Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic...Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.展开更多
Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating ...Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.展开更多
To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemio...To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemiological methods and statistical analysis was used on data collected from the National Disease Reporting Information System between 2007 to 2011 and the National Active Surveillance System between 2007 and 2010. Our analysis shows that while the number of human rabies cases decreased year by year, the number of districts reporting cases did not show significant change. The situations in Guangdong, Guangxi, Guizhou and Hunan provinces clearly improved over the period but they remain provinces with high-incidence, and consequently influence the epidemic situation of surrounding provinces and possibly the whole country. Summer and autumn were high-incidence seasons. Farmers, students and pre-school children represent the high-risk populations, and rates of cases in farmers increased, those for students decreased, and pre-school children remained unchanged. Provinces with active surveillance programs reported a total of 2346 individual cases, of which 88.53% were associated with canines. Postexposure prophylaxis （PEP） of rabies cases was not significantly improved, whereas PEP in post-exposure population was good. In rural regions of China, canine density was reduced somewhat, and the immunization rate increased slightly. Finally we show that while the epidemic decreased 2007 to 2011 in China, cases continued to be diffused in certain regions. Lack of standardization of PEP on rabies eases was the main reason of morbidity. The high density and low immunization of dog in rural areas and the defective situation of PEP are still continuous occurrences in China and remain a cause for concern.展开更多
Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of...Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay （ELISA）. Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic （ROC）. The combined diagnosis model was established by logistic regression analysis. Results： The serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker. Conclusion： Serum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.展开更多
OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremor...OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.展开更多
Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms o...Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.展开更多
Background:Daidzein,phytoestrogens derived from the Pueraria lobata(Willd.)Ohwi root used in traditional Chinese medicine,has a wide range of biological activities,including antioxidant,anti-inflammatory,and neuroprot...Background:Daidzein,phytoestrogens derived from the Pueraria lobata(Willd.)Ohwi root used in traditional Chinese medicine,has a wide range of biological activities,including antioxidant,anti-inflammatory,and neuroprotection.However,the neuroprotective role of daidzein in oxygen-glucose deprivation/reperfusion injury and its underlying mechanism are still unknown.Methods:In this study,we used pheochromocytoma cells induced by oxygen-glucose deprivation and reperfusion to study the potential effect in the protection of the nerve cells.Then,we used molecular docking simulation and network pharmacology to predict the possible targets and pharmacological pathways of daidzein.Western blot was used to verify the expression of target proteins with or without adding the inhibitors.Results:After daidzein treatment,cell vitality had an upward trend(P<0.05)and the release of lactate dehydrogenase had a downward trend(P<0.01)in dose-dependent compared with the model group by exposure to oxygen-glucose deprivation and reperfusion.Several core targets were analyzed through network pharmacology and molecular docking including catalase,peroxisome proliferator-activated receptor gamma,vascular endothelial growth factor A,interleukin-6,tumor necrosis factor,nitric oxide synthase 3,prostaglandin-endoperoxide synthase 2,and RAC-alpha serine/threonine kinase 1.These results suggest that catalase may be a first-ranked target for the neuroprotective role of daidzein.Gene Ontology enrichment analysis indicated the pathways mainly contained molecule metabolic process,while Kyoto Encyclopedia of Genes and Genomes enrichment analysis focus on pathways in terms of inflammation such as tumor necrosis factor signal pathway.Then,Western blot results showed that daidzein had a significant increase on the expression of protein catalase(P<0.01).Daidzein reversed catalase level alterations after oxygen-glucose deprivation reperfusion injury in a dose-dependent manner which was consistent with the catalase antagonists-based experiments.Conclusion:These outcomes provide new insights into the neuroprotective effect and mechanism of daidzein in oxygen-glucose deprivation/reperfusion injury.展开更多
Background:Blood stasis syndrome is one of the major syndromes in the development of chronic conditions in traditional Chinese medicine.Blood stasis syndrome is closely related to microcirculation dysfunction and thro...Background:Blood stasis syndrome is one of the major syndromes in the development of chronic conditions in traditional Chinese medicine.Blood stasis syndrome is closely related to microcirculation dysfunction and thrombosis.Trigonaceae,as a representative traditional Chinese medicine for promoting blood circulation and removing blood stasis,there are many studies on its anticoagulant,antiplatelet aggregation and antithrombotic effects.Methods:Optimization of sparganin compounds,comprising sparganin A,sparganin B,and sparganin C for the characterization of drug pair effects against blood stasis syndrome was carried out.Ternary quadratic regression orthogonal combination design was carried out in a mouse model of blood stasis syndrome.The concentrations of thromboxane B2,plasminogen activator inhibitor 1,fibrinogen,and endothelin 1 were evaluated by enzyme linked immunosorbent assay.Thymus,hepatic,and spleen indices were also assessed.The outcomes of the evaluations aided in identifying optimum parameter values for the most favorable precipitation against blood stasis syndrome.Subsequently,Cytoscape 3.7.1 was used for network pharmacology to predict the key targets of sparganins and disease.Results:After sparganin A,sparganin B,and sparganin C treatment,hepatic had a downward trend,while spleen indices and thymus had an upward trend.Compared with the model group,thromboxane B2,endothelin 1,plasminogen activator inhibitor 1,and fibrinogen were decreased(P<0.05).The blood stasis syndrome model regression equation was extremely significant,and the correlation coefficient of R was 0.939,indicating that sparganin A,sparganin B and sparganin C were positively correlated at all levels.According to the dosage of these three factors and test results,the equation was fitted and the maximum values of the three sparganin in the corresponding dose range were obtained as follows:A=0.2982 mg/10g,B=0.1438 mg/10g,C=0.0417 mg/10g.Thus,the optimum parameters were found to be 0.298:0.144:0.042 for synergistic drug combinations of sparganin compounds sparganin A,sparganin B,and sparganin C in blood stasis syndrome.The possible key targets of sparganins included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.Conclusion:Our study for the first time found two novel cyclic peptide compounds sparganin B and sparganin C have an anti-blood stasis effect,and speculated sparganins key targets included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.展开更多
Background:RenShenJian decoction,a combination of Pueraria lobata(Willd.)Ohwi and Panax ginseng C.A.Mey,has been used in China since the Song Dynasty(960-1279 C.E.)to relieve symptoms of diabetes mellitus.However,the ...Background:RenShenJian decoction,a combination of Pueraria lobata(Willd.)Ohwi and Panax ginseng C.A.Mey,has been used in China since the Song Dynasty(960-1279 C.E.)to relieve symptoms of diabetes mellitus.However,the key compounds in RenShenJian that ameliorate insulin resistance remain unclear.This study identified the anti-diabetic compounds in RenShenJian by rescuing the decreased function of adenosine 5’-monophosphate-activated protein kinase(AMPK),sirtuin 3(SIRT3),or glucose transporter isoform 4(GLUT4).Methods:After streptozotocin-induced diabetic mice were treated with RenShenJian,fasting blood glucose levels and protein expression of SIRT3,p-AMPK,and AMPK were determined.Compounds from RenShenJian in plasma were monitored using multiple responses by liquid chromatography-mass spectrometry.Additionally,two insulin-resistant cell models were incubated with compounds identified in RenShenJian in the blood.Glucose uptake was determined using the fluorescent analog 2-(N-(7-nitrobenz-2-oxa-1,3-dia-xol-4-yl)amino)-2-deoxyglucose.Protein expression levels of p-AMPK,AMPK,SIRT3,and GLUT4 were detected by western blotting.Results:RenShenJian decreased FBG levels and upregulated SIRT3 expression and AMPK phosphorylation in diabetic mice.Thirteen RenShenJian extracts were identified in the blood,11 of which increased the ratios of 2-(N-(7-nitrobenz-2-oxa-1,3-dia-xol 4-yl)amino)-2-deoxyglucose uptake in two insulin-resistant cell models.Nine extracts increased AMPK phosphorylation,nine increased SIRT3 expression,and six elevated GLUT4 expression in palmitate-induced HepG2 cells.Five extracts-puerarin,puerarin 6″-O-xyloside,genistein,ginsenoside Rb1,and ginsenoside Rd-simultaneously activated AMPK,SIRT3 and GLUT4.Conclusion:A series of compounds in RenShenJian that target AMPK,SIRT3,and/or GLUT4 was confirmed and indicate the chemical material basis of amelioration of insulin resistance by RenShenJian.展开更多
Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based o...Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based on the 21 main active components of Resina Draconis previously analyzed by our group,the potential action targets of the active components were predicted and screened out by using the databases such as Swiss Target Prediction and Pharmapper.The genes corresponding to the related targets were retrieved by UniProt and GeneCards,and then the"component-target"network model was established using Cytoscape 3.9.1 software.The protein-protein interaction network was constructed by using STRING database for analysis.The STRING database was used for enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genome pathways to explore the underlying action mechanisms.Result:A total of 21 main analgesic active components of Resina Draconis and 77 intersecting targets of Resina Draconis and pain were screened out.PPI network analysis indicated that such targets as albumin(ALB),tumor necrosis factor(TNF),RAC-alpha serine/threonine-protein kinase 1(AKT1)and epidermal growth factor receptor(EGFR)might be the core targets of analgesia.Through gene ontology enrichment analysis,a total of 169 gene ontology entries were obtained(P<0.01),including 111 biological processes,31 molecular functions and 27 cellular components.Through enrichment analysis of KEGG pathways,a total of 112(P<0.01)signaling pathways were screened.Conclusion:Dracaenogenins A,Resveratrol and 7,4′-dihydroxyflavone in Resina Draconis may be the main material basis for analgesia,which can interact with multiple targets such as AlB,AKT1,TNF,and EGFR,and exerts analgesic effect through signaling pathways such as mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-Akt signaling pathway,and Rap1 signaling pathway.展开更多
Background： Damage of the medial prefrontal cortex （mPFC） results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson＇s disease （PD）. Since the course of mPFC damage is sti...Background： Damage of the medial prefrontal cortex （mPFC） results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson＇s disease （PD）. Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin （MT） on neurotoxicity in the mPFC of a rat model of PD. Methods： One hundred and fifty-four normal, male Wistar rats were randomly divided into the following five groups： normal ＋ normal saline （NS）, normal ＋ 6-hydroxydopamine （6-OHDA）, sham pinealectomy （PX） ＋ 6-OHDA, PX ＋ 6-OHDA, and MT ＋ 6-OHDA. 6-OHDA was injected into the right substantia nigra pars compacta （SNc） and ventral tegmental area （VTA） of each group, except normal ＋ NS, 60 days after the PX. In the MT treatment group, MT was administered immediately after the intraperitoneal injection at 4 p.m. every day, for 14 days. Neuronal apoptosis in the mPFC was exalnined using the TUNEL method, while the expression oftyrosine hydroxylase （TH）, Bax, and Bcl-2 in this region was measured using immunohistochemistry. The concentration of malondialdehyde （MDA） in the mPFC was examined using the thioharbituric acid method. Results： Rats in the normal ＋ 6-OHDA and sham PX ＋ 6-OHDA groups were combined into one group （Group N ＋ 6-OHDA） since there was no significant discrepancy between the groups for all the detected parameters. Apoptosis of cells in the NS, MT ＋ 6-OHDA, N ＋ 6-OH DA, and PX ＋ 6-OHDA groups was successively significantly increased （Hc = 256.25, P 〈 0.001 ）. The gray value of TH （＋） fibers in the NS, MT ＋ 6-OHDA, N ＋ 6-OHDA, and PX ＋ 6-OHDA groups was also successively significantly increased （F= 99.33, P 〈 0.001 ）. The staining intensities of Bax and Bcl-2 were as follows： Group NS ＋/＋, Group MT ＋ 6-OHDA ＋＋/＋, Group N ＋ 6-OHDA ＋＋/＋, and PX ＋ 6-OHDA ＋＋＋/＋. The concentrations of MDA in the NS, MT ＋ 6-OHDA, N ＋ 6-OHDA, and PX ＋ 6-OHDA groups were significantly increased in sequence （Hc = 296.309, P 〈 0.001 ）. Conclusions： Neuronal damage of the VTA by 6-OHDA might induce VTA-mPFC nerve fibers to undergo anterograde nerve damage, in turn inducing transneuronal damage of the mPFC. PX significantly exacerbated the neurotoxicity in the mPFC, which was induced by the neuronal injury of the VTA. However, MT replacement therapy significantly alleviated the neurotoxicity in the mPFC.展开更多
Objective： Crude Leonuri Fructus（CLF）, the fruits of the Leonurus japonicus Houtt, and processed Leonuri Fructus（PLF） by stir-baking as the important Chinese herbal medicines, have been used in China and other As...Objective： Crude Leonuri Fructus（CLF）, the fruits of the Leonurus japonicus Houtt, and processed Leonuri Fructus（PLF） by stir-baking as the important Chinese herbal medicines, have been used in China and other Asian countries for thousands of years. The objective of this research is to reveal the difference between CLF and PLF.Methods： The sensory technologies of the colorimetry, sensitive and validated HPLC-ELSD and GC combined with flame ionization detector（GC-FID） were employed to discriminate CLF and its processed product PLF. The color parameters of the samples were determined by colorimetric instrument CR-410. Moreover, the content of stachydrine and six fatty acids were determined by HPLC and GC. Subsequently,analysis of variance（ANOVA）, principal components analysis（PCA）, hierarchical cluster analysis（HCA）,and Kendall＇s correlation test were performed for data analysis.Results： The CLF and PLF were divided into two categories by PCA and HCA in terms of their component content and color. The results distinctly demonstrated significant changes in color and the content of indicative components between CLF and PLF.Conclusion： The study revealed that HPLC, GC, and colorimetric method in combination with chemometric method could be used as comprehensive quality evaluation for CLF and PLF.展开更多
Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallograp...Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallographic methods.Biological evaluation of these terpenoid dimers against renal fibrosis reveals that 5 inhibits extracellular matrix components including fibronectin and colla-gen I in a concentration-dependent manner.展开更多
基金funded by Scientific and Technological Planning Project of Guangzhou City(Grant No.201803010115)Projects of The National Natural Science Foundation of China(Grant No.82173972)+1 种基金2021 Traditional Chinese Medicine(Medicine of South China)Industry Talents Project-Innovation Team of South China Medicine Resources,Guangdong Provincial Basic and Applied Basic Research Fund(Grant No.2023A1515011147)supported by the Key Unit of Chinese Medicine Digitalization Quality Evaluation of State Administration of Traditional Chinese Medicine.
文摘Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.
基金supported by Projects of The National Natural Science Foundation of China(Grant No.82173972,82374172,82004086,81473413,81274060)The National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the 13th Five-year Plan Period(Grant No.2017ZX09301077)2021 Traditional Chinese Medicine(Medicine of South China)Industry Talents Project-Innovation Team of South China Medicine Resources,Guangdong Provincial Basic and Applied Basic Research Fund(Grant No.2023A1515011147).
文摘Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.
基金National Department Public Benefit Research Foundation(201103032)the Pathogens Network Monitoring Technology Research(2008ZX10004-008)
文摘To analyze features of the rabies epidemic in China between 2007 and 2011, identify factors influencing the epidemic and to provide a scientific basis for further control and prevention of rabies, Descriptive epidemiological methods and statistical analysis was used on data collected from the National Disease Reporting Information System between 2007 to 2011 and the National Active Surveillance System between 2007 and 2010. Our analysis shows that while the number of human rabies cases decreased year by year, the number of districts reporting cases did not show significant change. The situations in Guangdong, Guangxi, Guizhou and Hunan provinces clearly improved over the period but they remain provinces with high-incidence, and consequently influence the epidemic situation of surrounding provinces and possibly the whole country. Summer and autumn were high-incidence seasons. Farmers, students and pre-school children represent the high-risk populations, and rates of cases in farmers increased, those for students decreased, and pre-school children remained unchanged. Provinces with active surveillance programs reported a total of 2346 individual cases, of which 88.53% were associated with canines. Postexposure prophylaxis （PEP） of rabies cases was not significantly improved, whereas PEP in post-exposure population was good. In rural regions of China, canine density was reduced somewhat, and the immunization rate increased slightly. Finally we show that while the epidemic decreased 2007 to 2011 in China, cases continued to be diffused in certain regions. Lack of standardization of PEP on rabies eases was the main reason of morbidity. The high density and low immunization of dog in rural areas and the defective situation of PEP are still continuous occurrences in China and remain a cause for concern.
基金supported by a grant from the Provincial Research Project Funding of Guangxi,China (No. GSR 9817101)
文摘Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay （ELISA）. Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic （ROC）. The combined diagnosis model was established by logistic regression analysis. Results： The serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker. Conclusion： Serum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.
文摘OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.
基金supported by the Project of the Science and Technology Plan Project of Guangzhou(No.201803010115)the National Natural Science Foundation of China(No.82173972)the National Major“Significant New Drugs Development”during the Thirteenth Five-Year Plan Period(No.2017ZX09301077).
文摘Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.
基金supported by Projects of the National Natural Science Foundation of China(No.81773884,81473413,81274060,82004086)the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirteenth Five-year Plan Period(No.2017ZX09301077)the Science and Technology Plan Project of Guangzhou(No.201803010115)。
文摘Background:Daidzein,phytoestrogens derived from the Pueraria lobata(Willd.)Ohwi root used in traditional Chinese medicine,has a wide range of biological activities,including antioxidant,anti-inflammatory,and neuroprotection.However,the neuroprotective role of daidzein in oxygen-glucose deprivation/reperfusion injury and its underlying mechanism are still unknown.Methods:In this study,we used pheochromocytoma cells induced by oxygen-glucose deprivation and reperfusion to study the potential effect in the protection of the nerve cells.Then,we used molecular docking simulation and network pharmacology to predict the possible targets and pharmacological pathways of daidzein.Western blot was used to verify the expression of target proteins with or without adding the inhibitors.Results:After daidzein treatment,cell vitality had an upward trend(P<0.05)and the release of lactate dehydrogenase had a downward trend(P<0.01)in dose-dependent compared with the model group by exposure to oxygen-glucose deprivation and reperfusion.Several core targets were analyzed through network pharmacology and molecular docking including catalase,peroxisome proliferator-activated receptor gamma,vascular endothelial growth factor A,interleukin-6,tumor necrosis factor,nitric oxide synthase 3,prostaglandin-endoperoxide synthase 2,and RAC-alpha serine/threonine kinase 1.These results suggest that catalase may be a first-ranked target for the neuroprotective role of daidzein.Gene Ontology enrichment analysis indicated the pathways mainly contained molecule metabolic process,while Kyoto Encyclopedia of Genes and Genomes enrichment analysis focus on pathways in terms of inflammation such as tumor necrosis factor signal pathway.Then,Western blot results showed that daidzein had a significant increase on the expression of protein catalase(P<0.01).Daidzein reversed catalase level alterations after oxygen-glucose deprivation reperfusion injury in a dose-dependent manner which was consistent with the catalase antagonists-based experiments.Conclusion:These outcomes provide new insights into the neuroprotective effect and mechanism of daidzein in oxygen-glucose deprivation/reperfusion injury.
基金This work was supported by the National Natural Science Foundation of China(No.81773884,81473413,81274060)the National Science and Technology Major Project(No.2017ZX09301077)+1 种基金Guangzhou Science and Technology Project(No.201803010115)Technology Funds were obtained from the Key Unit of Chinese Medicine Digitalization Quality Evaluation of State Administration of Traditional Chinese Medicine.
文摘Background:Blood stasis syndrome is one of the major syndromes in the development of chronic conditions in traditional Chinese medicine.Blood stasis syndrome is closely related to microcirculation dysfunction and thrombosis.Trigonaceae,as a representative traditional Chinese medicine for promoting blood circulation and removing blood stasis,there are many studies on its anticoagulant,antiplatelet aggregation and antithrombotic effects.Methods:Optimization of sparganin compounds,comprising sparganin A,sparganin B,and sparganin C for the characterization of drug pair effects against blood stasis syndrome was carried out.Ternary quadratic regression orthogonal combination design was carried out in a mouse model of blood stasis syndrome.The concentrations of thromboxane B2,plasminogen activator inhibitor 1,fibrinogen,and endothelin 1 were evaluated by enzyme linked immunosorbent assay.Thymus,hepatic,and spleen indices were also assessed.The outcomes of the evaluations aided in identifying optimum parameter values for the most favorable precipitation against blood stasis syndrome.Subsequently,Cytoscape 3.7.1 was used for network pharmacology to predict the key targets of sparganins and disease.Results:After sparganin A,sparganin B,and sparganin C treatment,hepatic had a downward trend,while spleen indices and thymus had an upward trend.Compared with the model group,thromboxane B2,endothelin 1,plasminogen activator inhibitor 1,and fibrinogen were decreased(P<0.05).The blood stasis syndrome model regression equation was extremely significant,and the correlation coefficient of R was 0.939,indicating that sparganin A,sparganin B and sparganin C were positively correlated at all levels.According to the dosage of these three factors and test results,the equation was fitted and the maximum values of the three sparganin in the corresponding dose range were obtained as follows:A=0.2982 mg/10g,B=0.1438 mg/10g,C=0.0417 mg/10g.Thus,the optimum parameters were found to be 0.298:0.144:0.042 for synergistic drug combinations of sparganin compounds sparganin A,sparganin B,and sparganin C in blood stasis syndrome.The possible key targets of sparganins included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.Conclusion:Our study for the first time found two novel cyclic peptide compounds sparganin B and sparganin C have an anti-blood stasis effect,and speculated sparganins key targets included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.
基金supported by grants from National Natural Science Foundation of China(81773884)National Science and Technology Major Project(2017ZX09301077)+1 种基金Administration of Traditional Chinese Medicine of Guangdong Province(No.20201195)Guangdong Medical Science Foundation(No.B20191067).
文摘Background:RenShenJian decoction,a combination of Pueraria lobata(Willd.)Ohwi and Panax ginseng C.A.Mey,has been used in China since the Song Dynasty(960-1279 C.E.)to relieve symptoms of diabetes mellitus.However,the key compounds in RenShenJian that ameliorate insulin resistance remain unclear.This study identified the anti-diabetic compounds in RenShenJian by rescuing the decreased function of adenosine 5’-monophosphate-activated protein kinase(AMPK),sirtuin 3(SIRT3),or glucose transporter isoform 4(GLUT4).Methods:After streptozotocin-induced diabetic mice were treated with RenShenJian,fasting blood glucose levels and protein expression of SIRT3,p-AMPK,and AMPK were determined.Compounds from RenShenJian in plasma were monitored using multiple responses by liquid chromatography-mass spectrometry.Additionally,two insulin-resistant cell models were incubated with compounds identified in RenShenJian in the blood.Glucose uptake was determined using the fluorescent analog 2-(N-(7-nitrobenz-2-oxa-1,3-dia-xol-4-yl)amino)-2-deoxyglucose.Protein expression levels of p-AMPK,AMPK,SIRT3,and GLUT4 were detected by western blotting.Results:RenShenJian decreased FBG levels and upregulated SIRT3 expression and AMPK phosphorylation in diabetic mice.Thirteen RenShenJian extracts were identified in the blood,11 of which increased the ratios of 2-(N-(7-nitrobenz-2-oxa-1,3-dia-xol 4-yl)amino)-2-deoxyglucose uptake in two insulin-resistant cell models.Nine extracts increased AMPK phosphorylation,nine increased SIRT3 expression,and six elevated GLUT4 expression in palmitate-induced HepG2 cells.Five extracts-puerarin,puerarin 6″-O-xyloside,genistein,ginsenoside Rb1,and ginsenoside Rd-simultaneously activated AMPK,SIRT3 and GLUT4.Conclusion:A series of compounds in RenShenJian that target AMPK,SIRT3,and/or GLUT4 was confirmed and indicate the chemical material basis of amelioration of insulin resistance by RenShenJian.
基金supported by National Natural Science Foundation of China(No.82074137)Guangdong Basic and Applied Basic Research Foundation(No.2020A1515011515)Guangdong Undergraduate Innovation and Entrepreneurship Training Program(No.S202210573050).
文摘Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based on the 21 main active components of Resina Draconis previously analyzed by our group,the potential action targets of the active components were predicted and screened out by using the databases such as Swiss Target Prediction and Pharmapper.The genes corresponding to the related targets were retrieved by UniProt and GeneCards,and then the"component-target"network model was established using Cytoscape 3.9.1 software.The protein-protein interaction network was constructed by using STRING database for analysis.The STRING database was used for enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genome pathways to explore the underlying action mechanisms.Result:A total of 21 main analgesic active components of Resina Draconis and 77 intersecting targets of Resina Draconis and pain were screened out.PPI network analysis indicated that such targets as albumin(ALB),tumor necrosis factor(TNF),RAC-alpha serine/threonine-protein kinase 1(AKT1)and epidermal growth factor receptor(EGFR)might be the core targets of analgesia.Through gene ontology enrichment analysis,a total of 169 gene ontology entries were obtained(P<0.01),including 111 biological processes,31 molecular functions and 27 cellular components.Through enrichment analysis of KEGG pathways,a total of 112(P<0.01)signaling pathways were screened.Conclusion:Dracaenogenins A,Resveratrol and 7,4′-dihydroxyflavone in Resina Draconis may be the main material basis for analgesia,which can interact with multiple targets such as AlB,AKT1,TNF,and EGFR,and exerts analgesic effect through signaling pathways such as mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-Akt signaling pathway,and Rap1 signaling pathway.
文摘Background： Damage of the medial prefrontal cortex （mPFC） results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson＇s disease （PD）. Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin （MT） on neurotoxicity in the mPFC of a rat model of PD. Methods： One hundred and fifty-four normal, male Wistar rats were randomly divided into the following five groups： normal ＋ normal saline （NS）, normal ＋ 6-hydroxydopamine （6-OHDA）, sham pinealectomy （PX） ＋ 6-OHDA, PX ＋ 6-OHDA, and MT ＋ 6-OHDA. 6-OHDA was injected into the right substantia nigra pars compacta （SNc） and ventral tegmental area （VTA） of each group, except normal ＋ NS, 60 days after the PX. In the MT treatment group, MT was administered immediately after the intraperitoneal injection at 4 p.m. every day, for 14 days. Neuronal apoptosis in the mPFC was exalnined using the TUNEL method, while the expression oftyrosine hydroxylase （TH）, Bax, and Bcl-2 in this region was measured using immunohistochemistry. The concentration of malondialdehyde （MDA） in the mPFC was examined using the thioharbituric acid method. Results： Rats in the normal ＋ 6-OHDA and sham PX ＋ 6-OHDA groups were combined into one group （Group N ＋ 6-OHDA） since there was no significant discrepancy between the groups for all the detected parameters. Apoptosis of cells in the NS, MT ＋ 6-OHDA, N ＋ 6-OH DA, and PX ＋ 6-OHDA groups was successively significantly increased （Hc = 256.25, P 〈 0.001 ）. The gray value of TH （＋） fibers in the NS, MT ＋ 6-OHDA, N ＋ 6-OHDA, and PX ＋ 6-OHDA groups was also successively significantly increased （F= 99.33, P 〈 0.001 ）. The staining intensities of Bax and Bcl-2 were as follows： Group NS ＋/＋, Group MT ＋ 6-OHDA ＋＋/＋, Group N ＋ 6-OHDA ＋＋/＋, and PX ＋ 6-OHDA ＋＋＋/＋. The concentrations of MDA in the NS, MT ＋ 6-OHDA, N ＋ 6-OHDA, and PX ＋ 6-OHDA groups were significantly increased in sequence （Hc = 296.309, P 〈 0.001 ）. Conclusions： Neuronal damage of the VTA by 6-OHDA might induce VTA-mPFC nerve fibers to undergo anterograde nerve damage, in turn inducing transneuronal damage of the mPFC. PX significantly exacerbated the neurotoxicity in the mPFC, which was induced by the neuronal injury of the VTA. However, MT replacement therapy significantly alleviated the neurotoxicity in the mPFC.
基金financially supported by the project of national drug standards program,a Study Program on Standardization of Chinese Medicine Processing(No.201207004-7)the National Natural Science Foundation of China(No.81302745,81473352)+1 种基金The Guangzhou Science and Technology planningproject(No.201707010170)Guangdong Province Office of Education(No.2016KTSCX064)
文摘Objective： Crude Leonuri Fructus（CLF）, the fruits of the Leonurus japonicus Houtt, and processed Leonuri Fructus（PLF） by stir-baking as the important Chinese herbal medicines, have been used in China and other Asian countries for thousands of years. The objective of this research is to reveal the difference between CLF and PLF.Methods： The sensory technologies of the colorimetry, sensitive and validated HPLC-ELSD and GC combined with flame ionization detector（GC-FID） were employed to discriminate CLF and its processed product PLF. The color parameters of the samples were determined by colorimetric instrument CR-410. Moreover, the content of stachydrine and six fatty acids were determined by HPLC and GC. Subsequently,analysis of variance（ANOVA）, principal components analysis（PCA）, hierarchical cluster analysis（HCA）,and Kendall＇s correlation test were performed for data analysis.Results： The CLF and PLF were divided into two categories by PCA and HCA in terms of their component content and color. The results distinctly demonstrated significant changes in color and the content of indicative components between CLF and PLF.Conclusion： The study revealed that HPLC, GC, and colorimetric method in combination with chemometric method could be used as comprehensive quality evaluation for CLF and PLF.
基金This study was supported financially by the National Science Fund for Distinguished Young Scholars(No.81525026)the National Key R&D Program of China(No.2017YFA0503900)+3 种基金the She nzhe n Fundame ntal Research Program(No.JCYJ20200109114003921)the SZU Top Ranking Project(No.86000000210)the Natural Science Research Project of Shenzhen University(2019122)the SZU Medical Young Scientist Program.
文摘Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallographic methods.Biological evaluation of these terpenoid dimers against renal fibrosis reveals that 5 inhibits extracellular matrix components including fibronectin and colla-gen I in a concentration-dependent manner.
