It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine(TCM), which has been utilized in China for more than four millennia...It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine(TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance(NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs.展开更多
The emerging development of Extractive Reference Substance (ERS) is a methodology that meets the needs for quality control for Chinese Herbal Medicines (CHM) and respects the holistic viewpoint of Traditional Chinese ...The emerging development of Extractive Reference Substance (ERS) is a methodology that meets the needs for quality control for Chinese Herbal Medicines (CHM) and respects the holistic viewpoint of Traditional Chinese Medicine (TCM) and its clinical use of multiple ingredients with synergistic effects. The convention of using just a selected few Chemical Reference Substances (CRS) cannot adequately assess the quality of intact CHM. A validated chemical spectrum of an ERS provides the global characteristics in order to more specifically identify and assess targeted CHM. This paper describes the fundamental concepts, potential significance, and basic criteria of ERS, along with methods of preparation and calibration. Given the diversity of CHM, the various problems that will occur in establishing the proper process of ERS will need to be solved in a step by step manner. The ERSs of Ziziphi spinosae semen and ERS of Fritillaria thunbergii bulbus are given as examples of the development of ERS and demonstrate why we are optimistic about the utility of this approach.展开更多
Gastric cancer(GC)is characterized by high morbidity and mortality rates.Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis(Lour.)Gilg.,traditionally utilized for treating asthma,cardiac ischem...Gastric cancer(GC)is characterized by high morbidity and mortality rates.Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis(Lour.)Gilg.,traditionally utilized for treating asthma,cardiac ischemia,and tumors.However,comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited.In this study,Chinese agarwood petroleum ether extract(CAPEE)demonstrated potent cytotoxicity against human GC cells,with half maximal inhibitory concentration(IC_(50))values for AGS,HGC27,and MGC803 cells of 2.89,2.46,and 2.37μg·mL^(−1),respectively,at 48 h.CAPEE significantly induced apoptosis in these GC cells,with B-cell lymphoma-2(BCL-2)associated X protein(BAX)/BCL-2 antagonist killer 1(BAK)likely mediating CAPEE-induced apoptosis.Furthermore,CAPEE induced G_(0)/G_(1)phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid(DNA)damage-p21-cyclin D1/cyclin-dependent kinase 4(CDK4)signaling axis,and increased Fe^(2+),lipid peroxides and reactive oxygen species(ROS)levels,thereby inducing ferroptosis.Ribonucleic acid(RNA)sequencing,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1(HO-1)in human GC cells.RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells.Additionally,CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues.These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis,suggesting its potential as a candidate drug for GC treatment.展开更多
Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the trea...Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.展开更多
Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain cha...Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.展开更多
Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-a...Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.展开更多
AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extra...AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD. METHOD: Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge. Madecassoside was used as the internal standard(IS). Chromatographic separation was achieved on an ODS column(100 mm × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of acetonitrile/water(30 : 70, V/V) containing 0.1 mmol L 1ammonium acetate at a flow rate of 0.25 mL min 1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min. The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6→469.2 for PD and of m/z 973.6→469.2 for madecassoside(IS), respectively. RESULTS: The calibration curve was linear from 5 to 2 000 ng mL 1(r2>0.99) with a lower limit of quantification(LLOQ) of 5 ng mL 1. The intra- and inter-day precision(relative standard deviation, RSD) values were below 15% and the accuracy(relative error, RE) was from 15% to +15% at three quality control(QC) levels. Plasma concentrations of PD were determined for 24 h after i.v. administration of PD, and oral administration of PD and PRE, respectively. The absolute oral bioavailability of PD in rats was found to be(0.48 ± 0.19)% when administered PD, and to be(1.81 ± 0.89)% when administered PRE. CONCLUSION: The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.展开更多
The quality of Astragali Radix(AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the ...The quality of Astragali Radix(AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years’ wild Astragali Radix(WAR) and transplanted Astragali Radix(TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1–6 growth years root through the methods. The contents of flavonoids and saponins in 2–6 growth years’ WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR(4-year-old)and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters(EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.展开更多
OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herba...OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.展开更多
Objective:This study investigated the antidepression mechanisms of Xiaoyaosan(XYS),a classic Chinese prescription,from the perspective of energy metabolism in the brain and intestinal tissues.Methods:Chronic unpredict...Objective:This study investigated the antidepression mechanisms of Xiaoyaosan(XYS),a classic Chinese prescription,from the perspective of energy metabolism in the brain and intestinal tissues.Methods:Chronic unpredictable mild stress model-a classic depression rat model-was established.Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated.Effects of XYS on energetic charge(EC),adenosine triphosphate-related enzymes,and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using highperformance liquid chromatography,biochemical analysis,and real-time quantitative polymerase chain reaction,respectively.Spearman correlation analysis was conducted to construct a correlation network of"behavior-brain energy metabolism-intestinal energy metabolism"of depression.Results:XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na+-K+-adenosine triphosphatase(ATPase)and Ca2+-Mg2+-ATPase in hippocampus and jejunum tissues of depressed rats.XYS restored the key energetic pathways that had been interrupted by depression,including glycolysis,tricarboxylic acid cycle,and oxidative phosphorylation.Furthermore,XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine.Conclusion:XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues,alleviating both core and concomitant symptoms of depression.The current findings underscore the role of energy metabolism in the antidepressive activity of XYS,providing a fresh perspective on depression,and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.展开更多
Ulcerative colitis(UC)is an idiopathic,relapsing,and etiologically complicated chronic inflammatory bowel disease.Despite substantial progress in the management of UC,the outcomes of mucosal barrier repair are unsatis...Ulcerative colitis(UC)is an idiopathic,relapsing,and etiologically complicated chronic inflammatory bowel disease.Despite substantial progress in the management of UC,the outcomes of mucosal barrier repair are unsatisfactory.In this study,phillygenin(PHI)treatment alleviated the symptoms of chronic colitis in mice,including body weight loss,severe disease activity index scores,colon shortening,splenomegaly,oxidative stress,and inflammatory response.In particular,PHI treatment ameliorated the tight junction proteins(TJs)reduction,fibrosis,apoptosis,and intestinal stem cell activity,indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis.In the NCM460 cells damage model,dextran sulfate sodium triggered the sequential induction of TJs reduction,fibrosis,and apoptosis.Takeda G protein-coupled receptor-5(TGR5)dysfunction mediated NCM460 cell injury.Moreover,PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function,depending on TGR5 activation.PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids.Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5,indicating that PHI is an agonist of TGR5.The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca^(2+) release was involved in NCM460 cell injury as well,which was associated with TGR5 dysfunction.When NCM460 cells were pretreated with PHI,the PERK-eIF2α pathway and elevated Ca^(2+) levels were blocked.In conclusion,our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca^(2+) pathway through TGR5 activation to against DSS-induced TJs reduction,fibrosis,and apoptosis.展开更多
Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold ...Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.展开更多
Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvas...Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.展开更多
Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuropr...Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-Ⅲ on corticosterone injured rat phaeochromocytoma(PC12) cells. Our results demonstrate that ATL-Ⅲ increases cell viability and reduces the release of lactate dehydrogenase(LDH). The results suggest that ATL-Ⅲ protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca^(2+) overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-κB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-Ⅲ protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-Ⅲ may serve as a therapeutic agent in the treatment of depression.展开更多
Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific in...Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific ingredients have been found in Ephedra herb, mainly including alkaloids, flavonoids, tannins, polysaccharides, organic acids, volatile oils, and many other active compounds. These components from Ephedra herb account for its use as the accurate treatment of cold, cough, cardiovascular and immune system disease, cancer, microbial infection, and other diseases. Moreover, with the fast development of novel chemistry and medicine technology, new chemical constituents and pharmacological effects of Ephedra herb are increasingly identified, demonstrating their great potential for various diseases treatment. Therefore, further detailed understanding and investigation of this ancient herb will offer new opportunities to develop novel therapeutics. This study systematically reviews its progress of phytochemistry, traditional and modern pharmacology based on research data that have been reported, aiming at providing useful insight for commercial exploitation, further study and precision medication of Ephedra herb in future.展开更多
Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics stud...Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control(NC)and para-chlorophenylalanine(PCPA)-induced insomnia model(IM)rats that were orally administered the aqueous extract of ZSS.An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass(UHPLC-Q-Orbitrap-MS)method was developed and validated for the simultaneous determination of coclaurine,magnoflorine,spinosin,6000-feruloylspinosin,jujuboside A(JuA),and jujuboside B(JuB)in ZSS in rat plasma.The established approach was successfully applied to a comparative pharmacokinetic study.The systemic exposures of spinosin and 6000-feruloylspinosin were decreased in the IM group compared to the NC group,while plasma clearance(CL)was significantly increased.The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats.The T1/2 of JuA in the IM group was significantly accelerated.The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups.These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin,6000-feruloylspinosin,JuA,and JuB in the ZSS aqueous extract,providing an experimental basis for the role of ZSS in insomnia treatment.The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.展开更多
Astragali Radix(AR) is one of the most popular herbal medicines in traditional Chinese medicine(TCM). Wild AR is believed to be of high quality, and substitution with cultivated AR is frequently encountered in the mar...Astragali Radix(AR) is one of the most popular herbal medicines in traditional Chinese medicine(TCM). Wild AR is believed to be of high quality, and substitution with cultivated AR is frequently encountered in the market. In the present study, two types of ARs(wild and cultivated) from Astragalus membranaceus(Fisch.) Bge. and A. membranaceus var. mongholicus(Bge.) Hsiao, growing in different regions of China, were analyzed by NMR profiling coupled with multivariate analysis. Results showed that both could be differentiated successfully and cultivation patterns or growing years might have greater impact on the metabolite compositions than the variety; the metabolites responsible for the separation were identified. In addition, three extraction methods were compared and the method(M1) was used for further analysis. In M1, the extraction solvent composed of water, methanol, and chloroform in the ratio of 1 : 1 : 2 was used to obtain the aqueous methanol(upper layer) and chloroform(lower layer) fractions, respectively, showing the best separation. The differential metabolites among different methods were also revealed. Moreover, the sucrose/glucose ratio could be used as a simple index to differentiate wild and cultivated AR. Meanwhile, the changes of correlation pattern among the differential metabolites of the two varieties were found. The work demonstrated that NMR-based non-targeted profiling approach, combined with multivariate statistical analysis, can be used as a powerful tool for differentiating AR of different cultivation types or growing years.展开更多
AIM:To investigate the chemical constituents of the roots of Polygala sibirica L.(Polygalaceae) METHOD:The isolation was performed by solvent extraction and various chromatographic techniques,including silica gel,Seph...AIM:To investigate the chemical constituents of the roots of Polygala sibirica L.(Polygalaceae) METHOD:The isolation was performed by solvent extraction and various chromatographic techniques,including silica gel,Sephadex LH-20,ODS,semi-preparative HPLC,and preparative TLC.The chemical structures were elucidated based on extensive spectroscopic analysis,including HR-ESI-MS and 1D- and 2D-NMR spectroscopic data.RESULTS:A total of sixteen compounds,including five xanthones(5,7–10),five saccharide esters(1,3,4,12,13),two flavonoids(14,16),two triterpenoids(11,15),one phenylpropanoid(6),and one benzophenone glycoside(2) were isolated.Their structures were determined as sibiricose A7(1),sibiriphenone A(2),polygalatenoside A(3),polygalatenoside C(4),lancerin(5),3,4,5-trimethoxycinnamic acid(6),6-hydroxy-1,2,3,7-tetramethoxyxanthone(7),1,3,7-trihydroxy-2-methoxyxanthone(8),onjixanthone II(9),1,2,3,6,7-pentamethoxyxanthone(10),presenegenin(11),3'-O-3,4,5-trimethoxycinnamoyl-6-O-4-methoxy benzoyl sucrose(12),tenuifoliside C(13),5,3'-dihydroxy-7,4'-dimethoxyflavonol-3-O-β-D-glucopyranoside(14),tenuifolin(15),and rhamnetin 3-O-β-D-glucopyranoside(16).CONCLUSION:Compounds 1 and 2 are two new compounds from P.sibirica.展开更多
Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an...Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.展开更多
Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. T...Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance(NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.展开更多
基金supported by the Science and Technology Innovation Team of Shanxi Province(No.2013131015)Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi(OIT)
文摘It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine(TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance(NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs.
文摘The emerging development of Extractive Reference Substance (ERS) is a methodology that meets the needs for quality control for Chinese Herbal Medicines (CHM) and respects the holistic viewpoint of Traditional Chinese Medicine (TCM) and its clinical use of multiple ingredients with synergistic effects. The convention of using just a selected few Chemical Reference Substances (CRS) cannot adequately assess the quality of intact CHM. A validated chemical spectrum of an ERS provides the global characteristics in order to more specifically identify and assess targeted CHM. This paper describes the fundamental concepts, potential significance, and basic criteria of ERS, along with methods of preparation and calibration. Given the diversity of CHM, the various problems that will occur in establishing the proper process of ERS will need to be solved in a step by step manner. The ERSs of Ziziphi spinosae semen and ERS of Fritillaria thunbergii bulbus are given as examples of the development of ERS and demonstrate why we are optimistic about the utility of this approach.
基金supported by the Natural Science Foundation of Beijing City(No.J230034)the Fundamental Research Funds for the Central Universities(No.2023-JYB-JBQN-051)the Talent Cultivation Project of Beijing University of Chinese Medicine(No.JZPY202206).
文摘Gastric cancer(GC)is characterized by high morbidity and mortality rates.Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis(Lour.)Gilg.,traditionally utilized for treating asthma,cardiac ischemia,and tumors.However,comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited.In this study,Chinese agarwood petroleum ether extract(CAPEE)demonstrated potent cytotoxicity against human GC cells,with half maximal inhibitory concentration(IC_(50))values for AGS,HGC27,and MGC803 cells of 2.89,2.46,and 2.37μg·mL^(−1),respectively,at 48 h.CAPEE significantly induced apoptosis in these GC cells,with B-cell lymphoma-2(BCL-2)associated X protein(BAX)/BCL-2 antagonist killer 1(BAK)likely mediating CAPEE-induced apoptosis.Furthermore,CAPEE induced G_(0)/G_(1)phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid(DNA)damage-p21-cyclin D1/cyclin-dependent kinase 4(CDK4)signaling axis,and increased Fe^(2+),lipid peroxides and reactive oxygen species(ROS)levels,thereby inducing ferroptosis.Ribonucleic acid(RNA)sequencing,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1(HO-1)in human GC cells.RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells.Additionally,CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues.These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis,suggesting its potential as a candidate drug for GC treatment.
基金the National Natural Science Foundation of China(82222075).
文摘Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.
基金supported by the National Natural Science Foundation of China(No.81973466)the National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Support Project,and the Program of Graduate Innovation Research in Shanxi Province(No.2023KY019).
文摘Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.
基金supported by the Natural Science Foundation of State(Nos.81603289 and 81603251)the Base Program of the Joint Training Talents of Shanxi Province(No.2017JD01)the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No.201605D111004)
文摘Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.
基金supported by the National Natural Science Foundation of China(No.81073030)the National Key Technology R&D Program in the 11th Five Year Plan of China(No.2008BA151B00-2)
文摘AIMS: To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma, and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD. METHOD: Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge. Madecassoside was used as the internal standard(IS). Chromatographic separation was achieved on an ODS column(100 mm × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of acetonitrile/water(30 : 70, V/V) containing 0.1 mmol L 1ammonium acetate at a flow rate of 0.25 mL min 1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min. The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6→469.2 for PD and of m/z 973.6→469.2 for madecassoside(IS), respectively. RESULTS: The calibration curve was linear from 5 to 2 000 ng mL 1(r2>0.99) with a lower limit of quantification(LLOQ) of 5 ng mL 1. The intra- and inter-day precision(relative standard deviation, RSD) values were below 15% and the accuracy(relative error, RE) was from 15% to +15% at three quality control(QC) levels. Plasma concentrations of PD were determined for 24 h after i.v. administration of PD, and oral administration of PD and PRE, respectively. The absolute oral bioavailability of PD in rats was found to be(0.48 ± 0.19)% when administered PD, and to be(1.81 ± 0.89)% when administered PRE. CONCLUSION: The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.
基金the National Key R&D Program of China(No.2019YFC1710800)China Postdoctoral Science Foundation Project(No.2019M650851)+3 种基金the National Natural Science Foundation of China(No.81872962)Science and Technology Research Project of Shanxi Province(No.20150313004-5)Key Projects of Key Research and Development Plan in Shanxi(No.201603D311101)Shanxi Province Technology Innovation Project of Excellent Talent(Nos.201605D211030,201705D211020)。
文摘The quality of Astragali Radix(AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years’ wild Astragali Radix(WAR) and transplanted Astragali Radix(TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1–6 growth years root through the methods. The contents of flavonoids and saponins in 2–6 growth years’ WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR(4-year-old)and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters(EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.
文摘OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.
基金National Natural Science Foundation of China(No.82274360)the Traditional Chinese Medicine Scientific Research Project of Shanxi Province in 2024(No.2024ZYY2A032)+1 种基金the Research Project of Shanxi Scholarship Council of China(No.2022-026)the Traditional Chinese Medicine Innovation Team of Shanxi Province(No.zyytd2024020)。
文摘Objective:This study investigated the antidepression mechanisms of Xiaoyaosan(XYS),a classic Chinese prescription,from the perspective of energy metabolism in the brain and intestinal tissues.Methods:Chronic unpredictable mild stress model-a classic depression rat model-was established.Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated.Effects of XYS on energetic charge(EC),adenosine triphosphate-related enzymes,and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using highperformance liquid chromatography,biochemical analysis,and real-time quantitative polymerase chain reaction,respectively.Spearman correlation analysis was conducted to construct a correlation network of"behavior-brain energy metabolism-intestinal energy metabolism"of depression.Results:XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na+-K+-adenosine triphosphatase(ATPase)and Ca2+-Mg2+-ATPase in hippocampus and jejunum tissues of depressed rats.XYS restored the key energetic pathways that had been interrupted by depression,including glycolysis,tricarboxylic acid cycle,and oxidative phosphorylation.Furthermore,XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine.Conclusion:XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues,alleviating both core and concomitant symptoms of depression.The current findings underscore the role of energy metabolism in the antidepressive activity of XYS,providing a fresh perspective on depression,and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.
基金supported by the National Natural Science Fund of China(Grant Nos.:31800293 and 32370422)Project of Standard for TCM(Grant No.:ZYBZH-Y-JIN-34).
文摘Ulcerative colitis(UC)is an idiopathic,relapsing,and etiologically complicated chronic inflammatory bowel disease.Despite substantial progress in the management of UC,the outcomes of mucosal barrier repair are unsatisfactory.In this study,phillygenin(PHI)treatment alleviated the symptoms of chronic colitis in mice,including body weight loss,severe disease activity index scores,colon shortening,splenomegaly,oxidative stress,and inflammatory response.In particular,PHI treatment ameliorated the tight junction proteins(TJs)reduction,fibrosis,apoptosis,and intestinal stem cell activity,indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis.In the NCM460 cells damage model,dextran sulfate sodium triggered the sequential induction of TJs reduction,fibrosis,and apoptosis.Takeda G protein-coupled receptor-5(TGR5)dysfunction mediated NCM460 cell injury.Moreover,PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function,depending on TGR5 activation.PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids.Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5,indicating that PHI is an agonist of TGR5.The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca^(2+) release was involved in NCM460 cell injury as well,which was associated with TGR5 dysfunction.When NCM460 cells were pretreated with PHI,the PERK-eIF2α pathway and elevated Ca^(2+) levels were blocked.In conclusion,our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca^(2+) pathway through TGR5 activation to against DSS-induced TJs reduction,fibrosis,and apoptosis.
基金supported by the National Natural Science Foundation of China(82274225)NATCM's Project of High-level Construction of Key TCM Disciplines-Beijing University of Chinese Medicine-Life Science from the Perspective of Chinese Medicine(zyyzdxk-2023263).
文摘Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.
基金supported the National Natural Science Foundation of China(81930113).
文摘Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
基金supported by the National Nature Science Foundation of China(No.81673572)the Applied basic research project of Shanxi Province(No.201601D021164)+2 种基金the Innovation project of higher education institutions in Shanxi Province(No.2016120)the Construction of the Science and Technology Basic Condition Platform of Shanxi Province(No.2014091022)the Program of Science and Technology of Shanxi Province(No.20140313008-14)
文摘Atractylenolide Ⅲ(ATL-Ⅲ), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-Ⅲ on corticosterone injured rat phaeochromocytoma(PC12) cells. Our results demonstrate that ATL-Ⅲ increases cell viability and reduces the release of lactate dehydrogenase(LDH). The results suggest that ATL-Ⅲ protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca^(2+) overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-κB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-Ⅲ protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-Ⅲ may serve as a therapeutic agent in the treatment of depression.
基金the National Natural Science Foundation of China (Nos.31670328,31270383)。
文摘Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific ingredients have been found in Ephedra herb, mainly including alkaloids, flavonoids, tannins, polysaccharides, organic acids, volatile oils, and many other active compounds. These components from Ephedra herb account for its use as the accurate treatment of cold, cough, cardiovascular and immune system disease, cancer, microbial infection, and other diseases. Moreover, with the fast development of novel chemistry and medicine technology, new chemical constituents and pharmacological effects of Ephedra herb are increasingly identified, demonstrating their great potential for various diseases treatment. Therefore, further detailed understanding and investigation of this ancient herb will offer new opportunities to develop novel therapeutics. This study systematically reviews its progress of phytochemistry, traditional and modern pharmacology based on research data that have been reported, aiming at providing useful insight for commercial exploitation, further study and precision medication of Ephedra herb in future.
基金This work was supported by grants from the National Natural Science Foundation of China(No:81603289,81603251)Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No:201605D111004)and Key Technology Research Zhen Dong Special Project from Shanxi Science and Technology Department(No:2016ZD0105).
文摘Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control(NC)and para-chlorophenylalanine(PCPA)-induced insomnia model(IM)rats that were orally administered the aqueous extract of ZSS.An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass(UHPLC-Q-Orbitrap-MS)method was developed and validated for the simultaneous determination of coclaurine,magnoflorine,spinosin,6000-feruloylspinosin,jujuboside A(JuA),and jujuboside B(JuB)in ZSS in rat plasma.The established approach was successfully applied to a comparative pharmacokinetic study.The systemic exposures of spinosin and 6000-feruloylspinosin were decreased in the IM group compared to the NC group,while plasma clearance(CL)was significantly increased.The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats.The T1/2 of JuA in the IM group was significantly accelerated.The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups.These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin,6000-feruloylspinosin,JuA,and JuB in the ZSS aqueous extract,providing an experimental basis for the role of ZSS in insomnia treatment.The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.
基金supported by the Ministry of Agriculture for providing New Application for Herbal Research Grant Scheme(NRGS)(No.NH1014D040)the National 12th 5-Year Science and Technology Support Program(No.2011BA107B01)+1 种基金the Science and Technology Innovation Team of Shanxi Province(No.2013131015)the National Natural Science Foundation of China(No.31570346)
文摘Astragali Radix(AR) is one of the most popular herbal medicines in traditional Chinese medicine(TCM). Wild AR is believed to be of high quality, and substitution with cultivated AR is frequently encountered in the market. In the present study, two types of ARs(wild and cultivated) from Astragalus membranaceus(Fisch.) Bge. and A. membranaceus var. mongholicus(Bge.) Hsiao, growing in different regions of China, were analyzed by NMR profiling coupled with multivariate analysis. Results showed that both could be differentiated successfully and cultivation patterns or growing years might have greater impact on the metabolite compositions than the variety; the metabolites responsible for the separation were identified. In addition, three extraction methods were compared and the method(M1) was used for further analysis. In M1, the extraction solvent composed of water, methanol, and chloroform in the ratio of 1 : 1 : 2 was used to obtain the aqueous methanol(upper layer) and chloroform(lower layer) fractions, respectively, showing the best separation. The differential metabolites among different methods were also revealed. Moreover, the sucrose/glucose ratio could be used as a simple index to differentiate wild and cultivated AR. Meanwhile, the changes of correlation pattern among the differential metabolites of the two varieties were found. The work demonstrated that NMR-based non-targeted profiling approach, combined with multivariate statistical analysis, can be used as a powerful tool for differentiating AR of different cultivation types or growing years.
基金financially supported by the National Key Technology R&D Program"New Drug Innovation"of China(Nos.2012ZX09301002-002-002,2012ZX09304-005)special funds for scientific research on traditional Chinese medicine(No.201307002)National Science Fund for Excellent Young Scholars(No.81222051)
文摘AIM:To investigate the chemical constituents of the roots of Polygala sibirica L.(Polygalaceae) METHOD:The isolation was performed by solvent extraction and various chromatographic techniques,including silica gel,Sephadex LH-20,ODS,semi-preparative HPLC,and preparative TLC.The chemical structures were elucidated based on extensive spectroscopic analysis,including HR-ESI-MS and 1D- and 2D-NMR spectroscopic data.RESULTS:A total of sixteen compounds,including five xanthones(5,7–10),five saccharide esters(1,3,4,12,13),two flavonoids(14,16),two triterpenoids(11,15),one phenylpropanoid(6),and one benzophenone glycoside(2) were isolated.Their structures were determined as sibiricose A7(1),sibiriphenone A(2),polygalatenoside A(3),polygalatenoside C(4),lancerin(5),3,4,5-trimethoxycinnamic acid(6),6-hydroxy-1,2,3,7-tetramethoxyxanthone(7),1,3,7-trihydroxy-2-methoxyxanthone(8),onjixanthone II(9),1,2,3,6,7-pentamethoxyxanthone(10),presenegenin(11),3'-O-3,4,5-trimethoxycinnamoyl-6-O-4-methoxy benzoyl sucrose(12),tenuifoliside C(13),5,3'-dihydroxy-7,4'-dimethoxyflavonol-3-O-β-D-glucopyranoside(14),tenuifolin(15),and rhamnetin 3-O-β-D-glucopyranoside(16).CONCLUSION:Compounds 1 and 2 are two new compounds from P.sibirica.
基金This study is funded by the National Nature Science Foundation of China(Grant Nos.:82074323,and 81673572)Key Research and Development Program of Shanxi Province(Program No.:202102130501010)+2 种基金The major science and technology project for“Significant New Drugs Creation”(Project No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Project No.:2020019)The special fund for Science and Technology Innovation Teams of Shanxi Province(Grant No.:202204051002011).
文摘Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
基金supported by the National Natural Science Foundation of China(No.81441096)the Project of Science and Technology of Shanxi Province(201603D321077)+1 种基金the Key Laboratory of Shanxi Province(201605D111004)the Science and Technology Innovation Team of Shanxi Province(201605D131045-18)
文摘Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance(NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.
