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1.
Article in Chinese | WPRIM | ID: wpr-928137

ABSTRACT

Toxicity-attenuating compatibility is an effective measure to ensure the safety of Chinese medicine. Involving the origin, processing method, compatibility mode, and dosage, it faces multiple challenges, such as the uncertainty of toxic substances, toxicity latency, indefinite safe dose, complex toxicity-efficacy relationship, and individual difference. As a result, research on clinical safety of Chinese medicine is limited by the consistency at "molecular-cellular-organ-overall" levels, unclear interaction of multiple medicinals and multiple substances, the "toxicity-efficacy-compatibility-syndrome" correlation, and the "dosage-time-toxicity-efficacy" conversion law. Therefore, following the principle of "starting from the clinical practice, verifying via the theoretical basis, and finally applying in clinical practice", we verified the toxicity at "molecular-cellular-organ-overall" levels, revealed the interaction of multiple medicinals and substances, collected evidence at multiple levels, clarified the "dosage-time-toxicity-efficacy" relationship, and tested the consistency between basic and clinical biomarkers. On this basis, we studied the toxicity-alleviating and efficacy-enhancing(preserving) compatibility characteristics, the fate of one medicinal and multiple medicinals in vivo, the molecular mechanism of toxicity, the "dosage-time-toxicity-efficacy" conversion law, and the clinical characteristics of toxic traditional Chinese medicine based on disease and syndrome. The three mechanisms of toxicity-attenuating compatibility reflect the seven-reaction theory in Chinese medicine compatibility. Finally, the strategies for safe use of Chinese medicine were proposed.


Subject(s)
Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , Research Design
2.
Article in Chinese | WPRIM | ID: wpr-879082

ABSTRACT

Since "the implementation of good clinical practice"(GCP), especially after 2015, the overall quality of new drug cli-nical trials in China has made significant progress, but compared with developed countries, there are still some obvious quality problems in clinical trials in China. Clinical trials of new drugs of traditional Chinese medicine are an important part of clinical trials of new drugs in China. In addition to some common problems in all clinical trials, there are also some special quality problems. In terms of security data, such as the collection of human safety data is not standardized, the management and judgment of unexpected serious adverse reactions(SUSAR) were not professional and timely, the relationship between adverse events and trial drug was not fully judged by investigator, In terms of effective data, such as primary efficacy outcome of the scale cannot be traced, TCM syndrome data cannot meet the requirements of "source data" in the revised GCP and the quality of traditional Chinese medicine placebo is not high, in terms of overall quality system construction, the sponsors and research institutions have not established a quality assurance system that conforms to the characteristics of new drug research of traditional Chinese medicine, etc. The quality of clinical trials of new drugs of traditional Chinese medicine is based on the current GCP and ICH-GCP in China, we should also consider the characteristics of clinical trials of new traditional Chinese medicine drugs, and formulate targeted quality control measures according to the characteristics of these new drugs of traditional Chinese medicine, to improve the overall quality of clinical trials of new drugs of traditional Chinese medicine in China, which has important strategic significance for promoting the research and development of new drugs of traditional Chinese medicine in China.


Subject(s)
China , Clinical Trials as Topic , Consensus , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Quality Control
3.
Article in Chinese | WPRIM | ID: wpr-879081

ABSTRACT

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.


Subject(s)
Biomedical Research , Clinical Trials as Topic , Consensus , Drugs, Chinese Herbal , Ethical Review , Humans , Medicine, Chinese Traditional , Multicenter Studies as Topic , Pharmaceutical Preparations
4.
Article in Chinese | WPRIM | ID: wpr-879078

ABSTRACT

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.


Subject(s)
Data Collection , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Prescriptions , Quality Control
5.
Article in Chinese | WPRIM | ID: wpr-921721

ABSTRACT

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.


Subject(s)
Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional , Prescriptions , Reproducibility of Results , Research
6.
Article in Chinese | WPRIM | ID: wpr-824977

ABSTRACT

Objective: To observe the therapeutic efficacy of sinew-bone balancing manipulation plus exercise therapy in treating postures of primary school students with upper crossed syndrome (UCS).Methods: Sixty pupils with UCS were divided into an exercise group and a combination group using the random number table method, with 30 cases in each group. The combination group received treatments of sinew-bone balancing manipulation plus exercise therapy, while the exercise group received exercise therapy alone. The two groups received interventions once every other day, for a total of 1 month. The sagittal static posture assessment total score, forward head angle (FHA) and forward shoulder angle (FSA) were compared before and after treatment; the sagittal static assessment total score, FHA and FSA were compared between the exercise group and the combination group. Results: Before treatment, there were no significant differences comparing the sagittal static posture assessment total score, FHA and FSA between the two groups (all P>0.05); after treatment, the sagittal static posture assessment total score, FHA and FSA decreased in the two groups, with intra-group statistical significance (all P<0.01), and were lower in the combination group than in the exercise group, with inter-group statistical significance (all P<0.01). Conclusion: Sinew-bone balancing manipulation plus exercise therapy can notably improve the FHA and FSA and reduce the sagittal static posture total score in pupils with UCS, so as to correct the bad postures and adjust UCS physique. It can produce more significant efficacy compared with exercise therapy alone.

7.
Article in English | WPRIM | ID: wpr-691399

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.</p><p><b>METHODS</b>A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.</p><p><b>RESULTS</b>Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).</p><p><b>CONCLUSION</b>SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.</p>


Subject(s)
Animals , Disease Models, Animal , Drugs, Chinese Herbal , Therapeutic Uses , HMGB1 Protein , Metabolism , Liver , Metabolism , Pathology , Liver Cirrhosis , Drug Therapy , Metabolism , Pathology , Male , Rats , Rats, Sprague-Dawley , Signal Transduction , Smad Proteins , Metabolism
8.
Article in Chinese | WPRIM | ID: wpr-230135

ABSTRACT

As a representative variety of hypertoxic herbs, aconite has a very high medicinal value but certain security risks. With the advance of urbanization and industrial transfer and upgrading, traditional geo-authentic regions and emerging regions have gradually coexisted. However, there are significant differences in the geographical distribution, ecological environment and growing cycle in these areas, which may cause intraspecific variations in chemical components, and then affect herb quality and clinical efficacy. Furthermore, there was still lack of in-depth study on characteristic constituents of aconite genuineness. In this paper, an UPLC-Q-TOF-MS was used to investigate the chemical ingredients in Jiangyou aconite, Hanzhong aconite, Butuo aconite and Weishan aconite. The results suggested that using unsupervised PCA method, Jiangyou aconite was similar with Hanzhong aconite in chemical ingredients, but significantly different from ones in emerging regions. Using PLS-DA method, seven characteristic constituents were identified, in which Butuo aconite and Weishan aconite had higher contents of mesaconitine and fuziline, while Jiangyou aconite and Hanzhong aconite had higher contents of hypaconitine, neoline, carmichaeline, and songorine. Based on basic toxicity of each ingredient, we can find that hypaconitine and mesaconitine were the key toxicity factors to distinguish Jiangyou aconite, Butuo aconite, and Weishan aconite. The toxicity of geo-authentic Jiangyou aconite was lower than that of Butuo aconite and Weishan aconite. The lower toxicity in geo-authentic Jiangyou aconite was beneficial for ensuring clinical drug safety, which may be one of the important reasons for the formation of genuine aconite. These results provide new reference data to reveal the formation mechanism of genuine aconite from the perspective of plant secondary metabolite diversity.

9.
Article in English | WPRIM | ID: wpr-301080

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction (, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus (HBV-ACLF) with cold pattern in Chinese medicine (CM).</p><p><b>METHODS</b>This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine (WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM (integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease (MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported.</p><p><b>RESULTS</b>The mortality was decreased 14.28% in the integrative treatment group compared with WM group (χ(2) =6.156, P=0.013). The integrative treatment was found to signifificantly improve the MELD score (t=2.353, P=0.020). There were statistically signifificant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups (P<0.05 or P<0.01). The complications of ascites (χ(2)=9.033, P=0.003) and spontaneous bacteria peritonitis (χ(2)=4.194, P=0.041) were improved signifificantly in the integrative treatment group. No serious adverse event was reported.</p><p><b>CONCLUSIONS</b>The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy. (Trial registration No. ChiCTR-TRC-10000766).</p>


Subject(s)
Acute-On-Chronic Liver Failure , Drug Therapy , Mortality , Virology , Adult , Ascites , Demography , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Electrolytes , Female , Hepatitis B , Drug Therapy , Mortality , Hepatitis B virus , Physiology , Humans , Integrative Medicine , Liver , Pathology , Virology , Liver Function Tests , Male , Peritonitis , Time Factors , Treatment Outcome
10.
Article in Chinese | WPRIM | ID: wpr-838800

ABSTRACT

Objective Todesign a novel impedimetric immunosensor basedon AgI mimic enzyme nanomaterial for detecting carcinoembryonic antigen (CEA) in serum with high sensitivity. Methods A novil chitosan modified AgI (CS-AgI) nanomaterial was synthesized and was characterized by transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR). Then by utilizing CS-AgI labeled CEA antibody as tags, we prepared a novel impedimetric immunosensor on the gold electrode using the sandwich-type immunoassay. The electrochemical propertiesof the prepared impedimetric immunosensor were observed by electrochemical workstation and the concentration of CEA in sample was quantitatively analyzed. Results The synthesized CS-AgI nanoparticles were spherical in shape, with the particle size being 100 nm; the particles were employed to construct immunosensor as signal markers. The immunosensor had an excellent electrochemical performance in detection of CEA under PBS base solution of pH = 7, and its AC impedance response increased with the increase of the logarithm of CEA concentration, exhibiting a good linear relationship in the range of 0. 1ng/mL to 80ng/mL (r = 0.996), with a detection limkof 0. 05 ng/mL. Conclusion Based on AgI mimic enzyme nanomaterial, the impedance immunosensor prepared in this study shows a high sensitivity in detecting CEA; meanwhile, t has acceptable selectivity, repeatability and stability, providing an experimental evidence for early diagnosis and treatment of cancer.

11.
Article in English | WPRIM | ID: wpr-812555

ABSTRACT

Anti-influenza Chinese herbal medicines (anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most of them could not be compared using the standard evaluation methods for antiviral activity. This situation poses an obstacle to a wide application of anti-flu CHMs. Thus, it was necessary to develop an evaluation method to estimate antiviral activities of anti-flu CHMs. In the present study, we searched for anti-flu CHMs, based on clinic usage, to select study objects from commonly-used patented anti-flu Chinese medicines. Then, a neuraminidase-based bioassay, optimized and verified by HPLC method by our research group, was adopted to detect antiviral activities of selected 26 anti-flu CHMs. Finally, eight of these herbs, including Coptidis Rhizoma, Isatidis Folium, Lonicerae Flos, Scutellaria Radix, Cyrtomium Rhizome, Houttuynia Cordata, Gardeniae Fructus, and Chrysanthemi Indici Flos, were shown to have strong antiviral activities with half maximal inhibitory concentration (IC) values being 2.02 to 6.78 mg·mL (expressed as raw materials). In contrast, the IC value of positive control peramivir was 0.38 mg·mL. Considering the extract yields of CHMs, the active component in these herbs may have a stronger antiviral activity than peramivir, suggesting that these herbs could be further researched for active compounds. Moreover, the proposed neuraminidase-based bioassay was high-throughput and simple and could be used for evaluation and screening of anti-flu CHMs as well as for their quality control.


Subject(s)
Antiviral Agents , Chemistry , Pharmacology , Drug Evaluation, Preclinical , Drugs, Chinese Herbal , Chemistry , Pharmacology , Enzyme Inhibitors , Chemistry , Pharmacology , Humans , Influenza, Human , Drug Therapy , Virology , Neuraminidase , Metabolism , Orthomyxoviridae , Physiology , Viral Proteins , Metabolism
12.
Acta Pharmaceutica Sinica ; (12): 28-33, 2015.
Article in Chinese | WPRIM | ID: wpr-251822

ABSTRACT

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.


Subject(s)
Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Chemical and Drug Induced Liver Injury , Pathology , Hepatocytes , Pathology , Lipopolysaccharides , Polygonum , Toxicity , Rats , Rats, Sprague-Dawley
13.
Gut and Liver ; : 525-533, 2015.
Article in English | WPRIM | ID: wpr-149096

ABSTRACT

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.


Subject(s)
Anti-Bacterial Agents/adverse effects , Bilirubin/blood , Child , Child, Preschool , China , Chemical and Drug Induced Liver Injury/blood , Drugs, Chinese Herbal/adverse effects , Female , Humans , Liver/pathology , Male , Prothrombin Time , Respiratory Tract Infections/complications , Retrospective Studies
14.
Acta Pharmaceutica Sinica ; (12): 973-979, 2015.
Article in Chinese | WPRIM | ID: wpr-257039

ABSTRACT

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.


Subject(s)
Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Bile Acids and Salts , Metabolism , Bilirubin , Blood , Chemical and Drug Induced Liver Injury , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Fallopia multiflora , Chemistry , HMGB1 Protein , Metabolism , Hepatocytes , Interleukin-1beta , Metabolism , Liver , Pathology , Plant Extracts , Pharmacology , Rats , Tumor Necrosis Factor-alpha , Metabolism
15.
Article in Chinese | WPRIM | ID: wpr-330182

ABSTRACT

To investigate the difference of liver injury in rats gavaged with crude and processed Polygoni Multiflori Radix. The 75% ethanol extract of crude and processed Polygoni Multiflori Radix (50 g · kg(-1) crude medicine weight/body weight) were continuous oral administered to rats for 6 weeks. Serum biochemical indicators were dynamically detected, the change of liver histopathology was assessed 6 weeks later. Principal component analysis (PCA) was adopted to screen sensitive indicator of the liver damage induced by polygoni multiflori radix. Biochemical tests showed that the crude Polygoni Multiflori Radix group had significant increase of serum ALT, AST, ALP, DBIL and TBIL (P < 0.01 or P < 0.05) and significant decreases of serum IBIL and TBA (P < 0.01 or P < 0.05), while the processed Polygoni Multiflori Radix group showed no obvious changes, compared to the untreated normal group. Histopathologic analysis revealed that crude Polygoni Multiflori Radix group exhibited significant inflammatory cells infiltration in portal area around the blood vessels, tissue destruction and local necrosis of liver cells. There were not obvious pathological changes in processed Polygoni Multiflori Radix group. The results demonstrated that the injury effect of processed Polygoni Multiflori Radix on liver injury of rats was significantly lower than that of unprocessed, and that processing can effectively reduce the hepatotoxicity of Polygoni Multiflori Radix. Traditional transaminase liver function indicators were not sensitive for crude Polygoni Multiflori Radix induced liver damage. The serum content of DBIL and TBIL can reflect the liver damage induced by crude Polygoni Multiflori Radix early and can be sensitive indicators for clinical monitoring the usage of it.


Subject(s)
Animals , Chemical and Drug Induced Liver Injury , Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Toxicity , Female , Liver , Wounds and Injuries , Male , Plant Roots , Chemistry , Toxicity , Polygonum , Chemistry , Toxicity , Rats
16.
Article in Chinese | WPRIM | ID: wpr-337936

ABSTRACT

Toxicity of different processed was evaluated Polygoni Multiflori Radix by determining the hepatotoxic potency for selecting processing technology. Process Polygoni Multiflori Radix using high pressure steamed, Black Bean high pressure steamed, atmospheric steamed for different time. Using normal human hepatocytes (L02) as evaluation model, hepatotoxic potency as index to evaluate hepatotoxic potency of different processed Polygoni Multiflori Radix. Analysis chemical composition of some processed products by UPLC-MS. Hepatotoxic bioassay method cloud evaluate the toxicity of different Polygoni Multiflori Radix samples. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix, high pressure steamed three hours attenuated was better. Different processing methods have different effects on chemical constituents of Polygoni Multiflori Radix. Comparing with crude sample, the contents of gallic acid, 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside, emodin-8-O-beta glucoside and emodin were decreased in processed products with 3 kinds of different methods. The change trend of 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside content was similar with hepatotoxic potency. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix. Processing methods and time attenuated obvious impact on toxicity. Recommended further research on the attehuated standard control of Polygoni Multiflori Radix concocted.


Subject(s)
Biological Assay , Cell Line , Chemistry, Pharmaceutical , Methods , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Toxicity , Fallopia multiflora , Chemistry , Toxicity , Hepatocytes , Humans , Plant Roots , Chemistry , Toxicity
17.
Article in Chinese | WPRIM | ID: wpr-327867

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the dosage-efficacy/toxicity relationship of prepared rhubarb, in order to explore the bidirectional effects in hepatoprotection and hepatotoxicity of prepared rhubarb and the objective authenticity for attenuating toxicity by processing.</p><p><b>METHOD</b>Normal and pathological animals were adopted simultaneous to investigate the effect of total extracts from prepared rhubarb within a high dose range (2.0, 5.4, 14.7, 40.0 g x kg(-1) x d(-1)) on normal state, biochemical index and histopathology of experimental animals. The factor analytic approach was used to analyze the dosage-efficacy/toxicity relationship of prepared rhubarb.</p><p><b>RESULT</b>The factor analytic approach was used to extract two common factors from the nine biochemical indexes. The firs common factor was mainly dominated by HA, LN and TGF-β1, and could be explained as fibrotic factors. The second common factor was mainly dominated by ALT, AST and ALP, and could be explained as cellular factor. The results of the factor analysis suggested that prepared rhubarb showed significant bidirectional effects in hepatoprotection and hepatotoxicity, which could protect liver in CC14 injured chronic hepatic injury, but had a certain hepatotoxic effect to normal animals. The pathological examination showed consistent results with the factor analysis. Under comparable dosages, prepared rhubarb showed a stronger liver protecting effect than crude rhubarb, with a lower toxicity.</p><p><b>CONCLUSION</b>Although prepared rhubarb has a certain hepatotoxic effect to normal animals, it has also a significant therapeutic effect to animals with liver injury. The results proved the symptom-based prescription theory and the scientificity of the symptom-based medication. The symptom-based prescription theory is important to correctly realize the dosage-efficacy/toxicity relationship of traditional Chinese medicines and guide the symptom-based medication.</p>


Subject(s)
Animals , Dose-Response Relationship, Drug , Drug Prescriptions , Drugs, Chinese Herbal , Pharmacology , Toxicity , Female , Fibrosis , Liver , Metabolism , Pathology , Male , Rats , Rats, Sprague-Dawley , Rheum , Chemistry , Toxicity Tests
18.
Article in Chinese | WPRIM | ID: wpr-337257

ABSTRACT

<p><b>OBJECTIVE</b>To observe improved effects of Jingjin acupuncture on fine activity of hemiplegic hand in recovery period of stroke.</p><p><b>METHODS</b>Fifty cases were randomly divided into an observation group and a control group, 25 cases in each one. Regular western medicine treatment, rehabilitation training and regular acupuncture (in which Shuigou (GV 26), Baihui (GV 20), Neiguan (PC 6), etc. were selected) were applied in both groups. Additionally, muscles in palm side of affected hand, dorsal metacarpophalangeal joints and proximal interphalangeal joints were treated with acupuncture in the observation group, once every other day and electroacupuncture was applied when arrival of qi was acquired. Baxie (EX-UE 9) in the affected hand were needled in the control group, and electroacupuncture was added when arrival of qi was acquired. Ten days of treatment was considered a treatment course, and after two courses Lindmark score, Brunnstrom movement function grade, joint range of hand and Barthel index (BI) were observed in two groups.</p><p><b>RESULTS</b>Compared before the treatment, the Lindmark score in two groups were both improved after the treatment (both P < 0.01). Compared with the control group, the motor coordination ability, sensory function and total score of Lindmark in observation group were obviously improved (differences before and after treatment: 8.24 +/- 3.07 vs 6.84 +/- 2.43, 3.52 +/- 2.33 vs 2.16 +/- 2.12, 11.76 +/- 3.55 vs 9.00 +/- 3.62, all P < 0.05). The Brunnstrom movement function grade was significantly improved in both groups after treatment (both P < 0.01), which was more obvious in the observation group (P < 0.05). The joint range of hemiplegic hand was improved in both groups after treatment (both P < 0.01), which was more obvious in the observation group [differences before and after treatment: (25.35 +/- 10.91) degrees vs (18.65 +/- 7.86) degrees, p < 0.05]. The score of BI was also significantly improved after treatment in two groups (both P < 0.01).</p><p><b>CONCLUSION</b>The Jingjin acupuncture could effectively improve fine activity of hemiplegic hand in recovery period of stroke prove daily life ability.</p>


Subject(s)
Acupuncture Therapy , Aged , Female , Hand , Hemiplegia , Therapeutics , Humans , Male , Middle Aged , Movement , Recovery of Function , Stroke
19.
Article in Chinese | WPRIM | ID: wpr-294411

ABSTRACT

<p><b>OBJECTIVE</b>To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.</p><p><b>METHODS</b>One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.</p><p><b>RESULTS</b>Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.</p><p><b>CONCLUSIONS</b>Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.</p>


Subject(s)
Animals , Anthraquinones , Pharmacology , Carbon Tetrachloride , Toxicity , Chemical and Drug Induced Liver Injury , Drug Therapy , Pathology , Dose-Response Relationship, Drug , Female , Liver , Male , Rats , Rats, Sprague-Dawley , Rheum , Chemistry , Tannins , Pharmacology
20.
Acta Pharmaceutica Sinica ; (12): 286-290, 2013.
Article in Chinese | WPRIM | ID: wpr-235670

ABSTRACT

In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.


Subject(s)
Aconitine , Toxicity , Aconitum , Chemistry , Animals , Chromatography, High Pressure Liquid , Cluster Analysis , Drugs, Chinese Herbal , Toxicity , Male , Rats , Rats, Sprague-Dawley , Technology, Pharmaceutical , Methods
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