The California Chinese Medicine and Acupuncture Research Association,founded on March 25,1974,is the first Chinese medicine organization registered with the state government in California.It was established after more...The California Chinese Medicine and Acupuncture Research Association,founded on March 25,1974,is the first Chinese medicine organization registered with the state government in California.It was established after more than a year of arduous preparation and had 15 founding members.Over time,it evolved into the biggest organization of Chinese medicine and acupuncture in California.And in 2015,it became the American Association of Chinese Medicine and Acupuncture with more than 500 members.展开更多
Due to the multitudinous structural types of glycosylated components,accurate identification of glycosylation modifications and secondary metabolite structures in herbs remains a challenge for natural drug analysis an...Due to the multitudinous structural types of glycosylated components,accurate identification of glycosylation modifications and secondary metabolite structures in herbs remains a challenge for natural drug analysis and new drug discovery[1].To solve this problem,we developed an auxiliary spectral analysis strategy based on Glyco-GNN machine learning techniques(Fig.1).It is named as“Glycomol”,an auxiliary tool for the identification of glycoside molecules.In Glycomol,the structure of glycosylated components was analyzed in terms of parent nucleus,glycan modification sites,and glycan types.Saponins were taken as representative glycosylated components due to their high structural complexity.To estimate the likelihood of results from this modularization strategy,first we extracted the liquid phase and mass spectrum information of 96 structure-known saponins from multi-stage mass spectrometry data.Then,24 standard saponins were applied for analysis and a 95.8%hit rate was achieved.展开更多
Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for ...Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for four weeks to induce hyperlipidemia,then 16S rRNA sequencing was used to compare the intestinal flora between hyperlipidemic and control diet-fed rats.Results:The microbiome of rats fed an HFD for four weeks differed from that of control diet-fed rats.Bacterial species that were less abundant were most affected by HFD feeding,among which were many pathogenic species,which became significantly more abundant.Eighteen genera were present in significantly different numbers in hyperlipidemic and control rats,more than half of which have been linked to infection and inflammation,or energy intake and obesity.The results indicated a type of stress response of the flora to a high-fat environment.In addition,the age of the rats tended to influence the gut microbial composition.Conclusion:These findings suggest that HFD may induce hyperlipidemia by affecting the gut microbial composition.Changes in the abundance of pro-inflammatory and pathogenic bacteria,and those that influence energy intake and obesity,may be important mediators of this.展开更多
Objective:In this study,we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule(CXG)on cell proliferation,apoptosis,and the cell cycle in vitro.We also used a xenograft tumor ...Objective:In this study,we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule(CXG)on cell proliferation,apoptosis,and the cell cycle in vitro.We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.Methods:The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay.The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry.The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration.The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.Results:CXG suppressed HepG2 cell proliferation in a time-and dose-dependent manner in vitro.Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations(P<.01).Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase.Western blotting results showed that Bax was significantly upregulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration,which increased the Bax/Bcl-2 ratio.PLK1,CDC25 C,CDK1,and Cyclin B1 expression were upregulated.CXG had a good inhibitory effect on graft tumor growth in vivo.Conclusion:CXG has good anti-tumor effects in vitro and in vivo.In vitro,CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest.In vivo,CXG significantly inhibited graft tumor growth.The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression,leading to mitotic catastrophe and apoptosis.展开更多
Objective:To find out host gene expression profiles after malarial infection.Methods:Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed.Results...Objective:To find out host gene expression profiles after malarial infection.Methods:Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed.Results:Up-rcgulation of coagulation-related genes,heal shock proteins,glycolytic enzymes,glucose transporters,and vacuolar H^+-ATPascs was found in acute febrile malaria.In early malaria,prior to detectable parasitemia,CD36 and ICAM1 were up-regulated.During acute malaria,there is correlation between IL-1β and heal shock proteins.CD163,a hemoglobin scavenger receptor,was up-regulated in acute malaria to potentially facilitate free hemoglobin up-takc by leukocytes.In acute malaria,high MafB gene expression was negatively correlated with hemoglobin and platelet counts.Consistent with hemoglobin down-regulation,peripheral red blood cell counts tended to increase during acute malaria.Up-regulations of red blood cell and leucocyte binding mediators like CD36.ICAM1,thrombospondin and thrombomodulin may contribute to the pathogenesis of cerebral malaria.Similarly,up-regulation of correlated glycolytic enzymes,glucose transporter and H^+-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in serious malaria patients.Overall gender effects on gene expression profiles between male and female were not apparent,except for some hemoglobins were significantly downregulated in male versus female,which suggesting males are prone to malaria-related anemia.Conclusions:Leucocyte gene expression profiles can explain the pathogenesis of malarial complication such as fever,metabolic acidosis,hypoglycemia,anemia,and coagulopathy.展开更多
This article details a public acupuncture demonstration that took place on May 9,1972,in San Francisco,California.It was conducted by two traditional Chinese medicine doctors Pien Bae Chi(卞伯岐)and Leung Kok Yuen(梁...This article details a public acupuncture demonstration that took place on May 9,1972,in San Francisco,California.It was conducted by two traditional Chinese medicine doctors Pien Bae Chi(卞伯岐)and Leung Kok Yuen(梁觉玄),and was observed by 500 American medical doctors.This was an important public acupuncture demonstration in the early history of acupunccture in the United States(US).It directly promoted the passage of the first acupuncture bill by California government and had a significant impact on the legalization of acupuncture in California.展开更多
Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu ...Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)were partitioned with petroleum ether,ethyl acetate,n-butanol,and water.The assay forα-glucosidase inhibitory activity revealed strongα-glucosidase inhibitory activity in the ethyl acetate fraction,and the bioactive compounds present in this fraction were identified by the HPLCESI-QTOF-MS/MS method.Results A total of 29 compounds were determined,among the identified bioactive components;these included 12 phenylethanoid glycosides(compounds 5,6,17,20-22,24),7 flavonoids(compounds 10,19,23,25-28),5 phenolic acids(compounds 2-4,7,9),and 5 other compounds.Compounds 2-4,7,9-10,12-13,15,19,and 26,with a potentialα-glucosidase inhibitory activity,have been reported previously.Conclusions Our results show that the methodology used in this study is feasible,credible,and rapid in identifying known compounds and also for characterizing new natural glucosidase inhibitory candidates from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹).展开更多
Objective:To dynamically observe the progression of chronic gastritis to gastric cancer(GC)in diseasetraditional Chinese medicine(TCM)pattern rats to provide data for understanding the disease progression and effectiv...Objective:To dynamically observe the progression of chronic gastritis to gastric cancer(GC)in diseasetraditional Chinese medicine(TCM)pattern rats to provide data for understanding the disease progression and effective approaches for drug screening and mechanism exploration.Methods:Wistar rats were randomly divided into control(n=96,half female and half male)and model(n=336,half female and half male)groups.Model rats received free access to N-methyl-N0-nitro-Nnitrosoguanidine(120 mg/mL),sodium deoxycholate(20 mmol/L),and alcohol(45%),and were subjected to intermittent fasting.Mortality rate,body weight,water consumption,food intake,gastric pathology,blood content analysis,and liver and kidney function of model rats were dynamically monitored over 30 weeks.In the 30th week,pattern characteristics were assessed.Gastric pathology and pattern characteristics were observed for an additional 8 weeks to evaluate stability.Results:The overall mortality of the model group was 34.82%(33.10%for females and 36.55%for males)at 30 weeks post-intervention.Inflammatory cell infiltration,glandular atrophy,atypical hyperplasia,and GC manifested successively in the gastric mucosa of rats.In model rats,N-methyl-N0-nitro-N-nitrosoguanidine intake was lower in males than in females,whereas pathological changes in the gastric mucosa occurred earlier in females than in males.Notably,gastric mucosal lesions were more severe in males than in females.Our modeling methods maintained stable gastric mucosal lesions for at least 8 weeks after final intervention.The pattern characteristics observed in model rats at the 30th and 38th week were consistent with those of spleen deficiency,blood stasis,and yin deficiency pattern.Blood content and indexes of liver and kidney function in the model group were normal.Conclusion:Our findings provide evidence for the pathological stages underscoring the progression of chronic gastritis to GC in disease-TCM pattern rats,which may facilitate development of relevant pharmacotherapies.展开更多
Objective:To investigate whether the specific traditional Chinese medicine(TCM)constitution of individuals can be defined by certain biological indexes instead of answering the questionnaire,and to explore the possibi...Objective:To investigate whether the specific traditional Chinese medicine(TCM)constitution of individuals can be defined by certain biological indexes instead of answering the questionnaire,and to explore the possibility of discriminating nine TCM constitutions from each other simultaneously using biological indexes.Methods:Blood and urine samples from 152 individuals with nine TCM constitutions were collected,and the related biological indexes were analyzed combining ANOVA,multiple comparison,discriminant analysis,and support vector machine.Results:We found that 4 out of 24 blood routine indexes,7 out of 10 urine routine indexes,and 12 out of 32 biochemical indexes showed differences among the constitutions.High-sensitivity C-reactive protein,apolipoprotein A1,and alkaline phosphatase were potential candidates for screening out individuals with unbalanced constitutions.Combining uric acid,high-density lipoprotein,apolipoprotein A1,creatine kinase,total protein,aspartate aminotransferase,total bile acid,dehydrogenase,sodium,and calcium levels had the potential to directly distinguish the nine TCM constitutions from each other.Among these indexes,the highest ratio of discriminant analysis between two constitutions was 95.5%,while the lowest was 66.1%.Conclusion:Our results suggest that some biochemical and urine indexes are related to various TCM constitutions,and thus they have the potential to be used for TCM constitution classification.展开更多
Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57...Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.展开更多
Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD)...Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD) combined with intraperitoneal streptozotocin(STZ) injection. The rats were divided into four groups: the control group(fed with normal feed for1 month), the HFD group(fed with HFD for 1 month), the T2DM group(HFD combined with STZ and blood glucose ≥11.1 m M), and the unformed T2DM model(Un-mod) group(HFD combined with STZ and blood glucose <11.1 m M). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S r RNA gene sequencing. The content of short-chain fatty acids(SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41) and GPR43.Results: At different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased(all P <.05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P <.001).Conclusion: The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.展开更多
Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the...Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing samples.Hence,it is urgent to pursue more efficient approaches for the quality evaluation.Because of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC separation.In current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was achieved.Method validation assays demonstrated the method to be sensitive,precise,accurate,and reproducible.The quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in parallel.Significant differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and G.sinense,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted GAs.More importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.展开更多
Precision medicine has received growing recognition from clinicians, health systems, and the pharmaceutica industry, as well as patients and policymakers, which will leave a major impact on the practice of medicine. I...Precision medicine has received growing recognition from clinicians, health systems, and the pharmaceutica industry, as well as patients and policymakers, which will leave a major impact on the practice of medicine. Interestingly, traditional Chinese medicine （TCM） provides personalized medical treatment based on the theory of TCM characterized by holistic concept and pattem differentiation. This, to some extent, is similar to the personalized medical treatment of precision medicine. In China, TCM as well as Western medicine （WM） plays an important role in healthcare. In this article, the authors summarized the influence of precision medicine on current medical directions, the advantages of TCM in disease treatment, further development of precision medicine and the strategies for integration of TCM and WM under this new treatment approach. In addition, the authors discuss the perspective of precise medical diagnosis and treatment, precise prevention, and the complementary advantages of the integration of TCM and WM. Finally, the authors give their perspectives on the challenges and opportunities presented by precision medicine, in the context of further research toward the integration of TCM and WM.展开更多
OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determ...OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.展开更多
Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the ...Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the potential mechanisms of action of XP.The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks.The study observed the body weight,water intake,bladder and kidney indices(to evaluate their general status),urination behavior pattern(to observe frequency and urgency),and urodynamics(to measure bladder parameters).Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure.Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor,brain-derived neurotrophic factor,and acetylcholine in the urine.The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction,immunohistochemistry,and western blot in vivo/vitro experiments.Result:Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways.XP treatment significantly reduced the bladder index,improved urine behavior and urodynamic parameters,decreased the neurotransmitters in urine,and reduced the thickness of the bladder wall and collagen ratio.These results indicate that XP can alleviate OAB symptoms and improve the bladder structure.In vivo/vitro experiments further demonstrated that XP can inhibit targets,such as muscarinic acetylcholine receptor 2,and participate in cholinergic synapses to further regulate the parasympathetic nervous system.It can also reduce the overexpression of Ca^(2+) caused by agonists,inhibit targets such as transient receptor potential vanilloid type 1,and participate in calcium signaling pathways to maintain Ca^(2+) homeostasis.Conclusion:These results suggest that XP inhibited bladder overactivity by maintaining Ca^(2+) homeostasis and regulating the parasympathetic nervous system.展开更多
Bajiaolian, one of the species in the Mayapple family ( Podophyllum pelatum ), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accumi...Bajiaolian, one of the species in the Mayapple family ( Podophyllum pelatum ), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported.An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg-kg-1 b.w.. The animals were sacrificed 72 h after injection.Neuronal changes were readily observable in animals treated with 10 or 15 mg-kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord.This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.展开更多
Young male rats were orally intubated with podophyllotoxin: Group I, control animals, orally fed with vehicle only; Group Ⅱ, fed with an initial dose of 5 mg.kg-1 b.w., followed by a daily dose of 1.67 mg-kg-1 b.w. f...Young male rats were orally intubated with podophyllotoxin: Group I, control animals, orally fed with vehicle only; Group Ⅱ, fed with an initial dose of 5 mg.kg-1 b.w., followed by a daily dose of 1.67 mg-kg-1 b.w. for 7d. Group III, fed with an initial dose of 15 mg.kg-1 b.w., followed by a daily dose of 5 mg.kg-1 b.w. for 7d. All animals were sacrificed 72 h after the last dosing.Histopathological examination revealed dose-related fatty change of the liver, atrophy andi degenerative changes of the intestinal epithelial linings and testicular seminiferous tubules. Depletion of the pancreatic acinar cell granules was also apparent in the Group III animals. No pathology, however, was observed in the kidneys. The present study demonstrated for the first time degenerative changes in the liver, intestine, testis, and pancreas of animals ingested podophyllotoxin. These pathological changes correlate well with the clinical signs/symptoms of abnormal liver function, abdominal pain and diarrhea, and reduced serum amylase in humans poisonded by podophyllum. Inhibition of protein synthesis and mitosis (disruption of microtubules) are believed to be the underlying mechanisms of these changes observed in the animals intoxicated by. podophyllotoxin.展开更多
Many patients with chronic viral or alcoholic hepatitis,or non-alcoholic steatohepatitis are in the state of chronic liver injury and inflammation and may lead to hepatic fibrosis.The major culprit of liver fibrosis i...Many patients with chronic viral or alcoholic hepatitis,or non-alcoholic steatohepatitis are in the state of chronic liver injury and inflammation and may lead to hepatic fibrosis.The major culprit of liver fibrosis is activation of hepatic stellate cells(HSCs),characterized by transformation from a quiescent phenotype to a proliferative,contractile and secretory phenotype.In a series of study,we use:(1)in vitro cell assays(HSCs)and(2)in vivo rat models of hepatic fibrosis induced by(a)bile duct ligation,and(b)repeated administration of thioacetamide to investigate the anti-hepato-fibrotic effects of potential herbs or their active compounds and illuminate their mechanisms of action.An immortalized cell line of rat HSCs(HSC-T6)is stimulated by transforming growth factor-1(TGF-1),tumor necrosis factor-α(TNF-α)or platelet-derived growth factor(PDGF),and to evaluate the inhibitory effects of herbs on activated HSCs.The possibilities of HSC inhibition via signaling cascades and networks of apoptosis,migration,inflammation,or oxidative stress are examined by standard assays.The in vitro and in vivo anti-fibrotic effects of both salvianolic acids A and B(active hydrophilic compounds from Salvia miltiorrhiza)have been demonstrated in thioacetamide-intoxicated rats,with mechanisms related to reduction of oxidative stress via inhibiting NADPH oxidase in HSCs.Of note is that salvianolic acids A and B exerted both″common″and″different″effects in terms of phosphorylations of various kinases.We also demonstrated that tanshinone ⅡA(C19H18O3,a lipophilic diterpene from S.miltiorrhiza)inhibited lipopolysaccharide-induced HSC chemotaxis and NF-κB activity.The in vivo antihepato-fibrotic effects of a new 3-herb formula including S.miltiorrhiza,Ligusticum chuanxiong and Glycyrrhiza glabra in rats.For studies with anti-inflammatory approach,we demonstrated anti-fibrotic effects of triptolide(from Tripterygium wilfordii)and armepavine(from Nelumbo nucifera),respectively,on hepatic stellate cells and rat models of hepatic fibrosis,with both″common″and″different″anti-inflammatory effects in terms of transcription factors and phosphorylations of mitogen-activated protein(MAP)kinases.We have shown de-activating effects on rat HSCs via mechanisms of cell-migration inhibition(rhubarb,Rheum palmatum extracts)or apoptosis induction(curcumin).Moreover,we observed with bioactivity-directed fractionation approach that Bupleurum scorzonerifolium extracts and kaerophyllin(a lignin thereof)inhibited HSC activation and migration after engulfing hepatocyte apoptotic bodies.The protective effects of kaerophyllin against liver fibrogenesis were demonstrated in rats with upregulation of PPAR-γexpression in the liver.展开更多
AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion....AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion. METHODS: By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.RESULTS: Our Results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death. CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.展开更多
OBJECTIVE:To treat patients with psoriasis vulgaris using Traditional Chinese Medicine(TCM),one must stratify patients into subtypes(known as TCM syndromes or Zheng)and apply appropriate TCM treatments to different su...OBJECTIVE:To treat patients with psoriasis vulgaris using Traditional Chinese Medicine(TCM),one must stratify patients into subtypes(known as TCM syndromes or Zheng)and apply appropriate TCM treatments to different subtypes.However,no unified symptom-based classification scheme of subtypes(Zheng)exists for psoriasis vulgaris.The present paper aims to classify patients with psoriasis vulgaris into different subtypes via the analysis of clinical TCM symptom and sign data.METHODS:A cross-sectional survey was carried out in Beijing from 2005-2008,collecting clinical TCM symptom and sign data from 2764 patients with psoriasis vulgaris.Roughly 108 symptoms and signs were initially analyzed using latent tree analysis,with a selection of the resulting latent variables then used as features to cluster patients into subtypes.RESULTS:The initial latent tree analysis yielded a model with 43 latent variables.The second phase of the analysis divided patients into three subtype groups with clear TCM Zheng connotations:'blood deficiency and wind dryness';'blood heat';and'blood stasis'.CONCLUSIONS:Via two-phase analysis of clinic symptom and sign data,three different Zheng subtypes were identified for psoriasis vulgaris.Statistical characteristics of the three subtypes are presented.This constitutes an evidence-based solution to the syndromedifferentiation problem that exists with psoriasis vulgaris.展开更多
文摘The California Chinese Medicine and Acupuncture Research Association,founded on March 25,1974,is the first Chinese medicine organization registered with the state government in California.It was established after more than a year of arduous preparation and had 15 founding members.Over time,it evolved into the biggest organization of Chinese medicine and acupuncture in California.And in 2015,it became the American Association of Chinese Medicine and Acupuncture with more than 500 members.
基金funded by the National Natural Science Foundation of China(Grant Nos.:82374076,and 82174354)National Key R&D Program of China(Grant No.:2023YFC3504100)+3 种基金Natural Science Foundation of Beijing(Grant No.:7244493)NSFC Cultivating Project of Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences(Grant No.:ZXKT23003)Young Elite Cultivating Project of Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences(Grant No.:ZZ17-YQ-023)Start-up Fund for New Scientific Researchers of China Academy of Chinese Medical Sciences(Grant No.:ZZ16-XRZ071).
文摘Due to the multitudinous structural types of glycosylated components,accurate identification of glycosylation modifications and secondary metabolite structures in herbs remains a challenge for natural drug analysis and new drug discovery[1].To solve this problem,we developed an auxiliary spectral analysis strategy based on Glyco-GNN machine learning techniques(Fig.1).It is named as“Glycomol”,an auxiliary tool for the identification of glycoside molecules.In Glycomol,the structure of glycosylated components was analyzed in terms of parent nucleus,glycan modification sites,and glycan types.Saponins were taken as representative glycosylated components due to their high structural complexity.To estimate the likelihood of results from this modularization strategy,first we extracted the liquid phase and mass spectrum information of 96 structure-known saponins from multi-stage mass spectrometry data.Then,24 standard saponins were applied for analysis and a 95.8%hit rate was achieved.
基金the National Natural Science Foundation of China(81773960 and 81973535)the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2017ZX09301011).
文摘Objective:To determine the effects of a high-fat diet(HFD)on the gut microbiome in rats,to explore the relationship between the intestinal flora and blood lipid profile.Methods:SpragueeDawley rats were fed an HFD for four weeks to induce hyperlipidemia,then 16S rRNA sequencing was used to compare the intestinal flora between hyperlipidemic and control diet-fed rats.Results:The microbiome of rats fed an HFD for four weeks differed from that of control diet-fed rats.Bacterial species that were less abundant were most affected by HFD feeding,among which were many pathogenic species,which became significantly more abundant.Eighteen genera were present in significantly different numbers in hyperlipidemic and control rats,more than half of which have been linked to infection and inflammation,or energy intake and obesity.The results indicated a type of stress response of the flora to a high-fat environment.In addition,the age of the rats tended to influence the gut microbial composition.Conclusion:These findings suggest that HFD may induce hyperlipidemia by affecting the gut microbial composition.Changes in the abundance of pro-inflammatory and pathogenic bacteria,and those that influence energy intake and obesity,may be important mediators of this.
基金the Major Innovative Drug Development Project from Ministry of Science and Technology of the People’s Republic of China(Project No.2017ZX09301011)。
文摘Objective:In this study,we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule(CXG)on cell proliferation,apoptosis,and the cell cycle in vitro.We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.Methods:The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay.The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry.The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration.The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.Results:CXG suppressed HepG2 cell proliferation in a time-and dose-dependent manner in vitro.Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations(P<.01).Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase.Western blotting results showed that Bax was significantly upregulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration,which increased the Bax/Bcl-2 ratio.PLK1,CDC25 C,CDK1,and Cyclin B1 expression were upregulated.CXG had a good inhibitory effect on graft tumor growth in vivo.Conclusion:CXG has good anti-tumor effects in vitro and in vivo.In vitro,CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest.In vivo,CXG significantly inhibited graft tumor growth.The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression,leading to mitotic catastrophe and apoptosis.
文摘Objective:To find out host gene expression profiles after malarial infection.Methods:Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed.Results:Up-rcgulation of coagulation-related genes,heal shock proteins,glycolytic enzymes,glucose transporters,and vacuolar H^+-ATPascs was found in acute febrile malaria.In early malaria,prior to detectable parasitemia,CD36 and ICAM1 were up-regulated.During acute malaria,there is correlation between IL-1β and heal shock proteins.CD163,a hemoglobin scavenger receptor,was up-regulated in acute malaria to potentially facilitate free hemoglobin up-takc by leukocytes.In acute malaria,high MafB gene expression was negatively correlated with hemoglobin and platelet counts.Consistent with hemoglobin down-regulation,peripheral red blood cell counts tended to increase during acute malaria.Up-regulations of red blood cell and leucocyte binding mediators like CD36.ICAM1,thrombospondin and thrombomodulin may contribute to the pathogenesis of cerebral malaria.Similarly,up-regulation of correlated glycolytic enzymes,glucose transporter and H^+-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in serious malaria patients.Overall gender effects on gene expression profiles between male and female were not apparent,except for some hemoglobins were significantly downregulated in male versus female,which suggesting males are prone to malaria-related anemia.Conclusions:Leucocyte gene expression profiles can explain the pathogenesis of malarial complication such as fever,metabolic acidosis,hypoglycemia,anemia,and coagulopathy.
文摘This article details a public acupuncture demonstration that took place on May 9,1972,in San Francisco,California.It was conducted by two traditional Chinese medicine doctors Pien Bae Chi(卞伯岐)and Leung Kok Yuen(梁觉玄),and was observed by 500 American medical doctors.This was an important public acupuncture demonstration in the early history of acupunccture in the United States(US).It directly promoted the passage of the first acupuncture bill by California government and had a significant impact on the legalization of acupuncture in California.
基金the funding support from the China National Natural Science Foundation Funding Project(NO.81503452)Natural Science Foundation of Hunan Province,China(No.14JJ4066)
文摘Objective To identify the compounds withα-glucosidase inhibitory activity from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)using HPLC-ESI-QTOF-MS/MS.Methods The ethanol extracts of Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹)were partitioned with petroleum ether,ethyl acetate,n-butanol,and water.The assay forα-glucosidase inhibitory activity revealed strongα-glucosidase inhibitory activity in the ethyl acetate fraction,and the bioactive compounds present in this fraction were identified by the HPLCESI-QTOF-MS/MS method.Results A total of 29 compounds were determined,among the identified bioactive components;these included 12 phenylethanoid glycosides(compounds 5,6,17,20-22,24),7 flavonoids(compounds 10,19,23,25-28),5 phenolic acids(compounds 2-4,7,9),and 5 other compounds.Compounds 2-4,7,9-10,12-13,15,19,and 26,with a potentialα-glucosidase inhibitory activity,have been reported previously.Conclusions Our results show that the methodology used in this study is feasible,credible,and rapid in identifying known compounds and also for characterizing new natural glucosidase inhibitory candidates from Clerodendrum bungei Steud(Chou Mu Dan,臭牡丹).
基金This study was supported by the Major Innovative Drug Development Project from the Ministry of Science and Technology of the People's Republic of China(2017ZX09301011).
文摘Objective:To dynamically observe the progression of chronic gastritis to gastric cancer(GC)in diseasetraditional Chinese medicine(TCM)pattern rats to provide data for understanding the disease progression and effective approaches for drug screening and mechanism exploration.Methods:Wistar rats were randomly divided into control(n=96,half female and half male)and model(n=336,half female and half male)groups.Model rats received free access to N-methyl-N0-nitro-Nnitrosoguanidine(120 mg/mL),sodium deoxycholate(20 mmol/L),and alcohol(45%),and were subjected to intermittent fasting.Mortality rate,body weight,water consumption,food intake,gastric pathology,blood content analysis,and liver and kidney function of model rats were dynamically monitored over 30 weeks.In the 30th week,pattern characteristics were assessed.Gastric pathology and pattern characteristics were observed for an additional 8 weeks to evaluate stability.Results:The overall mortality of the model group was 34.82%(33.10%for females and 36.55%for males)at 30 weeks post-intervention.Inflammatory cell infiltration,glandular atrophy,atypical hyperplasia,and GC manifested successively in the gastric mucosa of rats.In model rats,N-methyl-N0-nitro-N-nitrosoguanidine intake was lower in males than in females,whereas pathological changes in the gastric mucosa occurred earlier in females than in males.Notably,gastric mucosal lesions were more severe in males than in females.Our modeling methods maintained stable gastric mucosal lesions for at least 8 weeks after final intervention.The pattern characteristics observed in model rats at the 30th and 38th week were consistent with those of spleen deficiency,blood stasis,and yin deficiency pattern.Blood content and indexes of liver and kidney function in the model group were normal.Conclusion:Our findings provide evidence for the pathological stages underscoring the progression of chronic gastritis to GC in disease-TCM pattern rats,which may facilitate development of relevant pharmacotherapies.
基金supported by the National Key Research and Development Project (2019YFC1710104)the National Natural Science Foundation of China (81430099)+1 种基金the International Cooperation and Exchanges (2014DFA32950)the Fundamental Research Funds for the Central Universities (2020-JYB-XJSJJ-026)
文摘Objective:To investigate whether the specific traditional Chinese medicine(TCM)constitution of individuals can be defined by certain biological indexes instead of answering the questionnaire,and to explore the possibility of discriminating nine TCM constitutions from each other simultaneously using biological indexes.Methods:Blood and urine samples from 152 individuals with nine TCM constitutions were collected,and the related biological indexes were analyzed combining ANOVA,multiple comparison,discriminant analysis,and support vector machine.Results:We found that 4 out of 24 blood routine indexes,7 out of 10 urine routine indexes,and 12 out of 32 biochemical indexes showed differences among the constitutions.High-sensitivity C-reactive protein,apolipoprotein A1,and alkaline phosphatase were potential candidates for screening out individuals with unbalanced constitutions.Combining uric acid,high-density lipoprotein,apolipoprotein A1,creatine kinase,total protein,aspartate aminotransferase,total bile acid,dehydrogenase,sodium,and calcium levels had the potential to directly distinguish the nine TCM constitutions from each other.Among these indexes,the highest ratio of discriminant analysis between two constitutions was 95.5%,while the lowest was 66.1%.Conclusion:Our results suggest that some biochemical and urine indexes are related to various TCM constitutions,and thus they have the potential to be used for TCM constitution classification.
基金funded by the Science and Technology Development Fund,Macao,China(007/2020/ALC)Major Basic and Applied Basic Research Projects of Guangdong Province of China(2019B030302005)the National Natural Science Foundation of China(81973535 and 81773960)。
文摘Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.
基金supported by the National Natural Science Foundation of China (81973535 and 81773960)
文摘Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD) combined with intraperitoneal streptozotocin(STZ) injection. The rats were divided into four groups: the control group(fed with normal feed for1 month), the HFD group(fed with HFD for 1 month), the T2DM group(HFD combined with STZ and blood glucose ≥11.1 m M), and the unformed T2DM model(Un-mod) group(HFD combined with STZ and blood glucose <11.1 m M). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S r RNA gene sequencing. The content of short-chain fatty acids(SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41) and GPR43.Results: At different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased(all P <.05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P <.001).Conclusion: The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.
基金financially supported by the National Natural Science Foundation of China(81973444)the Open Research Project Programme of the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao)(SKLQRCM-OP21011).
文摘Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing samples.Hence,it is urgent to pursue more efficient approaches for the quality evaluation.Because of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC separation.In current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was achieved.Method validation assays demonstrated the method to be sensitive,precise,accurate,and reproducible.The quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in parallel.Significant differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and G.sinense,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted GAs.More importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.
文摘Precision medicine has received growing recognition from clinicians, health systems, and the pharmaceutica industry, as well as patients and policymakers, which will leave a major impact on the practice of medicine. Interestingly, traditional Chinese medicine （TCM） provides personalized medical treatment based on the theory of TCM characterized by holistic concept and pattem differentiation. This, to some extent, is similar to the personalized medical treatment of precision medicine. In China, TCM as well as Western medicine （WM） plays an important role in healthcare. In this article, the authors summarized the influence of precision medicine on current medical directions, the advantages of TCM in disease treatment, further development of precision medicine and the strategies for integration of TCM and WM under this new treatment approach. In addition, the authors discuss the perspective of precise medical diagnosis and treatment, precise prevention, and the complementary advantages of the integration of TCM and WM. Finally, the authors give their perspectives on the challenges and opportunities presented by precision medicine, in the context of further research toward the integration of TCM and WM.
基金National Major Scientific and the Technological Special Project:Establishment of a Clinically Oriented Preclinical Research and Development Technology Platform for New Chinese Medicines based on Famous Doctors'Prescriptions(No.2017ZX09301011)"Decoding Traditional Chinese Medicine"Project of Beijing University of Chinese Medicine:New Drugs Research and Development of Chinese Medicine based on Famous Doctors and Famous Prescriptions(No.90010961020020)the Horizontal Project:Preclinical Pharmacology and Pharmacodynamic Research of a New Chinese Medicine—Guilong Granules(No.2016110031007799)。
文摘OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.
基金supported by the Natural Science Foundation in Xinjiang Uygur Autonomous Region(Urumqi,China,2023D01F38).
文摘Objective:To observe the effect of Xipayimaizibizi oral liquid(XP)in an overactive bladder(OAB)experimental rat model and to explore its pharmacological mechanisms.Methods:Network pharmacology was used to explore the potential mechanisms of action of XP.The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks.The study observed the body weight,water intake,bladder and kidney indices(to evaluate their general status),urination behavior pattern(to observe frequency and urgency),and urodynamics(to measure bladder parameters).Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure.Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor,brain-derived neurotrophic factor,and acetylcholine in the urine.The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction,immunohistochemistry,and western blot in vivo/vitro experiments.Result:Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways.XP treatment significantly reduced the bladder index,improved urine behavior and urodynamic parameters,decreased the neurotransmitters in urine,and reduced the thickness of the bladder wall and collagen ratio.These results indicate that XP can alleviate OAB symptoms and improve the bladder structure.In vivo/vitro experiments further demonstrated that XP can inhibit targets,such as muscarinic acetylcholine receptor 2,and participate in cholinergic synapses to further regulate the parasympathetic nervous system.It can also reduce the overexpression of Ca^(2+) caused by agonists,inhibit targets such as transient receptor potential vanilloid type 1,and participate in calcium signaling pathways to maintain Ca^(2+) homeostasis.Conclusion:These results suggest that XP inhibited bladder overactivity by maintaining Ca^(2+) homeostasis and regulating the parasympathetic nervous system.
文摘Bajiaolian, one of the species in the Mayapple family ( Podophyllum pelatum ), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported.An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg-kg-1 b.w.. The animals were sacrificed 72 h after injection.Neuronal changes were readily observable in animals treated with 10 or 15 mg-kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord.This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.
文摘Young male rats were orally intubated with podophyllotoxin: Group I, control animals, orally fed with vehicle only; Group Ⅱ, fed with an initial dose of 5 mg.kg-1 b.w., followed by a daily dose of 1.67 mg-kg-1 b.w. for 7d. Group III, fed with an initial dose of 15 mg.kg-1 b.w., followed by a daily dose of 5 mg.kg-1 b.w. for 7d. All animals were sacrificed 72 h after the last dosing.Histopathological examination revealed dose-related fatty change of the liver, atrophy andi degenerative changes of the intestinal epithelial linings and testicular seminiferous tubules. Depletion of the pancreatic acinar cell granules was also apparent in the Group III animals. No pathology, however, was observed in the kidneys. The present study demonstrated for the first time degenerative changes in the liver, intestine, testis, and pancreas of animals ingested podophyllotoxin. These pathological changes correlate well with the clinical signs/symptoms of abnormal liver function, abdominal pain and diarrhea, and reduced serum amylase in humans poisonded by podophyllum. Inhibition of protein synthesis and mitosis (disruption of microtubules) are believed to be the underlying mechanisms of these changes observed in the animals intoxicated by. podophyllotoxin.
文摘Many patients with chronic viral or alcoholic hepatitis,or non-alcoholic steatohepatitis are in the state of chronic liver injury and inflammation and may lead to hepatic fibrosis.The major culprit of liver fibrosis is activation of hepatic stellate cells(HSCs),characterized by transformation from a quiescent phenotype to a proliferative,contractile and secretory phenotype.In a series of study,we use:(1)in vitro cell assays(HSCs)and(2)in vivo rat models of hepatic fibrosis induced by(a)bile duct ligation,and(b)repeated administration of thioacetamide to investigate the anti-hepato-fibrotic effects of potential herbs or their active compounds and illuminate their mechanisms of action.An immortalized cell line of rat HSCs(HSC-T6)is stimulated by transforming growth factor-1(TGF-1),tumor necrosis factor-α(TNF-α)or platelet-derived growth factor(PDGF),and to evaluate the inhibitory effects of herbs on activated HSCs.The possibilities of HSC inhibition via signaling cascades and networks of apoptosis,migration,inflammation,or oxidative stress are examined by standard assays.The in vitro and in vivo anti-fibrotic effects of both salvianolic acids A and B(active hydrophilic compounds from Salvia miltiorrhiza)have been demonstrated in thioacetamide-intoxicated rats,with mechanisms related to reduction of oxidative stress via inhibiting NADPH oxidase in HSCs.Of note is that salvianolic acids A and B exerted both″common″and″different″effects in terms of phosphorylations of various kinases.We also demonstrated that tanshinone ⅡA(C19H18O3,a lipophilic diterpene from S.miltiorrhiza)inhibited lipopolysaccharide-induced HSC chemotaxis and NF-κB activity.The in vivo antihepato-fibrotic effects of a new 3-herb formula including S.miltiorrhiza,Ligusticum chuanxiong and Glycyrrhiza glabra in rats.For studies with anti-inflammatory approach,we demonstrated anti-fibrotic effects of triptolide(from Tripterygium wilfordii)and armepavine(from Nelumbo nucifera),respectively,on hepatic stellate cells and rat models of hepatic fibrosis,with both″common″and″different″anti-inflammatory effects in terms of transcription factors and phosphorylations of mitogen-activated protein(MAP)kinases.We have shown de-activating effects on rat HSCs via mechanisms of cell-migration inhibition(rhubarb,Rheum palmatum extracts)or apoptosis induction(curcumin).Moreover,we observed with bioactivity-directed fractionation approach that Bupleurum scorzonerifolium extracts and kaerophyllin(a lignin thereof)inhibited HSC activation and migration after engulfing hepatocyte apoptotic bodies.The protective effects of kaerophyllin against liver fibrogenesis were demonstrated in rats with upregulation of PPAR-γexpression in the liver.
基金Supported by National Science Council, No. NSC94-2314-B-077-001, No. NSC101-2320-B-077-003-MY2National Research Institute of Chinese Medicine, No. NRICM95-DHM-04
文摘AIM: To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1 β and interferon-γ-mediated β cell death and abolition of insulin secretion. METHODS: By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.RESULTS: Our Results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death. CONCLUSION: This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.
基金Supported by the Foundation for Establishing Psoriasis Vulgaris Syndrome Diagnostic Criterion by Latent Structure(QN2009-14)by the Scientific Project of Beijing Municipal Science Technology Commission:Study on the Composition Rules of Syndrome Elements on Psoriasis Vulgaris and Standardized Treatments of TCM(D09050703550901)。
文摘OBJECTIVE:To treat patients with psoriasis vulgaris using Traditional Chinese Medicine(TCM),one must stratify patients into subtypes(known as TCM syndromes or Zheng)and apply appropriate TCM treatments to different subtypes.However,no unified symptom-based classification scheme of subtypes(Zheng)exists for psoriasis vulgaris.The present paper aims to classify patients with psoriasis vulgaris into different subtypes via the analysis of clinical TCM symptom and sign data.METHODS:A cross-sectional survey was carried out in Beijing from 2005-2008,collecting clinical TCM symptom and sign data from 2764 patients with psoriasis vulgaris.Roughly 108 symptoms and signs were initially analyzed using latent tree analysis,with a selection of the resulting latent variables then used as features to cluster patients into subtypes.RESULTS:The initial latent tree analysis yielded a model with 43 latent variables.The second phase of the analysis divided patients into three subtype groups with clear TCM Zheng connotations:'blood deficiency and wind dryness';'blood heat';and'blood stasis'.CONCLUSIONS:Via two-phase analysis of clinic symptom and sign data,three different Zheng subtypes were identified for psoriasis vulgaris.Statistical characteristics of the three subtypes are presented.This constitutes an evidence-based solution to the syndromedifferentiation problem that exists with psoriasis vulgaris.
