In this research,a new method based on the hyperspectral imaging for searching the best decocting time of sun dried ginseng is reported.The spectral images at diferent decocting time of test sample have been taken by ...In this research,a new method based on the hyperspectral imaging for searching the best decocting time of sun dried ginseng is reported.The spectral images at diferent decocting time of test sample have been taken by the st aring hyperspectral fAuorescence imaging systen and the solubility of active ingredients have been discussed by analyzing the changes on the spectral.curves.The spectr al range of the system is 400-720nm and the spectral resolution is 5nm.In the decocting process,the active ingredients of nonsoaked ginseng was dissolved in the tissue fluid at first,and reached equilibrium condition at last after the precipitation-dissolution reciprocating process of boiling.At last,the experiment al results show that the best decoction time of sun dried ginseng is about 60 min after boiling.展开更多
Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its wi...Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its widespread use in Japan. In this study, we improved the decocting method by using a microwave oven such as those found in most kitchens. To validate the feasibility and safety of this new method, we decocted kakkonto, which is the most widely used formula in clinical treatment in Japan, and keishikabushito, which contains toxic components using a microwave oven. Regarding the contents of 8 characteristic components in the kakkonto decoction and the contents of 6 toxic components in the keishikabushito decoction as indices, and with the extraction and detoxification effects equal to those of the conventional decocting method as targets, we optimized the decocting conditions with Response Surface Methods. With this new method, it took 35 min to obtain almost the same extraction effect for kakkonto as with the conventional decocting method, which takes 40 min;meanwhile, it took only 45 min to detoxify keishikabushito, which takes 60 min using the conventional decocting method. Decocting Kampo medicines with a microwave oven is feasible and as safe as the conventional decocting method. It is a convenient, safe, time-saving method, and may be applied widely in clinical practice. This innovation should allow more patients to benefit from decoction and the individualized treatment it offers.展开更多
Astragalus is an important traditional Chinese herb that has therapeutic potential in the treatment of diseases. In this study, the dissolution of metallic elements during the material decoction process was investigat...Astragalus is an important traditional Chinese herb that has therapeutic potential in the treatment of diseases. In this study, the dissolution of metallic elements during the material decoction process was investigated using laser-induced breakdown spectroscopy(LIBS). The Ca, Mg, Al, and Fe in the drug residues, liquid, and vapor were selected for the study of the transfer of elements after different decocting times. It was found that the intensities of the spectral lines for these elements in the drug liquid increased with increasing decocting times.The contrast trend was observed in the residues and only calcium was detected in the vapor.Furthermore, the relative mass concentrations of Ca, Mg, Al, and Fe in the liquid were quantitatively determined by a combination of the standard addition method and calibrationfree-LIBS method by adding the standard concentration solution of Cu and Cd elements into the drug liquids, it can be found that the maximum error between Cd concentration calculated by internal CF-LIBS and the standard is within 10%. This provides a new method of achieving the on-line monitoring and analysis of metallic elements in the production of traditional Chinese medicines.展开更多
OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was establi...OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was established and therapeutic effects of GQD were determined by detecting body weight,disease activity index(DAI),colon length and histopathological changes.Then,the expression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay,the expression levels of tight junction proteins were detected by immunohistochemistry and the expression levels of ferroptosis-associated proteins were detected by western blotting.RESULTS:GQD treatment attenuated weight loss and DAI score,increased colon length,ameliorated intestinal histopathological damage,inhibited colonic inflammatory cytokine release and enhanced epithelial barrier function in mice with ulcerative colitis(UC).Furthermore,GQD administration obviously improved the expression of ferroptosis-associated proteins(solute carrier family 7 member 11 and acyl-Co A synthetase long chain family member 4).CONCLUSION:GQD could exert a therapeutic effect on colitis by alleviating colon damage and promoting intestinal mucosal barrier repair in DSS-induced colitis mice through the inhibition of ferroptosis,which may provide an effective natural therapy for the treatment of UC.展开更多
OBJECTIVE:To investigate the key targets and mechanisms of the Wenyang Huayin decoction(WYHYD,温阳化饮方)in treating bronchial asthma with cold fluid retention syndrome using network pharmacology and animal experiment...OBJECTIVE:To investigate the key targets and mechanisms of the Wenyang Huayin decoction(WYHYD,温阳化饮方)in treating bronchial asthma with cold fluid retention syndrome using network pharmacology and animal experiments.METHODS:On the one hand,we used network pharmacology method to explored the chemical components of the WYHYD and the main targets of bronchial asthma were acquired.Besides,a protein interaction network was built after protein interaction analysis to find potential protein functional modules.Then,we constructed the"WYHYD component-bronchial asthma target-pathway"network.On the other hand,the experimental intervention was as follows:first,we formed a rat model of bronchial asthma.Thereafter,we used the WYHYD to treat the disease while observing autophagyrelated indicators as the core target of network pharmacology.RESULTS:The network pharmacology revealed that there are 122 potential therapeutic targets in treating bronchial asthma with WYHYD.The biological processes mainly involved in the WYHYD included Gene Ontology:0110032:positive regulation of G2/MI transition of the medical cell cycle etc.and four major signaling pathways were involved.During laboratory investigations,various signs and clinical manifestations of the rat model group were the same.After administering the WYHYD,lung function,pathological sections,inflammatory factors,and other microscopic indicators improved to varying degrees,providing evidence for the study results.Meanwhile,we verified that the core targets of WYHYD in treating asthma through the intervention of autophagy are tumor necrosis factor,caspase 8,interleukin 1 beta,sirtuin 1,phosphatidylinositol 3-kinase catalytic subunit type 3,C-C chemokine receptor type 7,L/YN kinase,and protein tyrosine kinase 2.CONCLUSION:This preliminary study revealed the treatment process of bronchial asthma with multicomponent,multi-target,and multi-pathway mechanisms of the WYHYD.展开更多
Background:Parkinson’s disease(PD)is one of the most common movement disorders worldwide.Ziyin Xifeng Decoction(ZYXFD),a traditional Chinese medicine compound formula,has shown therapeutic efficacy in treating PD,but...Background:Parkinson’s disease(PD)is one of the most common movement disorders worldwide.Ziyin Xifeng Decoction(ZYXFD),a traditional Chinese medicine compound formula,has shown therapeutic efficacy in treating PD,but its specific mechanisms of action have not been fully elucidated.Methods:Firstly,we employed network pharmacology and untargeted metabolomics analysis to identify the core targets,pathways,and key metabolites of ZYXFD in the treatment of PD.Subsequently,we evaluated the protective effects of ZYXFD and further investigated its anti-PD mechanisms by validating the analytical results.Results:Combined analyses of network pharmacology and metabolomics identify the core targets including EGFR,SRC,PTGS2,and CDK2,while the effects of ZYXFD against PD are likely mediated primarily through the PI3K/AKT/mTOR signaling pathway.Pharmacodynamic evaluation demonstrated that a high dose of ZYXFD significantly improved behavioral deficits in chronic PD mice,downregulatedα-synuclein protein expression,and protected dopaminergic neurons.It also regulated the expression of core targets,inhibited the PI3K/AKT/mTOR signaling pathway,promoted autophagy,and reduced apoptosis.In vitro experiments further verified that the therapeutic effect of ZYXFD on PD is dependent on autophagy regulation.Conclusion:The findings demonstrated that ZYXFD alleviates PD by modulating related proteins and metabolites,inhibiting the PI3K/AKT/mTOR signaling pathway,and enhancing autophagy.This provides a theoretical basis for its broader application in PD treatment.展开更多
Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathwa...Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathways in mice, and providing a scientific basis for clinical treatment. Methods: An acute colitis model in mice was established by administering dextran sodium sulfate (DSS) in drinking water continuously for 7 days. After successful modeling, the mice were randomly divided into an ulcerative colitis model group, a mesalazine group, and low-, medium-, and high-dose Dahuang Mudan Decoction groups. The intervention was administered via continuous gavage for 7 days. Body weight changes and colon length were recorded, and the disease activity index (DAI) and fecal occult blood status were monitored. Colon length was measured, and colon tissue was subjected to HE staining and pathological scoring to assess inflammatory damage. Intestinal tissue samples were collected for metabolomic analysis to screen for differential metabolites and perform pathway enrichment analysis. Results: The experimental results indicated that, compared with the model group, intervention with Dahuang Mudan Decoction significantly improved the colitis phenotype induced by DSS, as evidenced by alleviated weight loss, reduced DAI scores, decreased colon shortening, and mitigated histopathological damage, along with improved inflammatory cell infiltration and crypt structure destruction. Metabolomic analysis revealed a clear separation in metabolic profiles between the model and normal groups. Conclusion: Dahuang Mudan Decoction induced a holistic shift in the metabolic phenotype of the model mice, partially reverting/remodeling it toward the normal state.展开更多
This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly,...This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly, the effective activecomponents of the Chinese herbs in HGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and their potential therapeutic targets were predicted using the Swiss Target Prediction platform. Subsequently, PErelatedtarget genes were obtained from the Online Mendelian Inheritance in Man (OMIM) database and GeneCards database.Then, the Wei Sheng Xin tool was used to generate a Venn diagram for identifying the common targets between the herb-relatedtargets and PE-related targets. After screening these common targets, a “drug-component-target network” and a protein-proteininteraction (PPI) network were constructed. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia ofGenes and Genomes (KEGG) enrichment analysis were conducted on the intersecting targets, and molecular docking verificationwas performed using AutoDockTools and PyMol software. Finally, 20 active components were screened from Astragali Radix, 7from Cinnamomi Ramulus, 13 from Paeoniae Radix Alba, 5 from Zingiberis Rhizoma Recens, and 29 from Jujubae Fructus, witha total of 983 therapeutic targets. Among these targets, 134 were associated with PE, and protein kinase B1 (AKT1), mitogenactivatedprotein kinase 1 (MAPK1), and transformation-related protein 53 (TP53) served as the core targets. The results of GOand KEGG enrichment analyses indicated that the alleviation of PE by HGD is mainly related to pathways including immuneresponse, regulation of gene expression, atherosclerosis, and tumorigenesis. Molecular docking results showed that the keyactive components in HGD could bind to the core targets spontaneously and stably. This study revealed that HGD may alleviatesymptoms in PE patients by regulating signaling pathways, modulating platelet function to exert anticoagulant effects, andregulating the expression of anti-inflammatory genes, which provided a direction for subsequent experimental research.展开更多
Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex me...Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B(NF-κB), phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(AKT), Toll-like receptor 4(TLR4), mitogen-activated protein kinase(MAPK), and mammalian target of rapamycin(mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine(TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.展开更多
Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J ...Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J mice were randomly assigned to a control group(n=6)and a 4-nitroquinoline 1-oxide(4-NQO)-exposed group(n=24).Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water(100μg/mL)for 17 consecutive weeks,whereas control group received sterile drinking water.After model establishment,the mice in 4-NQOexposed group were further randomized into model group and three BXXXD-treated groups:low-dose(BXXXD-L,3.7 g/kg),medium-dose(BXXXD-M,7.4 g/kg),and high-dose(BXXXDH,14.8 g/kg)groups(n=6 per group).During the subsequent intervention period,mice in control and model groups were gavaged with sterile water,while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks.Histopathological changes in esophageal tissues were observed by hematoxylin and eosin(HE)staining.The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity,community structure,and co-occurrence networks.BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry(UHPLCQE-MS).Serum short-chain fatty acids(SCFA)level was quantified by targeted metabolomics using gas chromatography-mass spectrometry(GC-MS).Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles.Results Compared with model group,BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement,with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups(P<0.01).Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus.In the gut,BXXXD elevated the relative abundance of beneficial taxa,including Lactobacillus,Dubosiella,Bacteroides,and Faecalibacterium.Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level(P<0.01).Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression,migration,and invasion of esophageal cancer,which were identified as kallikrein-related peptidase 6(Klk6),defensin beta 4(Defb4),family with sequence similarity 3 member B(Fam3b),carboxypeptidase A4(Cpa4),serum amyloid A1(Saa1),and chitinase-like 1(Chil1)(P<0.05).Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.展开更多
OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with e...OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.展开更多
Ganmai Dazao Decoction,originating from“Jin Gui Yao Lue”(Synopsis of the Golden Chamber),is a classical prescription for treating visceral agitation.Composed of three medicinal and edible substances-licorice(Gancao)...Ganmai Dazao Decoction,originating from“Jin Gui Yao Lue”(Synopsis of the Golden Chamber),is a classical prescription for treating visceral agitation.Composed of three medicinal and edible substances-licorice(Gancao),wheat(Xiaomai),and jujube(Dazao),it functions to nourish the heart and calm the mind,harmonize the middle burner and regulate Qi,and alleviate urgency and restlessness.As its clinical application has expanded from traditional emotional disorders to neurological,endocrine,and various psychosomatic diseases,establishing a scientifically precise quality control system and deeply elucidating its pharmacodynamic material basis and mechanism of action have become critical tasks.Modern analytical methods,typified by chromatography,spectroscopy,and their hyphenated techniques,with their high sensitivity,high resolution,and powerful substance characterization capabilities,have become the core driving force for standardizing the quality control and modernizing the clinical application research of this formula.This paper systematically reviews the progress of the aforementioned analytical techniques and chemometrics in interpreting the chemical composition,establishing fingerprint profiles,controlling process quality,and researching the pharmacodynamic material basis of Ganmai Dazao Decoction.Furthermore,it discusses integrated approaches combining analytical techniques with pharmacology and clinical medicine to reveal mechanisms of action and explore therapeutic biomarkers.Finally,it provides an outlook on future directions and challenges,including technological integration and innovation,standardization of whole-process quality control systems,and evidence-based research aimed at internationalization.展开更多
BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
OBJECTIVE:To investigate the effects of optimizing Qinggan Jieyu decoction(清肝解郁方)on purinergic receptor P2X ligand-gated ion channel 7(P2X7R)and autophagy in migraine model rats based on molecular biology and his...OBJECTIVE:To investigate the effects of optimizing Qinggan Jieyu decoction(清肝解郁方)on purinergic receptor P2X ligand-gated ion channel 7(P2X7R)and autophagy in migraine model rats based on molecular biology and histopathology.METHODS:A migraine rat model was established by a single subcutaneous nitroglycerin(NTG)injection into the posterior neck.QGJY was administered via gavage for 7 d prior to NTG induction.Behavioral changes,central sensitization biomarkers,and inflammatory cytokine levels were analyzed to evaluate migraine severity.Western blot,immunofluorescence,quantitative real-time PCR,and transmission electron microscopy were employed to assess P2X7R expression and autophagy activity in trigeminal nucleus caudalis(TNC)tissues.The P2X7R agonist 2'(3')-O-(4-Benzoylbenzoyl)adenosine-5'-triphosphate(Bz ATP)was further utilized to validate QGJY's regulatory effects.RESULTS:QGJY significantly reduced cage-climbing and head-scratching frequencies in NTG-induced migraine rats,downregulated serum and TNC levels of interleukin-1 beta,interleukin-6,and tumor necrosis factor-alpha,and suppressed central sensitization markers(substance P;calcitonin gene-related peptide;and c-fos induced growth factor)in TNC tissues(P<0.05).QGJY markedly decreased microglial cell counts and average immunofluorescence intensity in TNC tissues and promoted elongation of microglial protrusions(P<0.05).Concurrently,QGJY downregulated P2X7R protein and m RNA expression,reduced the light chain 3(LC3)-II/LC3-I ratio,elevated ubiquitin-binding protein p62 levels,and diminished autophagosome numbers in TNC tissues(P<0.05).Furthermore,QGJY reversed Bz ATP-induced P2X7R upregulation(P<0.05).CONCLUSIONS:QGJY alleviates migraine and inhibits central sensitization in rats,potentially by downregulating P2X7R expression,concomitantly suppressing autophagy,attenuating microglial activation,and reducing pro-inflammatory cytokine release.展开更多
[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]T...[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.展开更多
Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in m...Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.展开更多
OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted...OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
OBJECTIVE:To investigate the mechanism of action of Qinlian Jiangxia decoction(芩连姜夏汤,QLJXD)in the treatment of type 2 diabetes mellitus(T2DM)complicated by hyperlipidemia using network pharmacology,molecular dock...OBJECTIVE:To investigate the mechanism of action of Qinlian Jiangxia decoction(芩连姜夏汤,QLJXD)in the treatment of type 2 diabetes mellitus(T2DM)complicated by hyperlipidemia using network pharmacology,molecular docking,molecular dynamics simulation and in vivo experiments.METHODS:Drug components,targets and disease targets were identified using databases such as TCM systems pharmacology database and analysis platform and Gene Cards.The intersecting targets were subjected to protein-protein interaction analysis using the search tool for the retrieval of interacting genes/proteins database.Subsequently,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the intersecting targets were conducted using the Metascape platform to identify core components and targets.The results were validated using molecular docking,molecular dynamics simulations and in vivo experiments.RESULTS:QLJXD contains 76 active ingredients and 136 disease targets.The core ingredients are quercetin,β-sitosterol,wogonin and baicalein,while the core targets are fatty acid binding protein 4(FABP4)and peroxisome proliferative activated receptor gamma(PPARG).Molecular docking and molecular dynamics simulations revealed that the core ingredients bound well to the core targets.Animal experiments demonstrated that QLJXD effectively inhibited the expression of FABP4 and increased the expression of PPARG,thereby enhancing disorders of glycolipid metabolism.CONCLUSION:The putative therapeutic efficacy of QLJXD in the management of T2DM complicated with hyperlipidemia may be ascribed to the synergistic actions of multiple components,such as quercetin,β-sitosterol,wogonin,and baicalein,which collectively modulate FABP4 and PPARG molecular targets.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
文摘In this research,a new method based on the hyperspectral imaging for searching the best decocting time of sun dried ginseng is reported.The spectral images at diferent decocting time of test sample have been taken by the st aring hyperspectral fAuorescence imaging systen and the solubility of active ingredients have been discussed by analyzing the changes on the spectral.curves.The spectr al range of the system is 400-720nm and the spectral resolution is 5nm.In the decocting process,the active ingredients of nonsoaked ginseng was dissolved in the tissue fluid at first,and reached equilibrium condition at last after the precipitation-dissolution reciprocating process of boiling.At last,the experiment al results show that the best decoction time of sun dried ginseng is about 60 min after boiling.
文摘Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its widespread use in Japan. In this study, we improved the decocting method by using a microwave oven such as those found in most kitchens. To validate the feasibility and safety of this new method, we decocted kakkonto, which is the most widely used formula in clinical treatment in Japan, and keishikabushito, which contains toxic components using a microwave oven. Regarding the contents of 8 characteristic components in the kakkonto decoction and the contents of 6 toxic components in the keishikabushito decoction as indices, and with the extraction and detoxification effects equal to those of the conventional decocting method as targets, we optimized the decocting conditions with Response Surface Methods. With this new method, it took 35 min to obtain almost the same extraction effect for kakkonto as with the conventional decocting method, which takes 40 min;meanwhile, it took only 45 min to detoxify keishikabushito, which takes 60 min using the conventional decocting method. Decocting Kampo medicines with a microwave oven is feasible and as safe as the conventional decocting method. It is a convenient, safe, time-saving method, and may be applied widely in clinical practice. This innovation should allow more patients to benefit from decoction and the individualized treatment it offers.
基金This work was supported by National Natural Science Foundation of China(Nos.61965015,11564037,61741513,11364037)The Special Fund Project for Guiding Scientific and Technological Innovation of Gansu Province(No.2019zx-10)Young Teachers Scientific Research Ability Promotion Plan of Northwest Normal University(No.NWNU-LKQN2019-1).
文摘Astragalus is an important traditional Chinese herb that has therapeutic potential in the treatment of diseases. In this study, the dissolution of metallic elements during the material decoction process was investigated using laser-induced breakdown spectroscopy(LIBS). The Ca, Mg, Al, and Fe in the drug residues, liquid, and vapor were selected for the study of the transfer of elements after different decocting times. It was found that the intensities of the spectral lines for these elements in the drug liquid increased with increasing decocting times.The contrast trend was observed in the residues and only calcium was detected in the vapor.Furthermore, the relative mass concentrations of Ca, Mg, Al, and Fe in the liquid were quantitatively determined by a combination of the standard addition method and calibrationfree-LIBS method by adding the standard concentration solution of Cu and Cd elements into the drug liquids, it can be found that the maximum error between Cd concentration calculated by internal CF-LIBS and the standard is within 10%. This provides a new method of achieving the on-line monitoring and analysis of metallic elements in the production of traditional Chinese medicines.
基金National Natural Science Foundation Project:Study on the Mechanism of Gegen Qinlian Decoction in Reshaping Macrophage Polarization via Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2-Mediated Neutrophil Extracellular Traps Formation for the Treatment of Ulcerative Colitis with Dampness-Heat Syndrome(No.82505455)。
文摘OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was established and therapeutic effects of GQD were determined by detecting body weight,disease activity index(DAI),colon length and histopathological changes.Then,the expression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay,the expression levels of tight junction proteins were detected by immunohistochemistry and the expression levels of ferroptosis-associated proteins were detected by western blotting.RESULTS:GQD treatment attenuated weight loss and DAI score,increased colon length,ameliorated intestinal histopathological damage,inhibited colonic inflammatory cytokine release and enhanced epithelial barrier function in mice with ulcerative colitis(UC).Furthermore,GQD administration obviously improved the expression of ferroptosis-associated proteins(solute carrier family 7 member 11 and acyl-Co A synthetase long chain family member 4).CONCLUSION:GQD could exert a therapeutic effect on colitis by alleviating colon damage and promoting intestinal mucosal barrier repair in DSS-induced colitis mice through the inhibition of ferroptosis,which may provide an effective natural therapy for the treatment of UC.
基金Supported by National Natural Science Foundation of China:Study on the Mechanism of Airway Inflammation in Rats with Bronchial Asthma Cold Drink Lung Syndrome Treated with Metastasis Associated Lung Adenocarcinoma Transcript 1 Regulated Autophagy(No.82004233)the Shandong Province Traditional Chinese Medicine Science and Technology Project:Exploring the Mechanism of Xiaoqinglong Tang's Intervention in Bronchial Asthma Cold Drink Lung Syndrome through the"Temperature Sensing Channel Transient Receptor Potential Mitochondrial Autophagy"Pathway based on Transcriptomics Combined with Proteomics(No.MR20241737)+3 种基金Shandong Province Traditional Chinese Medicine Science and Technology Project:Optimization of Ultrasonic Extraction Process and Study on Structure and Activity of Asarum Polysaccharides(No.Q-2023042)Shandong Province Traditional Chinese Medicine Science and Technology Project:Study on the Mechanism of Ma Gui Synergistic Intervention on Airway Inflammatory Response in Rats with Asthma Cold Drink and Lung Accumulation Syndrome(No.Q-2023122)2023 Qilu Biancang Traditional Chinese Medicine Talent Cultivation ProjectShandong Province Medical and Health Science and Technology Development Plan Project:Study on the Mechanism of Airway Epithelial Cell Inflammation Induced by Cellular Autophagy Regulation lnc RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 Antagonism Against Ovalbumin Intervention(No.202203020866)。
文摘OBJECTIVE:To investigate the key targets and mechanisms of the Wenyang Huayin decoction(WYHYD,温阳化饮方)in treating bronchial asthma with cold fluid retention syndrome using network pharmacology and animal experiments.METHODS:On the one hand,we used network pharmacology method to explored the chemical components of the WYHYD and the main targets of bronchial asthma were acquired.Besides,a protein interaction network was built after protein interaction analysis to find potential protein functional modules.Then,we constructed the"WYHYD component-bronchial asthma target-pathway"network.On the other hand,the experimental intervention was as follows:first,we formed a rat model of bronchial asthma.Thereafter,we used the WYHYD to treat the disease while observing autophagyrelated indicators as the core target of network pharmacology.RESULTS:The network pharmacology revealed that there are 122 potential therapeutic targets in treating bronchial asthma with WYHYD.The biological processes mainly involved in the WYHYD included Gene Ontology:0110032:positive regulation of G2/MI transition of the medical cell cycle etc.and four major signaling pathways were involved.During laboratory investigations,various signs and clinical manifestations of the rat model group were the same.After administering the WYHYD,lung function,pathological sections,inflammatory factors,and other microscopic indicators improved to varying degrees,providing evidence for the study results.Meanwhile,we verified that the core targets of WYHYD in treating asthma through the intervention of autophagy are tumor necrosis factor,caspase 8,interleukin 1 beta,sirtuin 1,phosphatidylinositol 3-kinase catalytic subunit type 3,C-C chemokine receptor type 7,L/YN kinase,and protein tyrosine kinase 2.CONCLUSION:This preliminary study revealed the treatment process of bronchial asthma with multicomponent,multi-target,and multi-pathway mechanisms of the WYHYD.
基金funded by Zhejiang Province Traditional Chinese Medicine Science and Technology Program(No.2021ZZ012)The Changlin Qiu National Distinguished Senior Traditional Chinese Medicine Expert Heritage Workshop Project(No.GZS2021007).
文摘Background:Parkinson’s disease(PD)is one of the most common movement disorders worldwide.Ziyin Xifeng Decoction(ZYXFD),a traditional Chinese medicine compound formula,has shown therapeutic efficacy in treating PD,but its specific mechanisms of action have not been fully elucidated.Methods:Firstly,we employed network pharmacology and untargeted metabolomics analysis to identify the core targets,pathways,and key metabolites of ZYXFD in the treatment of PD.Subsequently,we evaluated the protective effects of ZYXFD and further investigated its anti-PD mechanisms by validating the analytical results.Results:Combined analyses of network pharmacology and metabolomics identify the core targets including EGFR,SRC,PTGS2,and CDK2,while the effects of ZYXFD against PD are likely mediated primarily through the PI3K/AKT/mTOR signaling pathway.Pharmacodynamic evaluation demonstrated that a high dose of ZYXFD significantly improved behavioral deficits in chronic PD mice,downregulatedα-synuclein protein expression,and protected dopaminergic neurons.It also regulated the expression of core targets,inhibited the PI3K/AKT/mTOR signaling pathway,promoted autophagy,and reduced apoptosis.In vitro experiments further verified that the therapeutic effect of ZYXFD on PD is dependent on autophagy regulation.Conclusion:The findings demonstrated that ZYXFD alleviates PD by modulating related proteins and metabolites,inhibiting the PI3K/AKT/mTOR signaling pathway,and enhancing autophagy.This provides a theoretical basis for its broader application in PD treatment.
文摘Objective: This study aims to systematically explore the mechanism of Dahuang Mudan Decoction in treating inflammatory bowel disease through metabolomic analysis, revealing its therapeutic effects and potential pathways in mice, and providing a scientific basis for clinical treatment. Methods: An acute colitis model in mice was established by administering dextran sodium sulfate (DSS) in drinking water continuously for 7 days. After successful modeling, the mice were randomly divided into an ulcerative colitis model group, a mesalazine group, and low-, medium-, and high-dose Dahuang Mudan Decoction groups. The intervention was administered via continuous gavage for 7 days. Body weight changes and colon length were recorded, and the disease activity index (DAI) and fecal occult blood status were monitored. Colon length was measured, and colon tissue was subjected to HE staining and pathological scoring to assess inflammatory damage. Intestinal tissue samples were collected for metabolomic analysis to screen for differential metabolites and perform pathway enrichment analysis. Results: The experimental results indicated that, compared with the model group, intervention with Dahuang Mudan Decoction significantly improved the colitis phenotype induced by DSS, as evidenced by alleviated weight loss, reduced DAI scores, decreased colon shortening, and mitigated histopathological damage, along with improved inflammatory cell infiltration and crypt structure destruction. Metabolomic analysis revealed a clear separation in metabolic profiles between the model and normal groups. Conclusion: Dahuang Mudan Decoction induced a holistic shift in the metabolic phenotype of the model mice, partially reverting/remodeling it toward the normal state.
基金supported by Research Project on Traditional Chinese Medicine in Heilongjiang Province in 2025(Research on the pharmacological substance basis of Huangqi Guizhi decoction in improving acute pulmonary embolism and lung injury based on the theory of“Diaphoresis and expanding meridian”No.ZHY2025-043).
文摘This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly, the effective activecomponents of the Chinese herbs in HGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and their potential therapeutic targets were predicted using the Swiss Target Prediction platform. Subsequently, PErelatedtarget genes were obtained from the Online Mendelian Inheritance in Man (OMIM) database and GeneCards database.Then, the Wei Sheng Xin tool was used to generate a Venn diagram for identifying the common targets between the herb-relatedtargets and PE-related targets. After screening these common targets, a “drug-component-target network” and a protein-proteininteraction (PPI) network were constructed. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia ofGenes and Genomes (KEGG) enrichment analysis were conducted on the intersecting targets, and molecular docking verificationwas performed using AutoDockTools and PyMol software. Finally, 20 active components were screened from Astragali Radix, 7from Cinnamomi Ramulus, 13 from Paeoniae Radix Alba, 5 from Zingiberis Rhizoma Recens, and 29 from Jujubae Fructus, witha total of 983 therapeutic targets. Among these targets, 134 were associated with PE, and protein kinase B1 (AKT1), mitogenactivatedprotein kinase 1 (MAPK1), and transformation-related protein 53 (TP53) served as the core targets. The results of GOand KEGG enrichment analyses indicated that the alleviation of PE by HGD is mainly related to pathways including immuneresponse, regulation of gene expression, atherosclerosis, and tumorigenesis. Molecular docking results showed that the keyactive components in HGD could bind to the core targets spontaneously and stably. This study revealed that HGD may alleviatesymptoms in PE patients by regulating signaling pathways, modulating platelet function to exert anticoagulant effects, andregulating the expression of anti-inflammatory genes, which provided a direction for subsequent experimental research.
基金supported by the National Natural Science Foundation of China (Nos. 82104430 and 82274133)the Shanghai Sailing Program (No. 21YF1447600)the Future Plan for Traditional Chinese Medicine Development of Science and Technology of Shanghai Municipal Hospital of Traditional Chinese Medicine (No. WL-HBQN-2022002K)。
文摘Taohong Siwu Decoction(THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis(AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B(NF-κB), phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(AKT), Toll-like receptor 4(TLR4), mitogen-activated protein kinase(MAPK), and mammalian target of rapamycin(mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine(TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.
基金National Natural Science Foundation of China(82274369).
文摘Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions.Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J mice were randomly assigned to a control group(n=6)and a 4-nitroquinoline 1-oxide(4-NQO)-exposed group(n=24).Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water(100μg/mL)for 17 consecutive weeks,whereas control group received sterile drinking water.After model establishment,the mice in 4-NQOexposed group were further randomized into model group and three BXXXD-treated groups:low-dose(BXXXD-L,3.7 g/kg),medium-dose(BXXXD-M,7.4 g/kg),and high-dose(BXXXDH,14.8 g/kg)groups(n=6 per group).During the subsequent intervention period,mice in control and model groups were gavaged with sterile water,while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks.Histopathological changes in esophageal tissues were observed by hematoxylin and eosin(HE)staining.The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity,community structure,and co-occurrence networks.BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry(UHPLCQE-MS).Serum short-chain fatty acids(SCFA)level was quantified by targeted metabolomics using gas chromatography-mass spectrometry(GC-MS).Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles.Results Compared with model group,BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement,with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups(P<0.01).Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus.In the gut,BXXXD elevated the relative abundance of beneficial taxa,including Lactobacillus,Dubosiella,Bacteroides,and Faecalibacterium.Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level(P<0.01).Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression,migration,and invasion of esophageal cancer,which were identified as kallikrein-related peptidase 6(Klk6),defensin beta 4(Defb4),family with sequence similarity 3 member B(Fam3b),carboxypeptidase A4(Cpa4),serum amyloid A1(Saa1),and chitinase-like 1(Chil1)(P<0.05).Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.
基金Supported by Shandong Provincial Natural Science,Study on the Structure-Activity Relationship and Mechanism of Licorice Chalcone Components in Synergizing with Immune Checkpoint Inhibitors for Anticancer Therapy(No.ZR2020MH380)Mechanisms of the Novel Flavone C-Glycoside 6'-ORhamnosyllutonarin from Dianthus superbus Improves Non-alcoholic Fatty Liver Disease via Modulating the Juxtaposed with Another Zinc Finger gene 1/Adenosine Monophosphate-activated Protein Kinase/Sterol Regulatory Element-Binding Protein Pathway(No.ZR2024MC209)。
文摘OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.
文摘Ganmai Dazao Decoction,originating from“Jin Gui Yao Lue”(Synopsis of the Golden Chamber),is a classical prescription for treating visceral agitation.Composed of three medicinal and edible substances-licorice(Gancao),wheat(Xiaomai),and jujube(Dazao),it functions to nourish the heart and calm the mind,harmonize the middle burner and regulate Qi,and alleviate urgency and restlessness.As its clinical application has expanded from traditional emotional disorders to neurological,endocrine,and various psychosomatic diseases,establishing a scientifically precise quality control system and deeply elucidating its pharmacodynamic material basis and mechanism of action have become critical tasks.Modern analytical methods,typified by chromatography,spectroscopy,and their hyphenated techniques,with their high sensitivity,high resolution,and powerful substance characterization capabilities,have become the core driving force for standardizing the quality control and modernizing the clinical application research of this formula.This paper systematically reviews the progress of the aforementioned analytical techniques and chemometrics in interpreting the chemical composition,establishing fingerprint profiles,controlling process quality,and researching the pharmacodynamic material basis of Ganmai Dazao Decoction.Furthermore,it discusses integrated approaches combining analytical techniques with pharmacology and clinical medicine to reveal mechanisms of action and explore therapeutic biomarkers.Finally,it provides an outlook on future directions and challenges,including technological integration and innovation,standardization of whole-process quality control systems,and evidence-based research aimed at internationalization.
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
基金Supported by the China Academy of Chinese Medical Sciences Innovation Fund:Multicenter Randomized Controlled Study on the Intervention of Yiqi Huoxue Huatan Tongluo decoction in Post-Stent Restenosis of Vertebral Arteries(No.CI2021A01308)In-Hospital Mentorship Program of Xiyuan Hospital,China Academy of Chinese Medical Sciences-Zhou Shaohua(No.0203055)。
文摘OBJECTIVE:To investigate the effects of optimizing Qinggan Jieyu decoction(清肝解郁方)on purinergic receptor P2X ligand-gated ion channel 7(P2X7R)and autophagy in migraine model rats based on molecular biology and histopathology.METHODS:A migraine rat model was established by a single subcutaneous nitroglycerin(NTG)injection into the posterior neck.QGJY was administered via gavage for 7 d prior to NTG induction.Behavioral changes,central sensitization biomarkers,and inflammatory cytokine levels were analyzed to evaluate migraine severity.Western blot,immunofluorescence,quantitative real-time PCR,and transmission electron microscopy were employed to assess P2X7R expression and autophagy activity in trigeminal nucleus caudalis(TNC)tissues.The P2X7R agonist 2'(3')-O-(4-Benzoylbenzoyl)adenosine-5'-triphosphate(Bz ATP)was further utilized to validate QGJY's regulatory effects.RESULTS:QGJY significantly reduced cage-climbing and head-scratching frequencies in NTG-induced migraine rats,downregulated serum and TNC levels of interleukin-1 beta,interleukin-6,and tumor necrosis factor-alpha,and suppressed central sensitization markers(substance P;calcitonin gene-related peptide;and c-fos induced growth factor)in TNC tissues(P<0.05).QGJY markedly decreased microglial cell counts and average immunofluorescence intensity in TNC tissues and promoted elongation of microglial protrusions(P<0.05).Concurrently,QGJY downregulated P2X7R protein and m RNA expression,reduced the light chain 3(LC3)-II/LC3-I ratio,elevated ubiquitin-binding protein p62 levels,and diminished autophagosome numbers in TNC tissues(P<0.05).Furthermore,QGJY reversed Bz ATP-induced P2X7R upregulation(P<0.05).CONCLUSIONS:QGJY alleviates migraine and inhibits central sensitization in rats,potentially by downregulating P2X7R expression,concomitantly suppressing autophagy,attenuating microglial activation,and reducing pro-inflammatory cytokine release.
基金Supported by National Natural Science Foundation of China(82160832)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNS-FAA198255)+2 种基金Open Project of Guangxi Key Laboratory of Brain and Cognitive Neuroscience(GKLBCN-202206-02)Guangxi Undergraduate Innovation and Entrepreneurship Training Program(202410601029,S202410601113)The 4th Thousand Young and Middle-Aged Backbone Teachers Cultivation Program of Guangxi Higher Education Institutions.
文摘[Objectives]To investigate the ameliorative effects of Huanglian Jiedu Decoction(HLJDD)on cognitive function impairment in an Alzheimer s disease(AD)mouse model induced by Porphyromonas gingivalis infection.[Methods]Thirty-six male C57BL/6 mice were randomly assigned to six groups:control group,model group,low-dose HLJDD group,medium-dose HLJDD group,high-dose HLJDD group,and positive drug group(treated with moxifloxacin).With the exception of the control group,all groups underwent an 8-week P.gingivalis chronic infection model induced via oral administration.Subsequently,each treatment group received corresponding doses of HLJDD(2.5,5,and 10 mg/g)or moxifloxacin for 8 weeks intervention.The novel object recognition test was employed to evaluate the non-spatial memory abilities of mice,and the novel object exploration preference index was calculated to assess cognitive function.[Results]Compared to the control group,the novel object exploration preference index of mice in the model group was significantly reduced(P<0.01),indicating that P.gingivalis infection effectively induced cognitive impairment.Relative to the model group,mice treated with medium and high doses of HLJDD exhibited a significant,dose-dependent increase in the novel object exploration preference index,whereas the low-dose group showed no significant improvement.Additionally,the positive drug moxifloxacin demonstrated a significant neuroprotective effect on cognition.[Conclusions]HLJDD effectively improves cognitive function impairment in AD model mice induced by P.gingivalis infection,offering novel experimental evidence supporting the heat-clearing and detoxification approach as well as the therapeutic potential of traditional Chinese medicine(TCM)compounds in the intervention of AD.
基金supported by the National Science Foundation of China(No.82405004,82474253)the Natural Science Foundation postdoctoral project of Chongqing(CSTB2022NSCQ-BHX0709)+2 种基金Chongqing Wanzhou District doctoral“through train”scientific research project(wzstc-20220124)Natural Science Foundation of Chongqing,China(No.Cstc2021jcyj-msxmX0996)Chongqing Wanzhou District Science and Health Joint Medical Research Project(wzstc-kw2023032)。
文摘Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.
基金Supported by the Nanjing Health Science and Technology Key Medical Science and Technology Development Program:Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)。
文摘OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
文摘OBJECTIVE:To investigate the mechanism of action of Qinlian Jiangxia decoction(芩连姜夏汤,QLJXD)in the treatment of type 2 diabetes mellitus(T2DM)complicated by hyperlipidemia using network pharmacology,molecular docking,molecular dynamics simulation and in vivo experiments.METHODS:Drug components,targets and disease targets were identified using databases such as TCM systems pharmacology database and analysis platform and Gene Cards.The intersecting targets were subjected to protein-protein interaction analysis using the search tool for the retrieval of interacting genes/proteins database.Subsequently,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the intersecting targets were conducted using the Metascape platform to identify core components and targets.The results were validated using molecular docking,molecular dynamics simulations and in vivo experiments.RESULTS:QLJXD contains 76 active ingredients and 136 disease targets.The core ingredients are quercetin,β-sitosterol,wogonin and baicalein,while the core targets are fatty acid binding protein 4(FABP4)and peroxisome proliferative activated receptor gamma(PPARG).Molecular docking and molecular dynamics simulations revealed that the core ingredients bound well to the core targets.Animal experiments demonstrated that QLJXD effectively inhibited the expression of FABP4 and increased the expression of PPARG,thereby enhancing disorders of glycolipid metabolism.CONCLUSION:The putative therapeutic efficacy of QLJXD in the management of T2DM complicated with hyperlipidemia may be ascribed to the synergistic actions of multiple components,such as quercetin,β-sitosterol,wogonin,and baicalein,which collectively modulate FABP4 and PPARG molecular targets.
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.
