Objective:To explore the improvement effect of implementing Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction on cardiac function and quality of life of patients during the treatment of coronary heart disease...Objective:To explore the improvement effect of implementing Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction on cardiac function and quality of life of patients during the treatment of coronary heart disease complicated with heart failure.Methods:Eighty cases were included in the study,and they were equally divided into a control group(n=40,treated with basic western medicine)and a study group(n=40,treated with Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction)according to random sampling grouping method.The intervention index results of the two groups were compared.Results:The improvement of cardiac function index,TCM syndrome score,and quality of life in the study group was more prominent,with a statistical value of P<0.05.Conclusion:Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction and conventional western medicine treatment can effectively improve the cardiac function of patients with coronary heart disease complicated with heart failure and enhance their quality of life.It is worthy of clinical promotion and application.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
Traditional Chinese medicine has unique advantages in preventing and treating COVID-19,and Fuzheng Jiedu decoction(FZJDD)was reported to be effective against COVID-19 in clinical trials.To investigate the potential me...Traditional Chinese medicine has unique advantages in preventing and treating COVID-19,and Fuzheng Jiedu decoction(FZJDD)was reported to be effective against COVID-19 in clinical trials.To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2,we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD.Interestingly,FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-23CLpro.Moreover,FZJDD can regulate the TNF and the MAPK signaling pathway to inhibit the inflammatory response and alleviate the“cytokine storm”.A total of 298 compounds were identified in FZJDD,among them,caffeic acid and octyl gallate were found to be the potential therapeutic agents of FZJDD.Importantly,FZJDD can broadly inhibit coronavirus infection,including SADS-CoV and porcine epidemic diarrhea virus(PEDV)live viruses,SARS-CoV,MERS-CoV,and SARS-CoV-2 mutant pseudotyped viruses,which might be ascribed to the broad-spectrum anti-coronavirus activity of caffeic acid and octyl gallate.In conclusion,this study reveals the mechanisms and material basis of FZJDD against SARS-CoV-2 and identifies the broadspectrum anti-coronavirus activity of FZJDD for the first time.Our data provide empirical evidence for the development and application of FZJDD.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.展开更多
Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mec...Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.展开更多
The classified prescriptions from Chaihu decoction have been widely used in ancient and modern times.In spite of many previous research studies,the extensiveness and diversity of their applications have not been syste...The classified prescriptions from Chaihu decoction have been widely used in ancient and modern times.In spite of many previous research studies,the extensiveness and diversity of their applications have not been systematically studied.The author applied Chaihu Wendan decoction to treat phlegm and qi stagnation in the middle energizer,applied Chaihu Guizhi decoction to treat simultaneous disease of Shaoyang and Taiyang,applied Chaihu Xiexin decoction to treat simultaneous disease of the spleen,stomach,liver,and gallbladder,applied Chaihu Ermiao powder to treat simultaneous disease of hand Shaoyang and foot Taiyin,applied Chaihu Erchen decoction to treat simultaneous disease of Shaoyang and Taiyin,applied Chailing decoction to treat simultaneous disease of hand Shaoyin and foot Taiyang,applied Chaihu Guizhi Ganjiang decoction to treat Shaoyang and Taiyin cold fluid retention and heat stagnation syndrome of Shaoyang complicated with Taiyin,applied Chaihu Xingren decoction to treat simultaneous disease of hand Shaoyang and hand Taiyin,applied Chaihu Sanren decoction to treat the disease caused by damp-heat stagnation in the hand Shaoyang and the foot Taiyin,and applied Chaihu Ganlu Xiaodu pellet to treat the diseases of hand Shaoyang and foot Yangming.The effects were all remarkable.展开更多
Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in manag...Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.展开更多
Objectives:Irinotecan(CPT-11)-induced delayed diarrhea is a major dose-limiting toxicity that restricts its clinical application.Gegen Qinlian decoction(GQD),a traditional Chinese herbal formula,has shown potential in...Objectives:Irinotecan(CPT-11)-induced delayed diarrhea is a major dose-limiting toxicity that restricts its clinical application.Gegen Qinlian decoction(GQD),a traditional Chinese herbal formula,has shown potential in alleviating CPT-11-induced intestinal injury,but its underlying mechanisms remain incompletely understood.This study aimed to systematically elucidate the protective effects and mechanisms of GQD against CPT-11 enterotoxicity.Methods:We integrated ultra-performance liquid chromatography-quadrupole-Orbitrap-mass spectrometry(UPLC-QE-Orbitrap-MS)for chemical profiling of GQD,along with network pharmacology,molecular docking,and molecular dynamics simulation to identify key bioactive constituents and potential targets.Furthermore,a CPT-11-treated mouse model and Caco-2 cell monolayers were employed to evaluate the effects of GQD.Quantitative proteomics and untargeted metabolomics were applied to explore pathway alterations,and biochemical,histological,and functional analyses were conducted to assess inflammatory responses,oxidative stress,barrier integrity,and drug transporter activity.Results:A total of 65 compounds were identified in GQD,with 17 prioritized as putative bioactive constituents.Network analysis highlighted the IL-6/IL-22/STAT3 inflammatory axis and ABC transporter pathways as central mechanisms.In vivo,GQD administration ameliorated diarrhea,preserved colonic architecture and mucin production,reduced pro-inflammatory cytokines and oxidative stress,and restored expression of tight-junction proteins.Multi-omics integration showed that GQD counteracted CPT-11-induced dysregulation in complement/coagulation cascades and metabolic pathways,while enriching ABC transporter-related functions.In Caco-2 monolayers,GQD promoted SN-38 efflux,upregulated MDR1 and MRP2 expression,and decreased intracellular SN-38 accumulation.Consistent with this,GQD enhanced colonic clearance of SN-38 in mice.Conclusions:GQD protects against CPT-11-induced enterotoxicity primarily through two mechanisms:suppressing the pro-inflammatory IL-6/IL-22/STAT3 signaling pathway and enhancing the epithelial efflux of SN-38 via upregulation of ABC transporters.These findings provide a mechanistic basis for the potential use of GQD as an adjuvant therapy to mitigate intestinal toxicity during irinotecan chemotherapy.展开更多
BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial...BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.展开更多
Objective This study aimed to study the effects of different crystalline states of Sheng Shigao(raw gypsum,RG)and its inorganic elements on the antipyretic efficacy of Baihu Decoction(BHT).Methods RG samples calcined ...Objective This study aimed to study the effects of different crystalline states of Sheng Shigao(raw gypsum,RG)and its inorganic elements on the antipyretic efficacy of Baihu Decoction(BHT).Methods RG samples calcined at different temperatures were prepared.The phase composition of RG and Duan Shigao(calcination of gypsum,CG)as well as the changes in phase composition before and after adding water to RG calcined at specific temperatures,were determined using X-ray diffraction(XRD).A fever model was established by subcutaneously injecting 20%yeast suspension(10 mL·kg~(-1))into the backs of rats.The effects of BHT containing RG in different crystalline states on rat body temperature were measured.Serum levels of IL-1β,IL-6,and hypothalamic prostaglandin E2(PGE_2)were detected using ELISA.Serum Ca~(2+)levels were measured using a microplate method.The content of trace elements in RG and CG and the corresponding freeze-dried BHT powder was determined using inductively coupled plasma mass spectrometry(ICP-MS).The complexation of representative inorganic elements with mangiferin,a major active component in BHT,was investigated using UV-Vis spectroscopy and fluorescence spectroscopy.A validation model was established using RAW264.7 mouse macrophages.Drug-containing serum of BHT with different inorganic elements was prepared,and the nitric oxide(NO)levels in the cell supernatant of different treatment groups were measured using the Griess method.The mRNA levels of IL-6,TNF-α,and PGE2in each group were detected using qPCR(real-time fluorescent quantitative PCR).Results After calcination,the phase composition of RG changed,and the content of inorganic elements in RG,CG170(RG calcined at 170°C),and CG350(RG calcined at 350°C)showed similar trends.Compared with RG,the content of Ca,Sr,Al,and Na in CG changed significantly.Compared with BHT,the content of Ca,Sr,Si,and Na in CG changed significantly when incorporated into the formula.Intermolecular interactions confirmed strong binding between mangiferin and Cu~(2+)and Al~(3+).Cu~(2+)and Fe~(3+)exhibited fluorescence quenching effects on mangiferin solution,while Al~(3+)and Zn~(2+)showed strong fluorescence enhancement,with fluorescence intensity increasing by 120-fold and 30-fold,respectively.In vitro evaluation of synergistic anti-inflammatory effects confirmed that Ca,Fe,Cr,Al,and Si exhibited synergistic anti-inflammatory effects.Conclusion The crystalline state of RG has little effect on its antipyretic properties,while Ca,Sr,Na,Fe,and Al are likely the key material bases influencing its efficacy.展开更多
Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely li...Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.展开更多
Objective:To investigate the clinical efficacy of Xiaochaihu Decoction combined with Xiaoxianxiong Decoction in the treatment of post-stroke pneumonia.Methods:To complete the sample grouping comparison,all patients wi...Objective:To investigate the clinical efficacy of Xiaochaihu Decoction combined with Xiaoxianxiong Decoction in the treatment of post-stroke pneumonia.Methods:To complete the sample grouping comparison,all patients with post-stroke pneumonia were investigated,and the number of cases was 60.These patients’diseases were consistent with the dialectical standards of traditional Chinese medicine(phlegm-heat obstructing lungs).The patients were randomly divided into a control group(30 cases,treated with antibiotics and symptomatic methods)and a treatment group(30 cases,treated with Xiaochaihu Decoction and Xiaoxianxiong Decoction on the basis of the control group).Various indicators were compared.Results:The total clinical effective rates were 93%and 80%in the treatment group and the control group,respectively,with statistical significance(P<0.05).The improvement of various clinical symptoms was compared,and the values in the treatment group were reduced,showing significance(P<0.05).Analysis of serum factor indicators showed that the overall trend of the treatment group was reduced,and the comparison between groups was below 0.05.Conclusion:Xiaochaihu Decoction combined with Xiaoxianxiong Decoction has a significant clinical effect in the treatment of post-stroke pneumonia(phlegm-heat obstructing lungs syndrome),which can reduce inflammatory reactions and has few adverse reactions,worthy of clinical application.展开更多
BACKGROUND In China Banxia Xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years.BXD has been shown to reverse GC histopathology,but its chemical composition and action mechanism are ...BACKGROUND In China Banxia Xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years.BXD has been shown to reverse GC histopathology,but its chemical composition and action mechanism are still unknown.AIM To investigate the mechanism of BXD against GC based on utilizing transcrip-tomics and proteomics techniques experiments.METHODS Using the AGS cell line as the model group,the Cell Counting Kit-8 method and Annexin V-AbFluor™were employed 488/propidium iodide double staining method was used to detect the levels of cell proliferation and apoptosis.Differ-ential expression genes and differentially expressed proteins before and after BXD intervention were detected using RNA-seq and Pro DIA techniques.Key tran-scription factors were identified by enrichment and analysis using Metascape,and the key pathways were validated by western blot and reverse transcription PCR in vitro and in vivo experiments.RESULTS BXD significantly inhibited the proliferation rate and migration rate of GC cells and promoted cell apoptosis.The comprehensive analysis of transcriptomics and proteomics showed that five transcription factors,namely phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,phosphoinositide-3-kinase regulatory subunit 1,AKT serine/threonine kinase 1,heat shock protein 90 alpha family class A member 1,and tumor protein p53,were key factors in BXD-mediated anti-cancer therapy and participated in the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway.In vitro experiments were conducted using LY294002,an inhibitor of the PI3K/AKT signaling pathway,to validate the expression of five transcription factors at the protein and mRNA levels.In vivo experiments have shown that BXD inhibits tumor growth and suppresses the expression of the PI3K/AKT signaling pathway.CONCLUSION Transcriptomic and proteomic analysis showed that BXD inhibited tumor growth and slowed cancer progression by suppressing five factors in the PI3K/AKT signaling pathway,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,phosphoinositide-3-kinase regulatory subunit 1,and AKT serine/threonine kinase 1.展开更多
Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CR...Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.展开更多
Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analys...Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.展开更多
Hypertension is one of the most prevalent cardiovascular diseases,and autophagy is known to play a significant role in the pathogenesis and progression of cardiovascular conditions.This study aimed to evaluate the eff...Hypertension is one of the most prevalent cardiovascular diseases,and autophagy is known to play a significant role in the pathogenesis and progression of cardiovascular conditions.This study aimed to evaluate the effects of Huanglian Jiedu decoction(HLJDD)on myocardial mitochondrial autophagy in spontaneously hypertensive rats(SHRs)and to further explore the relationship between autophagy,myocardial remodeling,and injury.The SHRs were randomly assigned to five groups:the model group,the HLJDD low-dose group,the HLJDD medium-dose group,the HLJDD high-dose group,and a positive control group treated with captopril.Additionally,a blank control group was established using Wistar Kyoto(WKY)rats,with 10 rats in each group.The model and blank control groups were administered an equivalent volume of physiological saline via oral gavage,while the treatment groups received their respective doses of HLJDD or captopril by oral gavage.Following the treatments,various parameters were assessed,including blood pressure(systolic,diastolic,and mean arterial pressure),mitochondrial swelling and membrane potential,free ATPase activity,as well as the mRNA and protein levels of autophagy-related factors.The results showed that HLJDD significantly reduced blood pressure(systolic,diastolic,and mean arterial pressure)in SHR rats.Moreover,it enhanced mitochondrial swelling and membrane potential,increased mitochondrial ATPase activity,and decreased the mRNA and protein expression levels of autophagy-related genes(AKT,mTOR,Beclin-1,and LC3-II)in SHRs.The findings of this study suggested that HLJDD could effectively ameliorate myocardial tissue injury in SHRs,and its protective effects on the heart might be attributed to the reduction of autophagy in cardiomyocyte mitochondria.This provided insights into the potential therapeutic use of HLJDD in managing hypertension-induced myocardial injury and remodeling.展开更多
Background:The traditional Chinese medicine compound Sancao decoction(SCD)is a folk prescription for regulating immunity.It is composed of 8 Chinese herbal medicines,such as Prunellae Spica(Xiakucao),Houttuyniae Herba...Background:The traditional Chinese medicine compound Sancao decoction(SCD)is a folk prescription for regulating immunity.It is composed of 8 Chinese herbal medicines,such as Prunellae Spica(Xiakucao),Houttuyniae Herba(Yuxingcao),Lysimachiae Herba(Jinqiancao)and so on.In cancer,the interleukin-6(IL-6)/the signal transducer and the activator of transcription 3(STAT3)pathway directly promotes the proliferation,survival and angiogenesis of cancer cells,and arginase-1(ARG-1)is a key enzyme for myeloid-derived suppressor cells(MDSCs)to exert immunosuppressive function.It is not clear whether SCD regulates the expression of ARG-1 in MDSCs through the IL-6/STAT3 pathway.Therefore,we explored the effect and mechanism of SCD on lung metastasis of breast cancer.Methods:The components in SCD have been analyzed by HPLC-MS.A spontaneous metastasis model of breast cancer was established by injecting 4T1 cells into the mammary fat pad of BALB/c mice.Pre-metastatic niche(PMN)formation and the role of SCD on PMN were evaluated by lung metastasis nodules,lung pathology tests and immunofluorescence for 2–4 weeks.Serum tests and hematoxylin-eosin staining(H&E)were used to evaluate the side effects of cisplatin.Western blot and ELISA were used to detect proteins and cytokines of the STAT3 signaling pathway in mouse lung tissue.Results:Compared with SCD or cisplatin treatment alone,SCD/cisplatin(CP)synergistic administration not only significantly inhibited orthotropic breast tumor growth,but also reduced lung metastasis and alleviated the hepatorenal toxicity induced by CP in vivo.Remarkably,the combination effectively inhibited PMN formation and the accumulation of MDSCs in the lung PMN,accompanied by the significant infiltration of CD4+T and CD8+T-lymphocytes in the lung PMN and spleen.In addition,the SCD/CP combination downregulated protein expression levels of STAT3,p-STAT3,IL-6 and ARG-1 in the lung PMN of breast cancer mice.Conclusion:The synergistic effect of SCD and cisplatin inhibited MDSCs aggregation and the immunosuppressive function of pulmonary PMN,thereby remodeling the immunosuppressive tumor microenvironment and enhancing anti-tumor immunity,leading to remission of orthotopic breast cancer and lung metastases and amelioration of cisplatin-induced liver and kidney toxicity.展开更多
Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat ...Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.展开更多
Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limite...Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.展开更多
Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of med...Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of medical treatments in its treatment and the increasing incidence of lung cancer.Traditional Chinese medicine plays an important role in the prevention and treatment of lung cancer.We used network pharmacology to investigate and predict the targets and associated signaling pathways of Wen-Yang-Hua-Liu Decoction(WYHLD)for the treatment of NSCLC.In addition,we investigated the growth mechanism of WYHLD on NSCLC by observing the effects of WYHLD on the processes of NSCLC proliferation,apoptosis,and ferroptosis.Methods:WYHLD drugs were obtained from the TCMSP database and potential targets from the Swiss Target Prediction and Uniprot databases;NSCLC-related genes were collected from the Genecards database;and the intersection genes of WYHLD and NSCLC were obtained from the Venny2.1 platform and imported into the STRING database.The intersection genes of WYHLD and NSCLC were collected from the Genecards database,imported into the STRING database,constructed into a into a protein-protein interaction network(PPI),visualized by Cytoscape 3.9.1 software,and analysed by GO enrichment and KEGG pathway analysis using the Metascape database to predict the direct targets and signaling pathways of WYHLD in the treatment of NSCLC.The NSCLC cell line A549 was cultured,and CCK-8 and wound healing assays were performed to assess cell proliferation and migration.Apoptosis was detected by Hoechst staining.Reactive oxygen species(ROS)levels were measured using flow cytometry.The microstructure of A549 cells observed by transmission electron microscopy.In addition,Western blot was performed to detect MYC,VEGF,HIF-1α,β-catenin,Cleaved-caspase3,GPX4,and SLC7A11 protein expression.Results:The network pharmacological analysis identified 160 WYHLD compounds,1,444 NSCLC disease-related targets,and 133 overlapping WYHLD and NSCLC targets.MYC,AKT1,JUN,ESR1,FOS,TP53,BCL2,and other proteins with high degree values were ranked as therapeutic targets in the STRING 11.0 database.The enriched pathways were identified as being associated with the cancer pathway,the AGE-RAGE signaling pathway,and NSCLC.In in vitro experiments,we found that WYHLD inhibited the migration and proliferation of NSCLC cells and promoted their apoptosis.Analysis of reactive oxygen species showed that WYHLD could promote cellular production of reactive oxygen species.In addition,WYHLD significantly suppressed the expression of MYC,GPX4,SLC7A11,β-catenin,and VEGF while increasing the expression of Cleaved-caspase3.Conclusion:Our results suggest that WYHLD may act as a novel strategy for the prevention and treatment of lung cancer by targeting the Wnt pathway,thereby inhibiting the growth mechanism of NSCLC.展开更多
文摘Objective:To explore the improvement effect of implementing Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction on cardiac function and quality of life of patients during the treatment of coronary heart disease complicated with heart failure.Methods:Eighty cases were included in the study,and they were equally divided into a control group(n=40,treated with basic western medicine)and a study group(n=40,treated with Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction)according to random sampling grouping method.The intervention index results of the two groups were compared.Results:The improvement of cardiac function index,TCM syndrome score,and quality of life in the study group was more prominent,with a statistical value of P<0.05.Conclusion:Buzhong Yiqi Decoction combined with Xuefu Zhuyu Decoction and conventional western medicine treatment can effectively improve the cardiac function of patients with coronary heart disease complicated with heart failure and enhance their quality of life.It is worthy of clinical promotion and application.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
基金supported by National Key Research and Development Program of China(grant No.2022YFC0867500,2020YFA0712102)National Natural Science Foundation of China(grant No.82151224,82202492)+3 种基金Fundamental Research Funds for Central Universities(grant No.QNTD 2023-01)Nutrition and Care of Maternal&Child Research Project of Biostime Institute of Nutrition&Care(grant No.2023BINCMCF28)State Key Laboratory of Pathogen and Biosecurity of China(grant No.SKLPBS2438)State Key Laboratory of Component-based Chinese Medicine(grant No.CBCM2024204).
文摘Traditional Chinese medicine has unique advantages in preventing and treating COVID-19,and Fuzheng Jiedu decoction(FZJDD)was reported to be effective against COVID-19 in clinical trials.To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2,we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD.Interestingly,FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-23CLpro.Moreover,FZJDD can regulate the TNF and the MAPK signaling pathway to inhibit the inflammatory response and alleviate the“cytokine storm”.A total of 298 compounds were identified in FZJDD,among them,caffeic acid and octyl gallate were found to be the potential therapeutic agents of FZJDD.Importantly,FZJDD can broadly inhibit coronavirus infection,including SADS-CoV and porcine epidemic diarrhea virus(PEDV)live viruses,SARS-CoV,MERS-CoV,and SARS-CoV-2 mutant pseudotyped viruses,which might be ascribed to the broad-spectrum anti-coronavirus activity of caffeic acid and octyl gallate.In conclusion,this study reveals the mechanisms and material basis of FZJDD against SARS-CoV-2 and identifies the broadspectrum anti-coronavirus activity of FZJDD for the first time.Our data provide empirical evidence for the development and application of FZJDD.
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
基金supported by the National Natural Science Foundation of China(No.82074054)Shanghai Municipal Commission of Health and Family Planning(No.ZY(2021-2023)-0208)+2 种基金Youth Program of the National Natural Science Foundation of China(No.81903831)Shanghai Municipality:Shanghai Chenguang Program(No.19CG48)Natural Science Foundation of Shanghai(No.24ZR1465900)。
文摘Lingguizhugan Decoction(LGZG)demonstrates significant efficacy in treating various cardiovascular diseases clinically,yet its precise mechanism of action remains elusive.This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol(ISO)continuous stimulation-induced chronic heart failure(CHF)in mice,providing direct experimental evidence for further clinical applications.In vivo,continuous ISO infusion was administered to mice,and ventricular myocytes were utilized to explore LGZG's potential mechanism of action on theβ1-adrenergic receptor(β1-AR)/Gs/G protein-coupled receptor kinases(GRKs)/β-arrestin signaling deflection system in the heart.The findings reveal that LGZG significantly reduced the messenger ribonucleic acid(mRNA)expression of hypertrophy-related biomarkers[atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)]and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF.Furthermore,LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate(c AMP)/protein kinase A(PKA)signaling and downregulated the downstream transcriptional activity of c AMP-response element binding protein(CREB)and the expression of the coactivator CBP/P300.Notably,LGZG downregulated the expression ofβ-arrestin1 and GRK 2/3/5 while upregulating the expression ofβ1-AR andβ-arrestin2.These results suggest that LGZG inhibits Gs/c AMP/PKA signaling andβ-arrestin/GRK-mediated desensitization and internalization ofβ1-AR,potentially exerting cardioprotective effects through the synergistic regulation of theβ1-AR/Gs/GRKs/β-arrestin signaling deflection system via multiple pathways.
基金supported by Jiangxi Provincial Health Department Chinese Medicine Research Program Project{[2004]No.28}.
文摘The classified prescriptions from Chaihu decoction have been widely used in ancient and modern times.In spite of many previous research studies,the extensiveness and diversity of their applications have not been systematically studied.The author applied Chaihu Wendan decoction to treat phlegm and qi stagnation in the middle energizer,applied Chaihu Guizhi decoction to treat simultaneous disease of Shaoyang and Taiyang,applied Chaihu Xiexin decoction to treat simultaneous disease of the spleen,stomach,liver,and gallbladder,applied Chaihu Ermiao powder to treat simultaneous disease of hand Shaoyang and foot Taiyin,applied Chaihu Erchen decoction to treat simultaneous disease of Shaoyang and Taiyin,applied Chailing decoction to treat simultaneous disease of hand Shaoyin and foot Taiyang,applied Chaihu Guizhi Ganjiang decoction to treat Shaoyang and Taiyin cold fluid retention and heat stagnation syndrome of Shaoyang complicated with Taiyin,applied Chaihu Xingren decoction to treat simultaneous disease of hand Shaoyang and hand Taiyin,applied Chaihu Sanren decoction to treat the disease caused by damp-heat stagnation in the hand Shaoyang and the foot Taiyin,and applied Chaihu Ganlu Xiaodu pellet to treat the diseases of hand Shaoyang and foot Yangming.The effects were all remarkable.
基金supported by the Hebei Provincial Administration of Traditional Chinese Medicine 2022 Chinese medicine research program mandatory subject(2021.No.12)Hebei famous traditional Chinese medicine inheritance studio construction project(2024.No.37)Yunnan Fundamental Research Projects(grant No.202501AT070266).
文摘Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202209)the National Natural Science Foundation of China(NSFC)Youth Program(No.82405145)the National Postdoctoral Researcher Support Program Category C(No.GZC20230335).
文摘Objectives:Irinotecan(CPT-11)-induced delayed diarrhea is a major dose-limiting toxicity that restricts its clinical application.Gegen Qinlian decoction(GQD),a traditional Chinese herbal formula,has shown potential in alleviating CPT-11-induced intestinal injury,but its underlying mechanisms remain incompletely understood.This study aimed to systematically elucidate the protective effects and mechanisms of GQD against CPT-11 enterotoxicity.Methods:We integrated ultra-performance liquid chromatography-quadrupole-Orbitrap-mass spectrometry(UPLC-QE-Orbitrap-MS)for chemical profiling of GQD,along with network pharmacology,molecular docking,and molecular dynamics simulation to identify key bioactive constituents and potential targets.Furthermore,a CPT-11-treated mouse model and Caco-2 cell monolayers were employed to evaluate the effects of GQD.Quantitative proteomics and untargeted metabolomics were applied to explore pathway alterations,and biochemical,histological,and functional analyses were conducted to assess inflammatory responses,oxidative stress,barrier integrity,and drug transporter activity.Results:A total of 65 compounds were identified in GQD,with 17 prioritized as putative bioactive constituents.Network analysis highlighted the IL-6/IL-22/STAT3 inflammatory axis and ABC transporter pathways as central mechanisms.In vivo,GQD administration ameliorated diarrhea,preserved colonic architecture and mucin production,reduced pro-inflammatory cytokines and oxidative stress,and restored expression of tight-junction proteins.Multi-omics integration showed that GQD counteracted CPT-11-induced dysregulation in complement/coagulation cascades and metabolic pathways,while enriching ABC transporter-related functions.In Caco-2 monolayers,GQD promoted SN-38 efflux,upregulated MDR1 and MRP2 expression,and decreased intracellular SN-38 accumulation.Consistent with this,GQD enhanced colonic clearance of SN-38 in mice.Conclusions:GQD protects against CPT-11-induced enterotoxicity primarily through two mechanisms:suppressing the pro-inflammatory IL-6/IL-22/STAT3 signaling pathway and enhancing the epithelial efflux of SN-38 via upregulation of ABC transporters.These findings provide a mechanistic basis for the potential use of GQD as an adjuvant therapy to mitigate intestinal toxicity during irinotecan chemotherapy.
基金Supported by Liaoning Provincial Science and Technology Plan Joint Plan,No.2023JH2/101700149。
文摘BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.
基金Joint Fund Project of the Henan Provincial Science and Technology Research and Development Plan(222301420060)。
文摘Objective This study aimed to study the effects of different crystalline states of Sheng Shigao(raw gypsum,RG)and its inorganic elements on the antipyretic efficacy of Baihu Decoction(BHT).Methods RG samples calcined at different temperatures were prepared.The phase composition of RG and Duan Shigao(calcination of gypsum,CG)as well as the changes in phase composition before and after adding water to RG calcined at specific temperatures,were determined using X-ray diffraction(XRD).A fever model was established by subcutaneously injecting 20%yeast suspension(10 mL·kg~(-1))into the backs of rats.The effects of BHT containing RG in different crystalline states on rat body temperature were measured.Serum levels of IL-1β,IL-6,and hypothalamic prostaglandin E2(PGE_2)were detected using ELISA.Serum Ca~(2+)levels were measured using a microplate method.The content of trace elements in RG and CG and the corresponding freeze-dried BHT powder was determined using inductively coupled plasma mass spectrometry(ICP-MS).The complexation of representative inorganic elements with mangiferin,a major active component in BHT,was investigated using UV-Vis spectroscopy and fluorescence spectroscopy.A validation model was established using RAW264.7 mouse macrophages.Drug-containing serum of BHT with different inorganic elements was prepared,and the nitric oxide(NO)levels in the cell supernatant of different treatment groups were measured using the Griess method.The mRNA levels of IL-6,TNF-α,and PGE2in each group were detected using qPCR(real-time fluorescent quantitative PCR).Results After calcination,the phase composition of RG changed,and the content of inorganic elements in RG,CG170(RG calcined at 170°C),and CG350(RG calcined at 350°C)showed similar trends.Compared with RG,the content of Ca,Sr,Al,and Na in CG changed significantly.Compared with BHT,the content of Ca,Sr,Si,and Na in CG changed significantly when incorporated into the formula.Intermolecular interactions confirmed strong binding between mangiferin and Cu~(2+)and Al~(3+).Cu~(2+)and Fe~(3+)exhibited fluorescence quenching effects on mangiferin solution,while Al~(3+)and Zn~(2+)showed strong fluorescence enhancement,with fluorescence intensity increasing by 120-fold and 30-fold,respectively.In vitro evaluation of synergistic anti-inflammatory effects confirmed that Ca,Fe,Cr,Al,and Si exhibited synergistic anti-inflammatory effects.Conclusion The crystalline state of RG has little effect on its antipyretic properties,while Ca,Sr,Na,Fe,and Al are likely the key material bases influencing its efficacy.
基金supported by the National Natural Science Foundation of China(No.82360897)Natural Science Foundation of Jiangxi Province of China(No.20212BAB216007)Administration of Traditional Chinese Medicine of Jiangxi Province of China(No.2022A328).
文摘Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.
文摘Objective:To investigate the clinical efficacy of Xiaochaihu Decoction combined with Xiaoxianxiong Decoction in the treatment of post-stroke pneumonia.Methods:To complete the sample grouping comparison,all patients with post-stroke pneumonia were investigated,and the number of cases was 60.These patients’diseases were consistent with the dialectical standards of traditional Chinese medicine(phlegm-heat obstructing lungs).The patients were randomly divided into a control group(30 cases,treated with antibiotics and symptomatic methods)and a treatment group(30 cases,treated with Xiaochaihu Decoction and Xiaoxianxiong Decoction on the basis of the control group).Various indicators were compared.Results:The total clinical effective rates were 93%and 80%in the treatment group and the control group,respectively,with statistical significance(P<0.05).The improvement of various clinical symptoms was compared,and the values in the treatment group were reduced,showing significance(P<0.05).Analysis of serum factor indicators showed that the overall trend of the treatment group was reduced,and the comparison between groups was below 0.05.Conclusion:Xiaochaihu Decoction combined with Xiaoxianxiong Decoction has a significant clinical effect in the treatment of post-stroke pneumonia(phlegm-heat obstructing lungs syndrome),which can reduce inflammatory reactions and has few adverse reactions,worthy of clinical application.
基金Supported by the Key Program of Shandong Province,China,No.2016CYJS08A01-6.
文摘BACKGROUND In China Banxia Xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years.BXD has been shown to reverse GC histopathology,but its chemical composition and action mechanism are still unknown.AIM To investigate the mechanism of BXD against GC based on utilizing transcrip-tomics and proteomics techniques experiments.METHODS Using the AGS cell line as the model group,the Cell Counting Kit-8 method and Annexin V-AbFluor™were employed 488/propidium iodide double staining method was used to detect the levels of cell proliferation and apoptosis.Differ-ential expression genes and differentially expressed proteins before and after BXD intervention were detected using RNA-seq and Pro DIA techniques.Key tran-scription factors were identified by enrichment and analysis using Metascape,and the key pathways were validated by western blot and reverse transcription PCR in vitro and in vivo experiments.RESULTS BXD significantly inhibited the proliferation rate and migration rate of GC cells and promoted cell apoptosis.The comprehensive analysis of transcriptomics and proteomics showed that five transcription factors,namely phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,phosphoinositide-3-kinase regulatory subunit 1,AKT serine/threonine kinase 1,heat shock protein 90 alpha family class A member 1,and tumor protein p53,were key factors in BXD-mediated anti-cancer therapy and participated in the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway.In vitro experiments were conducted using LY294002,an inhibitor of the PI3K/AKT signaling pathway,to validate the expression of five transcription factors at the protein and mRNA levels.In vivo experiments have shown that BXD inhibits tumor growth and suppresses the expression of the PI3K/AKT signaling pathway.CONCLUSION Transcriptomic and proteomic analysis showed that BXD inhibited tumor growth and slowed cancer progression by suppressing five factors in the PI3K/AKT signaling pathway,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,phosphoinositide-3-kinase regulatory subunit 1,and AKT serine/threonine kinase 1.
基金supported by National Nature Science Foundation of China(Grant Nos.:82320108022,82322076,and 822104466)Shanghai Rising-Star Program,China(Grant No.:20QA1409300)+1 种基金the National Funding Program for Postdoctoral Researchers,China(C gradeProgram No.:GZC20231707).
文摘Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.
基金supported by the National Natural Science Foundation of China(No.82405237,82373835,82173781)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110768,2019A1515010806)+3 种基金Foshan Science and Technology Bureau’s self funded project(No.2320001007283)Key Field Projects(Intelligent Manufacturing)of General Universities in Guangdong Province(No.2020ZDZX2057)the Scientific Research Projects(Characteristic Innovation)of General Universities in Guangdong Province(No.2019KTSCX195)Guangdong Provincial Medical Research Foundation(No.A2022061).
文摘Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.
基金The Shandong Provincial Key Project of TCM Science and Technology(Grant Nos.M-2023170,M-2022233)the Binzhou Medical College Student Innovation and Entrepreneurship Training Program(Grant Nos.X202410440414,X2024225030120)。
文摘Hypertension is one of the most prevalent cardiovascular diseases,and autophagy is known to play a significant role in the pathogenesis and progression of cardiovascular conditions.This study aimed to evaluate the effects of Huanglian Jiedu decoction(HLJDD)on myocardial mitochondrial autophagy in spontaneously hypertensive rats(SHRs)and to further explore the relationship between autophagy,myocardial remodeling,and injury.The SHRs were randomly assigned to five groups:the model group,the HLJDD low-dose group,the HLJDD medium-dose group,the HLJDD high-dose group,and a positive control group treated with captopril.Additionally,a blank control group was established using Wistar Kyoto(WKY)rats,with 10 rats in each group.The model and blank control groups were administered an equivalent volume of physiological saline via oral gavage,while the treatment groups received their respective doses of HLJDD or captopril by oral gavage.Following the treatments,various parameters were assessed,including blood pressure(systolic,diastolic,and mean arterial pressure),mitochondrial swelling and membrane potential,free ATPase activity,as well as the mRNA and protein levels of autophagy-related factors.The results showed that HLJDD significantly reduced blood pressure(systolic,diastolic,and mean arterial pressure)in SHR rats.Moreover,it enhanced mitochondrial swelling and membrane potential,increased mitochondrial ATPase activity,and decreased the mRNA and protein expression levels of autophagy-related genes(AKT,mTOR,Beclin-1,and LC3-II)in SHRs.The findings of this study suggested that HLJDD could effectively ameliorate myocardial tissue injury in SHRs,and its protective effects on the heart might be attributed to the reduction of autophagy in cardiomyocyte mitochondria.This provided insights into the potential therapeutic use of HLJDD in managing hypertension-induced myocardial injury and remodeling.
基金supported by Fundamental Research Funds for the Central Universities(ZYN2024075)Chengdu Science and Technology Bureau Technology Innovation R&D Project(2024-YF05-02236-SN)the Applied Basic Research Project of the Sichuan Science Technology Department(2021YJ0256).Peer review information。
文摘Background:The traditional Chinese medicine compound Sancao decoction(SCD)is a folk prescription for regulating immunity.It is composed of 8 Chinese herbal medicines,such as Prunellae Spica(Xiakucao),Houttuyniae Herba(Yuxingcao),Lysimachiae Herba(Jinqiancao)and so on.In cancer,the interleukin-6(IL-6)/the signal transducer and the activator of transcription 3(STAT3)pathway directly promotes the proliferation,survival and angiogenesis of cancer cells,and arginase-1(ARG-1)is a key enzyme for myeloid-derived suppressor cells(MDSCs)to exert immunosuppressive function.It is not clear whether SCD regulates the expression of ARG-1 in MDSCs through the IL-6/STAT3 pathway.Therefore,we explored the effect and mechanism of SCD on lung metastasis of breast cancer.Methods:The components in SCD have been analyzed by HPLC-MS.A spontaneous metastasis model of breast cancer was established by injecting 4T1 cells into the mammary fat pad of BALB/c mice.Pre-metastatic niche(PMN)formation and the role of SCD on PMN were evaluated by lung metastasis nodules,lung pathology tests and immunofluorescence for 2–4 weeks.Serum tests and hematoxylin-eosin staining(H&E)were used to evaluate the side effects of cisplatin.Western blot and ELISA were used to detect proteins and cytokines of the STAT3 signaling pathway in mouse lung tissue.Results:Compared with SCD or cisplatin treatment alone,SCD/cisplatin(CP)synergistic administration not only significantly inhibited orthotropic breast tumor growth,but also reduced lung metastasis and alleviated the hepatorenal toxicity induced by CP in vivo.Remarkably,the combination effectively inhibited PMN formation and the accumulation of MDSCs in the lung PMN,accompanied by the significant infiltration of CD4+T and CD8+T-lymphocytes in the lung PMN and spleen.In addition,the SCD/CP combination downregulated protein expression levels of STAT3,p-STAT3,IL-6 and ARG-1 in the lung PMN of breast cancer mice.Conclusion:The synergistic effect of SCD and cisplatin inhibited MDSCs aggregation and the immunosuppressive function of pulmonary PMN,thereby remodeling the immunosuppressive tumor microenvironment and enhancing anti-tumor immunity,leading to remission of orthotopic breast cancer and lung metastases and amelioration of cisplatin-induced liver and kidney toxicity.
基金the"Qin Medicine"Quality Evaluation and Resource Development Discipline Innovation Team Project of Shaanxi University of Traditional Chinese Medicine(2019-QN01)Shaanxi University of Traditional Chinese Medicine School of Pharmacy/Shaanxi Engineering Research Centre for the Application and Development of Qinling Herbal Medicine,"Qin Medicine"Research and Development Key Laboratory(2019-QYPT-002)+2 种基金Shaanxi Provincial Administration of Traditional Chinese Medicine Province,Research and Development Key Laboratory(2019-QYPT-002)Shaanxi Provincial Administration of Traditional Chinese Medicine Province Chinese medicine province-wide earmarked special project:"Qin medicine planting and breeding guide research"(2021-QYZL-02)Shaanxi Provincial Science and Technology Department project:Chinese medicine Scutellaria baicalensis germplasm selection,seedling breeding and planting key technology research(2016KTTSSF01-01-01)and other projects.
文摘Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.
基金support from the Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission(the Specialty Program)(Grant Number:PWZzb2022-21)The Academic Leaders Training Program of Shanghai Pudong New Area Health Commission(Grant Number:PWRd2022-14)+1 种基金The Scientific Research Program of Shanghai Pudong New Area Health Commission(the Achievement Transformation Program)(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.
基金Full-time Introduction of Talent Research Start-up Fund(No.RSC-0015)Key project of Jiangxi Science and Technology Department(No.20203BBE52W010)Jiangxi province Traditional Chinese Medicine science and technology plan project(No.2023B0016,No.2024B0217).
文摘Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of medical treatments in its treatment and the increasing incidence of lung cancer.Traditional Chinese medicine plays an important role in the prevention and treatment of lung cancer.We used network pharmacology to investigate and predict the targets and associated signaling pathways of Wen-Yang-Hua-Liu Decoction(WYHLD)for the treatment of NSCLC.In addition,we investigated the growth mechanism of WYHLD on NSCLC by observing the effects of WYHLD on the processes of NSCLC proliferation,apoptosis,and ferroptosis.Methods:WYHLD drugs were obtained from the TCMSP database and potential targets from the Swiss Target Prediction and Uniprot databases;NSCLC-related genes were collected from the Genecards database;and the intersection genes of WYHLD and NSCLC were obtained from the Venny2.1 platform and imported into the STRING database.The intersection genes of WYHLD and NSCLC were collected from the Genecards database,imported into the STRING database,constructed into a into a protein-protein interaction network(PPI),visualized by Cytoscape 3.9.1 software,and analysed by GO enrichment and KEGG pathway analysis using the Metascape database to predict the direct targets and signaling pathways of WYHLD in the treatment of NSCLC.The NSCLC cell line A549 was cultured,and CCK-8 and wound healing assays were performed to assess cell proliferation and migration.Apoptosis was detected by Hoechst staining.Reactive oxygen species(ROS)levels were measured using flow cytometry.The microstructure of A549 cells observed by transmission electron microscopy.In addition,Western blot was performed to detect MYC,VEGF,HIF-1α,β-catenin,Cleaved-caspase3,GPX4,and SLC7A11 protein expression.Results:The network pharmacological analysis identified 160 WYHLD compounds,1,444 NSCLC disease-related targets,and 133 overlapping WYHLD and NSCLC targets.MYC,AKT1,JUN,ESR1,FOS,TP53,BCL2,and other proteins with high degree values were ranked as therapeutic targets in the STRING 11.0 database.The enriched pathways were identified as being associated with the cancer pathway,the AGE-RAGE signaling pathway,and NSCLC.In in vitro experiments,we found that WYHLD inhibited the migration and proliferation of NSCLC cells and promoted their apoptosis.Analysis of reactive oxygen species showed that WYHLD could promote cellular production of reactive oxygen species.In addition,WYHLD significantly suppressed the expression of MYC,GPX4,SLC7A11,β-catenin,and VEGF while increasing the expression of Cleaved-caspase3.Conclusion:Our results suggest that WYHLD may act as a novel strategy for the prevention and treatment of lung cancer by targeting the Wnt pathway,thereby inhibiting the growth mechanism of NSCLC.
