Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days,...Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.展开更多
A pharmacological network of"component/target/pathway"for Rhizoma coptidis against type 2 diabetes(T2D)was established by network-pharmacology,and the active components of Rhizoma coptidis and its mechanism ...A pharmacological network of"component/target/pathway"for Rhizoma coptidis against type 2 diabetes(T2D)was established by network-pharmacology,and the active components of Rhizoma coptidis and its mechanism were explored.A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME paramcters.The targets of Rhizoma coptidis were predicted by the ligand similarity method.Related pathways were analyzed with databases,and software was used to construct a "component/target path" network.The mechanism was further confirmed by GEO database with R software.A total of 12 active components were screened from Rhizoma coptidis,involving 57 targets including MAPKI,STAT3,INSR,and 38 signaling pathways were associated with T2D.Related signaling pathways included essential pathways for T2D such as insulin resistance,and pathways that had indirect effect on T2D.It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component,multi-target,and multi-pathway forms.展开更多
Objective:To identify the active ingredients,potential targets,and mechanism of Rhizoma coptidis by bioinformatics method,and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments.Methods:The ...Objective:To identify the active ingredients,potential targets,and mechanism of Rhizoma coptidis by bioinformatics method,and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments.Methods:The chemical components of Rhizoma coptidis were collected through database search,and oral bioavailability and drug-likeness were used for preliminary screening.The targets of Rhizoma coptidis and diabetes-related targets were collected by database retrieval and reverse docking techniques,and the biological process of cross-set proteins was analyzed.The inhibitory effects of Rhizoma coptidis onα-glucosidase,α-amylase activity,and advanced glycation end products(AGEs)were determined via in vitro experiments.In addition,the effects of Rhizoma coptidis on preadipocyte differentiation,absorption of glucose by adipocytes,and the level of intracellular triglyceride were investigated using the adipocyte differentiation model.Results:There were 11 potentially active ingredients in Rhizoma coptidis.IL-6,caspase-3,epidermal growth factor receptor(EGFR),MYC,and estrogen receptor 1 were considered as the key genes.The bioinformatics analysis showed that Rhizoma coptidis played an antidiabetic role mainly via biological processes and signaling pathways including hormone receptor activity,glutathione binding,steroid binding,etc.In vitro experiments showed that the extract of Rhizoma coptidis inhibited the activities ofα-glucosidase andα-amylase,and the generation of AGEs;meanwhile,the extract promoted the absorption of glucose by adipocytes.In addition,the extract of Rhizoma coptidis decreased triglyceride level.Conclusions:Our network pharmacology and in vitro experiments demonstrate the anti-diabetic effects and possible underlying mechanisms of Rhizoma coptidis extract.展开更多
[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bact...[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bacteriostasis against known serotype E. coli O2 was conducted using microcheckerboard method.[Result] The MIC of rhizoma coptidis, folium isatidis and flos poprli were 1/8 extracting liquid, 1/8 extracting liquid and 1/2 extracting liquid, respectively. When combined with folium isatidis or flos poprli, the MIC of rhizoma coptidis was 1/8 extracting liq-uid or 1/16 extracting liquid compared with single use. When combined with rhizoma coptidis, the MIC of folium isatidis and flos poprli were 1/8 extracting liquid and 1/16 extracting liquid.[Conclusion] When rhizoma coptidis was combined with folium isatidis or flos poprli, the FIC values were 2 and 0.625, performing independent action and additive effect, respectively.展开更多
Rhizoma Coptidis,a traditional Chinese herbal medicine,has been used for treating diabetes for thousands of years.However,the molecular basis for this action has not been elucidated.In the present study,the effects of...Rhizoma Coptidis,a traditional Chinese herbal medicine,has been used for treating diabetes for thousands of years.However,the molecular basis for this action has not been elucidated.In the present study,the effects of seven main alkaloids of Rhizoma Coptidis on glycometabolism were investigated and the related molecular mechanism of five active compounds on insulin resistant(IR)cell model was explored for the first time.Results showed that berberine,palmatine,epiberberine,columbamine and groenlandicine enhanced glucose consumption in the palmitic acid(PA)-induced IR-HepG2 cells,indicating that these compounds could improve IR.In addition,we found that among these active alkaloids,berberine,columbamine,epiberberine and groenlandicine could inhibit the activation of ERK and p38 pathway,while berberine,columbamine,palmatine and epiberberine could activate AMPK pathway.Moreover,palmatine and columbamine regulated the mRNA expression of GLUT2 to ameliorate IR via activating AMPK and inactivating p38 MAPK signal pathway.To sum up,berberine,columbamine,palmatine,epiberberine and groenlandicine might be the active reagents,which contribute to the glucose lowering effects of Rhizoma Coptidis.展开更多
With the advantages of less toxicity and side effects, traditional Chinese medicine(TCM) is showing a bright future with a good clinical practice. Chinese herbal medicine, which usually contains various active ingredi...With the advantages of less toxicity and side effects, traditional Chinese medicine(TCM) is showing a bright future with a good clinical practice. Chinese herbal medicine, which usually contains various active ingredients, could provide multiple therapeutic effects. Professor Tong Xiaolin has accumulated abundant experience during many years of clinical practice and applies Rhizoma Coptidis(RC) well with the treatment of diabetes and its complications. Rhizoma coptidis is a classical natural herb which is used frequently by professor Tong Xiaolin. In this review, we summarize Tong Xiaolin's clinical experience of applying Rhizoma Coptidis(Huang Lian) in the treatment of disease from two aspects as well as introducing some traditional Chinese medical theory and clinical experience, with a prospect of guiding clinician to use RC more suitably and reasonably.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.展开更多
AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells ...AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations(IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL-1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells.These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.展开更多
OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidne...OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidney nuclear factor-κB(NF-κB) expression in rats with high-fat diet-induced diabetes.METHODS: Diabetes was induced in rats by feeding a high-fat chow combined with intravenous streptozotocin injection. Forty diabetic SpragueDawley rats were randomly assigned to a normal group(NG), model group(MG), irbesartan group(IG), and low-, middle-, and high-dosage FGC groups(LFGC, MFGC, HFGC), with eight rats per group. The IG rats received 31.25 mg·kg^(-1)·d^(-1) irbesartan tablets, whereas those in the LFGC, MFGC,and HFGC were administered 52, 312.5, and 625 mg·kg^(-1)·d^(-1) FGC, respectively. After 12 weeks,bodyweight(BW), left kidney weight(KW), hemoglobin A1c(HbA1c), serum creatinine(Scre), blood urea nitrogen(BUN), and serum MCP-1 and CTGF levels were determined, pathological changes of the kidney were recorded, and kidney NF-κB p65(A) expression was measured.RESULTS: The 24-h urine albumin and levels of HbA1c, Scre, BUN, and serum MCP-1 and CTGF were significantly increased in in the MG compared with the NG, as was the kidney NF-κB(p65) expression(P < 0.05). Furthermore, clear pathological changes in kidney fibrosis were observed in the MG rats. Following irbesartan and FGC administration,the 24-h urine albumin and the levels of HbA1c,Scre, and serum MCP-1 and CTGF were significantly decreased in FCG groups compared with those in the MG, which is in agreement with the change in the kidney NF-κB(p65) expression, whereas the similarly significant decrease only exist in 24-h urine albumin and the levels of serum CTGF after irbesartan administration. Hematoxylin-eosin(HE)staining results indicated that the fibrosis observed in the MG samples was alleviated through FGC treatment.CONCLUSION: FGC may alleviate potential kidney injury by decreasing the serum MCP-1 and CTGF levels and inhibiting NF-k B expression in diabetic nephropathy in rats with high-fat diet-induced diabetes.展开更多
Objective: Sepsis, a systemic response to infection, often leads to end-organ dysfunction. Despite its high rates of mortality and morbidity, its pathophysiology is still poorly understood. Coptidis Rhizoma and its ma...Objective: Sepsis, a systemic response to infection, often leads to end-organ dysfunction. Despite its high rates of mortality and morbidity, its pathophysiology is still poorly understood. Coptidis Rhizoma and its main active alkaloid compound, berberine, have been as anti-bacterial and anti-inflammatory drugs used in clinic. The objective of this study was to gain more insights towards understanding the sepsis associated with drug absorption and disposition and treatments of berberine and Coptidis Rhizoma dynamically.Methods: Pharmacokinetic and metabolomic studies of Coptidis Rhizoma and its main active component berberine have been performed.Results: Cecal ligation and puncture(CLP) induced sepsis showed marked changes of metabolites concerning energy metabolism and amino acids metabolisms, which could be reversed towards the normal state by Coptidis Rhizoma and berberine.Conclusion: Berberine exhibited an equivalent and even better therapeutic effect than Coptidis Rhizoma.展开更多
Objective To establish a new,rapid,and reliable reversed-phase ultra performance liquid chromatography (RP-UPLC)method for the simultaneous determination of six quaternary ammonium alkaloids(QAAs)in Coptidis Rhizoma.M...Objective To establish a new,rapid,and reliable reversed-phase ultra performance liquid chromatography (RP-UPLC)method for the simultaneous determination of six quaternary ammonium alkaloids(QAAs)in Coptidis Rhizoma.Methods The effect of different experimental parameters on the analysis of QAAs by RP-UPLC was evaluated.Results Optimal resolution was achieved with an Acquity UPLC BEH C18 column using a gradient elution profile and a mobile phase consisting of water spiked with 10 mmol/L ammonium bicarbonate(A,pH adjusted to 10.0 by ammonia water)and acetonitrile(B),at a flow rate of 0.30 mL/min and wavelength of 345 nm. The column temperature was set at 30℃.The proposed method was found to be reproducible,precise,and rapid according to the method validation.Conclusion The proposed method,which is compatible with MS analysis and the preparation of QAA,provides some helpful insights into the quality control of Coptidis Rhizoma.展开更多
AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skelet...AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skeletal muscle,the major organ responsible for glucose homeostasis,and activates 5'-AMP-activated protein kinase(AMPK),a signaling intermediary leading to metabolic enhancement of skeletal muscle.METHODS:Isolated rat epitrochlearis and soleus muscles were incubated in a buffer containing a CR water extract(CE),and activation of AMPK and related events were examined.RESULTS:In response to CE treat-ment,phosphorylation of Thr172 at the catalyticαsubunit of AMPK,an essential step for full kinase activation,increased in both mus-cles.Phosphorylation of Ser79 of acetyl CoA carboxylase(ACC),an endogenous substrate of AMPK,increased concomitantly.Analysis of isoform-specific AMPK activity revealed that CE activated both the α1 and α2 isoforms of the catalytic subunit.Importantly,the maximal effect of CE on AMPK phosphorylation was significantly greater than that of berberine(BBR),indicating that the action of CE is not totally ascribed to BBR.CONCLUSION:We propose that CE is an acute activator of AMPK in both fast-and slow-twitch skeletal muscles.展开更多
Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berb...Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.展开更多
文摘Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.
基金This project was supported by National Natural Science Foundation of China(No.31570343).
文摘A pharmacological network of"component/target/pathway"for Rhizoma coptidis against type 2 diabetes(T2D)was established by network-pharmacology,and the active components of Rhizoma coptidis and its mechanism were explored.A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME paramcters.The targets of Rhizoma coptidis were predicted by the ligand similarity method.Related pathways were analyzed with databases,and software was used to construct a "component/target path" network.The mechanism was further confirmed by GEO database with R software.A total of 12 active components were screened from Rhizoma coptidis,involving 57 targets including MAPKI,STAT3,INSR,and 38 signaling pathways were associated with T2D.Related signaling pathways included essential pathways for T2D such as insulin resistance,and pathways that had indirect effect on T2D.It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component,multi-target,and multi-pathway forms.
基金supported by the Sichuan Special Project of TCM Science and Technology Research(No.2016C034)
文摘Objective:To identify the active ingredients,potential targets,and mechanism of Rhizoma coptidis by bioinformatics method,and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments.Methods:The chemical components of Rhizoma coptidis were collected through database search,and oral bioavailability and drug-likeness were used for preliminary screening.The targets of Rhizoma coptidis and diabetes-related targets were collected by database retrieval and reverse docking techniques,and the biological process of cross-set proteins was analyzed.The inhibitory effects of Rhizoma coptidis onα-glucosidase,α-amylase activity,and advanced glycation end products(AGEs)were determined via in vitro experiments.In addition,the effects of Rhizoma coptidis on preadipocyte differentiation,absorption of glucose by adipocytes,and the level of intracellular triglyceride were investigated using the adipocyte differentiation model.Results:There were 11 potentially active ingredients in Rhizoma coptidis.IL-6,caspase-3,epidermal growth factor receptor(EGFR),MYC,and estrogen receptor 1 were considered as the key genes.The bioinformatics analysis showed that Rhizoma coptidis played an antidiabetic role mainly via biological processes and signaling pathways including hormone receptor activity,glutathione binding,steroid binding,etc.In vitro experiments showed that the extract of Rhizoma coptidis inhibited the activities ofα-glucosidase andα-amylase,and the generation of AGEs;meanwhile,the extract promoted the absorption of glucose by adipocytes.In addition,the extract of Rhizoma coptidis decreased triglyceride level.Conclusions:Our network pharmacology and in vitro experiments demonstrate the anti-diabetic effects and possible underlying mechanisms of Rhizoma coptidis extract.
基金Supported by Natural Science Foundation of Shandong Province(ZR2014CQ012)
文摘[Objective] The paper was to explore the combined inhibitory effect of rhizoma coptidis-folium isatidis and rhizoma coptidis-flos poprli against Escherichia coli O2.[Method] Contrast test of single and associated bacteriostasis against known serotype E. coli O2 was conducted using microcheckerboard method.[Result] The MIC of rhizoma coptidis, folium isatidis and flos poprli were 1/8 extracting liquid, 1/8 extracting liquid and 1/2 extracting liquid, respectively. When combined with folium isatidis or flos poprli, the MIC of rhizoma coptidis was 1/8 extracting liq-uid or 1/16 extracting liquid compared with single use. When combined with rhizoma coptidis, the MIC of folium isatidis and flos poprli were 1/8 extracting liquid and 1/16 extracting liquid.[Conclusion] When rhizoma coptidis was combined with folium isatidis or flos poprli, the FIC values were 2 and 0.625, performing independent action and additive effect, respectively.
基金supported by Technology Major Project of China“Key New Drug Creation and Manufacturing Program”(No.2017ZX09301012-001)the National Natural Science Foundation of China(No.20972098,No.81703776 and No.81430095)the National Basic Research Program of China(No.2014CB560706).
文摘Rhizoma Coptidis,a traditional Chinese herbal medicine,has been used for treating diabetes for thousands of years.However,the molecular basis for this action has not been elucidated.In the present study,the effects of seven main alkaloids of Rhizoma Coptidis on glycometabolism were investigated and the related molecular mechanism of five active compounds on insulin resistant(IR)cell model was explored for the first time.Results showed that berberine,palmatine,epiberberine,columbamine and groenlandicine enhanced glucose consumption in the palmitic acid(PA)-induced IR-HepG2 cells,indicating that these compounds could improve IR.In addition,we found that among these active alkaloids,berberine,columbamine,epiberberine and groenlandicine could inhibit the activation of ERK and p38 pathway,while berberine,columbamine,palmatine and epiberberine could activate AMPK pathway.Moreover,palmatine and columbamine regulated the mRNA expression of GLUT2 to ameliorate IR via activating AMPK and inactivating p38 MAPK signal pathway.To sum up,berberine,columbamine,palmatine,epiberberine and groenlandicine might be the active reagents,which contribute to the glucose lowering effects of Rhizoma Coptidis.
文摘With the advantages of less toxicity and side effects, traditional Chinese medicine(TCM) is showing a bright future with a good clinical practice. Chinese herbal medicine, which usually contains various active ingredients, could provide multiple therapeutic effects. Professor Tong Xiaolin has accumulated abundant experience during many years of clinical practice and applies Rhizoma Coptidis(RC) well with the treatment of diabetes and its complications. Rhizoma coptidis is a classical natural herb which is used frequently by professor Tong Xiaolin. In this review, we summarize Tong Xiaolin's clinical experience of applying Rhizoma Coptidis(Huang Lian) in the treatment of disease from two aspects as well as introducing some traditional Chinese medical theory and clinical experience, with a prospect of guiding clinician to use RC more suitably and reasonably.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.
基金supported by the National Natural Science Foundation of China(No.81274078,81322052,81303222)China Postdoctoral Science Foundation(No.2013M532130)
文摘AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations(IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL-1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells.These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.
基金Supported by Beijing Traditional Chinese Medicine Science and Technology Project:Study on the Mechanism of High Dose Huanglian (Rhizoma Coptidis) in Treating Diabetic Nephropathy (No.QN2014-08)。
文摘OBJECTIVE: To investigate the efficacy of the full composition granules of Huanglian(Rhizoma Coptidis)(FGC) on the serum monocyte chemotactic protein-1(MCP-1) and connective tissue growth factor(CTGF) levels and kidney nuclear factor-κB(NF-κB) expression in rats with high-fat diet-induced diabetes.METHODS: Diabetes was induced in rats by feeding a high-fat chow combined with intravenous streptozotocin injection. Forty diabetic SpragueDawley rats were randomly assigned to a normal group(NG), model group(MG), irbesartan group(IG), and low-, middle-, and high-dosage FGC groups(LFGC, MFGC, HFGC), with eight rats per group. The IG rats received 31.25 mg·kg^(-1)·d^(-1) irbesartan tablets, whereas those in the LFGC, MFGC,and HFGC were administered 52, 312.5, and 625 mg·kg^(-1)·d^(-1) FGC, respectively. After 12 weeks,bodyweight(BW), left kidney weight(KW), hemoglobin A1c(HbA1c), serum creatinine(Scre), blood urea nitrogen(BUN), and serum MCP-1 and CTGF levels were determined, pathological changes of the kidney were recorded, and kidney NF-κB p65(A) expression was measured.RESULTS: The 24-h urine albumin and levels of HbA1c, Scre, BUN, and serum MCP-1 and CTGF were significantly increased in in the MG compared with the NG, as was the kidney NF-κB(p65) expression(P < 0.05). Furthermore, clear pathological changes in kidney fibrosis were observed in the MG rats. Following irbesartan and FGC administration,the 24-h urine albumin and the levels of HbA1c,Scre, and serum MCP-1 and CTGF were significantly decreased in FCG groups compared with those in the MG, which is in agreement with the change in the kidney NF-κB(p65) expression, whereas the similarly significant decrease only exist in 24-h urine albumin and the levels of serum CTGF after irbesartan administration. Hematoxylin-eosin(HE)staining results indicated that the fibrosis observed in the MG samples was alleviated through FGC treatment.CONCLUSION: FGC may alleviate potential kidney injury by decreasing the serum MCP-1 and CTGF levels and inhibiting NF-k B expression in diabetic nephropathy in rats with high-fat diet-induced diabetes.
基金funded by the Key Project of the National Natural Science Foundation of China(No.81430092,81773857)the Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R63)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Objective: Sepsis, a systemic response to infection, often leads to end-organ dysfunction. Despite its high rates of mortality and morbidity, its pathophysiology is still poorly understood. Coptidis Rhizoma and its main active alkaloid compound, berberine, have been as anti-bacterial and anti-inflammatory drugs used in clinic. The objective of this study was to gain more insights towards understanding the sepsis associated with drug absorption and disposition and treatments of berberine and Coptidis Rhizoma dynamically.Methods: Pharmacokinetic and metabolomic studies of Coptidis Rhizoma and its main active component berberine have been performed.Results: Cecal ligation and puncture(CLP) induced sepsis showed marked changes of metabolites concerning energy metabolism and amino acids metabolisms, which could be reversed towards the normal state by Coptidis Rhizoma and berberine.Conclusion: Berberine exhibited an equivalent and even better therapeutic effect than Coptidis Rhizoma.
基金National Natural Science Foundation of China(30873385,81173542)the Beijing Natural Science Foundation(7112128)the Open Research Fund of State Key Laboratory Breeding Base of Systematic Research,Development and Utilization of Chinese Medicinal Resources
文摘Objective To establish a new,rapid,and reliable reversed-phase ultra performance liquid chromatography (RP-UPLC)method for the simultaneous determination of six quaternary ammonium alkaloids(QAAs)in Coptidis Rhizoma.Methods The effect of different experimental parameters on the analysis of QAAs by RP-UPLC was evaluated.Results Optimal resolution was achieved with an Acquity UPLC BEH C18 column using a gradient elution profile and a mobile phase consisting of water spiked with 10 mmol/L ammonium bicarbonate(A,pH adjusted to 10.0 by ammonia water)and acetonitrile(B),at a flow rate of 0.30 mL/min and wavelength of 345 nm. The column temperature was set at 30℃.The proposed method was found to be reproducible,precise,and rapid according to the method validation.Conclusion The proposed method,which is compatible with MS analysis and the preparation of QAA,provides some helpful insights into the quality control of Coptidis Rhizoma.
基金supported by the research grants from the Japan Society for the Promotion of Science (No.20500576)Japan Vascular Disease Research Foundation
文摘AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skeletal muscle,the major organ responsible for glucose homeostasis,and activates 5'-AMP-activated protein kinase(AMPK),a signaling intermediary leading to metabolic enhancement of skeletal muscle.METHODS:Isolated rat epitrochlearis and soleus muscles were incubated in a buffer containing a CR water extract(CE),and activation of AMPK and related events were examined.RESULTS:In response to CE treat-ment,phosphorylation of Thr172 at the catalyticαsubunit of AMPK,an essential step for full kinase activation,increased in both mus-cles.Phosphorylation of Ser79 of acetyl CoA carboxylase(ACC),an endogenous substrate of AMPK,increased concomitantly.Analysis of isoform-specific AMPK activity revealed that CE activated both the α1 and α2 isoforms of the catalytic subunit.Importantly,the maximal effect of CE on AMPK phosphorylation was significantly greater than that of berberine(BBR),indicating that the action of CE is not totally ascribed to BBR.CONCLUSION:We propose that CE is an acute activator of AMPK in both fast-and slow-twitch skeletal muscles.
基金supported by the National Natural Science Foundation of China(grant numbers 81874348,81303239)the Natural Science Foundation of Anhui Province(grant numbers 1908085J29)+3 种基金the Key Research and Development Plan of Anhui Province(grant number 201904b11020023)the Open Project of State Key Laboratory of Natural Medicines(grant number SKLNMKF202007)the Provincial Foundation for Excellent Young Talents of Colleges and Universities of Anhui Province(grant number gxyqZD2018052)the Anhui Provincial Department of Education(grant number KJ2018A0282)。
文摘Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.
