug-containing serum of Yimaijiangzhi Decoction on THP-1-derived foam cells. Conclusion: hsa-mir-374c-3p, hsa- mir-423-5p, and hsa-mir-374b-5p are important miRNAs that the drug-containing serum of Yimaijiangzhi Decoction acts on foam cells. The significantly differentially expressed mirnas and significantly enriched related signaling pathways may provide new ideas for the diagnosis and treatment of atherosclerosis.

Evaluation of the famous classic formula Sanhua decoction based on network pharmacology and multi-component quantitative analysis

Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.

A Preliminary Mechanism Study on the Treatment of Rabbit Bone Defect Bone Nonunion with Xuduan Jiegu Decoction

Objective: To investigate the curative effect and mechanism of Xuduan Jiegu Decoction in the treatment of rabbit bone defect bone nonunion. Methods: The experiment was randomly divided into three groups;1) The control group that was given neither the modeling nor the treatment;2) The model group that was not given the treatment after the operation to model a bone defect;3) The treatment group that was given intermittent bone decoction after modeling (i.e., the operation), the dose was 105 g/piece, twice a day, for 4 consecutive weeks. For the three groups, Anterolateral X-rays of the left forearm were taken 14 days after the surgery to observe the bone nonunion healing with pretherapy and post-treatment. The expression levels of TGF-β, BMP-2 and VEGF in the blood of each group were measured by ELISA at 4 weeks after treatment. The peri-fracture histopathological changes between each group of pretherapy and post-treatment were evaluated by using tissue sections. Results: Compared with the control group, there was no obvious healing in the model group on the 14th day after the operation. Compared with the model group, the treatment group was treated with Xuduan Jiegu Decoction, and there was a trend of healing and callus formation on the 14th day. HE staining showed that the cells in the control group were closely arranged without any pathological changes. In the model group, the tissues around the fracture end were arranged loosely, and the cells were vacuolated and infiltrated by inflammatory cells. Compared with the model group, the peripheral cell arrangement was better and the peripheral lesions were reduced in the treatment group. The content of TGF-β, BMP-2 and VEGF in blood detected by ELISA was significantly higher in the treatment group than in the control group and the model group, with statistical significance. Conclusion: Xuduan Jiegu Decoction can promote callus formation and accelerate fracture healing in rabbit radius bone defect, and the mechanism of promoting fracture healing is related to the increases of TGF-β, BMP-2 and VEGF levels.

Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury

Objective:To explore the effects of Buyang Huanwu decoction(BYHWD)on vascular neogenesis and hemorheological parameters following cervical spinal cord injury(SCI).Methods:An acute cervical SCI model was established using 84 female SpragueeDawley rats.Functional recovery of the rats was evaluated using the forelimb locomotor scale score,forelimb grip strength test,and Basso-Beattie-Bresnahan score.The animals were subsequently euthanized at days 7 and 28 post-operatively.The gross morphology,neuronal survival,and myelin sheath in the injured area were evaluated using hematoxylin and eosin(HE),Nissl,and luxol fast blue(LFB)staining,respectively.Immunofluorescence staining was used to observe CD31 expression 7 days post-injury.Furthermore,the expression of CD31,neuronal nuclear protein(NeuN),and myelin basic protein(MBP)were evaluated 28 days post-injury.Additionally,vascular endothelial growth factor A(VEGFA)and VEGF receptor-2(VEGFR-2)expression was evaluated using western blotting.Whole-blood viscosity,plasma viscosity,and red blood cell aggregation were measured using a hemorheometer.Results:From postoperative days 3e28,motor function in the BYHWD group began to recover consid-erably compared to the SCI group.BYHWD effectively restored spinal cord histopathology.In addition,the number of NeuN-positive cells,and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group(all P<0.05).Moreover,this decoction significantly upregulated the expression of VEGFA and VEGFR-2(all P<0.05).BYHWD improved the hemorheology results(i.e.,except erythrocyte aggregation index in the low-dose group),revealing statistically significant differences compared with the SCI group(all P<0.05).Conclusion:BYHWD effectively promoted angiogenesis,improved hemorheological parameters,and protected neurons and myelin sheaths,ultimately promoting the recovery of neurological function after cervical SCI in rats.These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.