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OBJECTIVE@#To investigate the effect of Chaihu Guizhi Decoction (CHGZD) combined with capecitabine on growth and apoptosis of subcutaneous triple-negative breast cancer xenografts in nude mice and explore the possible mechanism.@*METHODS@#Nude mouse models bearing subcutaneous triple-negative breast cancer xenografts were randomized into 6 groups (n=10) for treatment with distilled water (model group), low (10.62 g/kg), medium (21.23 g/kg) and high (42.46 g/kg) doses of CHGZD, capecitabine (0.2 mg/kg), or the combination of CHGZD (42.46 g/kg) and capecitabine (0.2 mg/k) once daily for 21 consecutive days. The general condition of mice was observed, and after 21-day treatments, the tumors were dissected for measurement of tumor volume and weight and histopathological examination with HE staining. Serum IL-6 levels of the mice were determined with enzyme-linked immunosorbent assay (ELISA), and the expression levels of IL-6, STAT3, p-STAT3, Bax, Bcl-2 and cyclin D1 in the tumor tissues were detected using real-time PCR and Western blotting.@*RESULTS@#Compared with those in the model group, the tumor-bearing mice receiving treatments with CHGZD showed significantly increased food intake with good general condition, sensitive responses, increased body weight, and lower tumor mass (P < 0.01). Compared with capecitabine treatment alone, treatment with CHGZD alone at the medium and high doses and the combined treatment all resulted in significantly higher tumor inhibition rates (P < 0.01), induced obvious tumor tissue degeneration and reduced the tumor cell density. Treatments with CHGZD, both alone and in combination with capecitabine, significantly decreased serum IL-6 level, lowered the mRNA expression levels of IL-6 and STAT3, the protein expressions of IL-6, STAT3 and P-STAT3 (P < 0.05), and the mRNA and protein expressions of Bcl-2 and cyclin D1 (P < 0.05), and increased the mRNA and protein expressions of Bax in the tumor tissues (P < 0.05).@*CONCLUSION@#CHGZD combined with capecitabine can significantly inhibit tumor growth in nude mice bearing triple-negative breast cancer xenografts, the mechanism of which may involve the inhibition of IL-6/STAT3 signaling pathway and regulation of Bax, Bcl-2 and cyclin D1 expressions to suppress tumor cell proliferation and differentiation and induce cell apoptosis.
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Animals , Humans , Mice , Capecitabine/pharmacology , Cyclin D1/metabolism , Drugs, Chinese Herbal , Heterografts , Interleukin-6/metabolism , Mice, Nude , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , Triple Negative Breast Neoplasms/drug therapy , bcl-2-Associated X Protein/metabolismABSTRACT
OBJECTIVE：To study the compositi on of the volatile oil from Compound chaihu guizhi decoction ，and to evaluate its in vitro anti-proliferative activity on human lung adenocarcinoma A 549 cells. METHODS ：The volatile oil from Chaihu guizhi decoction was extracted according to the steam distillation method of general rules 2004 in the 2015 edition of Chinese Pharmacopoeia（part Ⅳ）. The volatile oil components were analyzed by GC-MS combined with Kováts index ，and the relative content of each component was calculated by peak area normalization method. Using different concentrations of cisplatin （4，8， 16，32，64 mg/L）as positive control ，MTT assay was used to detect the inhibitory effects of different concentrations of volatile oil from Chaihu guizhi decoction （25，50，100，200，400 mg/L）on in vitro proliferation of A 549 cell after 48 h of treatment. Negative control group （with cells but without drugs ）was set up. RESULTS ：A total of 71 chemical components were isolated from the volatile oil ，among which there were 59 compounds identified ，sum of peak areas accounting for 84.99％ of the total peak area. The compounds with relatively high content included ar-curcumene （17.65％），β-bisabolene（9.57％），β-ocimene（7.05％）， α-curcumene（5.35％），2，5-dimethylbenzaldehyde（4.24％），linalyl isobutyrate （2.70％），α-cedrene（2.48％），δ-cadinene （2.07％）. Compared with negative control group ，the proliferation rate of cells were decreased significantly in 4-64 mg/L cisplatin groups and 25-400 mg/L volatile oil from Chaihu guizhi decoction groups （P＜0.05）. IC 50 of cisplatin and volatile oil from Chaihu guizhi decoction to in vitro proliferation of A 549 cells were 10.150 and 73.526 mg/L. CONCLUSIONS ：The volatile oil from Chaihu guizhi decoction mainly includes ar-curcumene ，β-bisabolene，β-ocimene，α-curcumene，which shows certain inhibitory effect on in vitro proliferation of A 549 cells.
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Objective::To explore the regulatory effect of Longmu Guizhi decoction and its decomposed formula on the hypothalamic-pituitary-adrenal axis of spontsneously hyoertensive rats (SHR) with attention deficit hyperactivity disorder (ADHD), so as to explain the scientific connotation of compound compatibility. Method::Young male SHR rats were randomly divided into saline control group, methylphenidate hydrochloride group(2 mg·kg-1), Longmu Guizhi decoction group(30 g·kg-1), Guizhi+ Longgu Muli decoction group(21 g·kg-1), Ganmai Dazaotang group(9.24 g·kg-1) and Polygalae Radix-Acori Tatarinowii Rhizome group(4.62 g·kg-1). The corresponding drugs were intragastrically administered for 14 days. Serum adrenocorticotropic hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by enzyme-linked immunosorbent assay(ELISA), and mRNA expressions of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), CRH in hypothalamus and GR, MR in hippocampus were detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) method. Result::Serum CORT, ACTH and CRH, GR and CRH mRNA expressions of hypothalamus, GR and MR mRNA expressions of hippocampus in methylphenidate hydrochloride group and Longmu Guizhi decoction group were significantly higher than those of saline control group (P<0.05, P<0.01). MR mRNA expression of hypothalamus in Longmu Guizhi decoction group was significantly higher than that in the saline control group (P<0.05, P<0.01), and GR expression in hippocampus was significantly higher than that in the methylphenidate hydrochloride group (P<0.01). The dissection study showed that the levels of serum ACTH and CRH, MR mRNA, GR and CRH mRNA of hypothalamus, GR and MR mRNA of hippocampus in Guizhi+ Longgu Muli decoction group and Ganmai Dazaotang group were significantly higher than those in saline control group (P<0.05, P<0.01). The serum CORT level of Guizhi+ Longgu Muli decoction group was higher than that of normal saline group (P<0.01). The serum ACTH level of Polygalae Radix-Acori Tatarinowii Rhizome pair was significantly higher than that in saline control group(P<0.05). Conclusion::The mechanism of Longmu Guizhi decoction in treating ADHD is related to increase of the levels of CORT, ACTH and CRH in serum and the expressions of MR, GR, CRH in hypothalamus and GR and MR in hippocampus, so as to regulate the function of HPA axis. The order of the effect degree of each decomposition group on HPA axis function from high to low was Guizhi+ Longgu Muli decoction>Ganmai Dazao decoction>Polygalae Radix-Acori Tatarinowii Rhizome pair drug.
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OBJECTIVE: To study the chemical constituents of Zhishi Xiebai Guizhi decoction and its single agent by high performance liquid chromatography-mass spectrometry to provide a scientific basis for the quality evaluation and control. METHODS: Agilent XDB-C18(4.6 mm×250 mm, 5 μm) column was used for HPLC analysis with acetonitrile-water as mobile phase by gradient elution. Using liquid chromatography-mass spectrometry technology to collect data in positive and negative ion mode, combined with literature reports, the main chemical components of Zhishi Xiebai Guizhi decoction were analyzed and identified. RESULTS: A total of 19 compounds were identified from Zhishi Xiebai Guizhi decoction. The main components are naringin, neohesperidin, etc. The main component types include alkaloids, steroidal saponins, glycosides, flavonoids, etc. CONCLUSION: This study comprehensively clarified the chemical composition of Zhishi Xiebai Guizhi decoction, and it has important reference value for the identification and quality evaluation of Zhishi Xiebai Guizhi decoction.
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Objective@#To observe the effect of modified Gualou-Guizhi decoction combined with hyperbaric oxygen on muscle tension and motor function in stroke patients with spastic hemiplegia.@*Methods@#A total of 70 stroke patients with spastic hemiplegia met the inclusion criteria were randomly divided into the observation group and the control group, with 35 in each group. The control group was given the conventional treatment and hyperbaric oxygen treatment, while the observation group was treated with Gualou-Guizhi decoction on the basis of the control group. Lindmark scale was used to assess limb motor function, Fugl-Meyer Assessment Scale (FMA) was used to assess the degree of limb motor dysfunction, and Modified Ashworth Scale (MAS) was used to assess muscle tension. The root mean square (RMS) and frequency median (FM) of surface electromyography of quadriceps femoris were measured by automatic electromyography, and the clinical efficacy was evaluate.@*Results@#The total effective rate of the observation group was 91.4% (32/35), and the total effective rate of the control group was 71.4% (25/35). The total effective rate of the 2 groups was statistically significant (χ2=4.629, P=0.0314). After treatment, the scores of motor coordination ability and sensory function in the observation group were significantly higher than those in the control group (t value were 5.936, 5.182, all Ps<0.05), the FMA scores of upper and lower limbs were significantly higher than those in the control group (t value were 12.310, 11.996, all Ps<0.01), and the score of improved Ashworth muscle strength scale was significantly lower than that in the control group (t=5.083, P=0.031). After treatment, the EMG RMS (79.13 ± 7.02 vs. 68.45 ± 7.01 , t=5.697), FM (99.31 ± 9.65 Hz vs. 90.73 ± 9.49 Hz, t=5.382) of the observation group were significantly higher than those of the control group (P<0.05).@*Conclusions@#The application of Gualou-Guizhi decoction add and subtract combined with hyperbaric oxygen on muscle tension and motor function in stroke patients with spastic hemiplegia can improve the muscle strength of stroke hemiplegic patients and improve the motor dysfunction of the patients, which can help to promote the recovery of the movement function of the patientst.
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Objective: Under the guidance of traditional Chinese medicine theory, this paper used network pharmacology model to explore the effective components and mechanism of “treating different diseases with same method” of Chaihu Guizhi Decoction (CHGZD) in treating gastric ulcer and epilepsy, which provided modern medical evidence for the theory of “treating different diseases with same method” of traditional Chinese medicine. Methods: The chemical constituents and potential targets of CHGZD were collected by TCMSP and TCMID databases. Disease targets of gastric ulcer and epilepsy were obtained in PubMed, CTD, and OMIM databases. Cytoscape 3.6.0 software was used to map CHGZD for gastric ulcer and epilepsy. The pharmacodynamic basis and molecular mechanism of the “treating different diseases with same method” network, and the functional and pathway enrichment analysis of gene targets was analyzed by DAVID 6.8 and KOBAS 3.0. Results: A total of 198 kinds of chemical constituents, 417 target targets, 114 gastric ulcer disease targets, and 461 epileptic disease targets were collected from CHGZD. Network analysis showed that 152 active components such as quercetin, beta-sitosterol, wogonin, kaempferol, and saikosaponin a in CHGZD played a role in the treatment of gastric ulcers and epilepsy through 17 common targets including PTGS2, VEGFA, TP53, IL6, and TNF, and 62 pathways such as pathways in cancer, and proteoglycans in cancer. Conclusion: The similar efficacy network composed of 17 common targets in gastric ulcer and epilepsy was the basis for CHGZD to play the role of “different disease and common treatment”. A total of 152 components work together through 62 pathways and 17 pathways to achieve the effect of “treating different diseases with same method”, which provides modern medical evidence for the traditional Chinese medicine to treat gastric ulcer and epilepsy from the liver and spleen.
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Objective: The mechanism of Gualou Guizhi Decoction (GGD) in the treatment of lower limb spasm after stroke was analyzed based on network pharmacology. Methods: Using the TCMSP and SwissTarget Prediction platform to screen the main components and targets of GGD, the obtained target information was imported into Gephi software to build the active components-targets network of GGD. Genecard, DisGeNET, and TTD disease databases were used to screen target genes for stroke and lower limb spasm; Target protein interaction network was constructed by using STRING platform; KEGG pathways, and GO (Gene Ontology) function were analyzed by using ClueGO software and DAVID v 6.8 platform. Results: Flavonoids, organic acids, and saponins of GGD was applied to 49 key target genes, such as IL6, TNF, EGFR, ESR1, TP53, STAT3, and F2, etc; Forteen category biological processes including proliferation of striated muscle cells, bone remodeling, smooth muscle cells, muscle cells and endothelial cells proliferation were involved; Thirty signaling pathways, including TNF, MAPK, PI3K-Akt, ALS, serotonergic synapse, and neurotrophin, etc, were regulated. Conclusion: Various active ingredients of GGD has pharmacological effects such as anti-inflammatory, antioxidant, neurotrophic, and participate in some biological processes, such as muscle cell proliferation, so as to treat lower limb spasm after stroke from central nervous system and peripheral muscle tissue two-ways.
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Aim To reveal the effects of Guizhi decoction (G Z D) on allergic contact dermatitis by establishing the mouse allergic contact dermatitis model induced by fluoresciniso thiocyate (FITC) and culturing splenic lymphocytes. Methods BALB/c mice were sensitized by smearing the 1.5% FITC on the shaved abdomens on day 1 and day 2 and elicited on the right ear with 0. 6% FITC solution on day 6. GZD was administered from day 1 to day 7. Ear thickness was measured 24 h after elicitation. HE staining was performed for pathohistological examination. Interleukin-4 (I L - 4), IL-5, IL-9, interferon γ(IFN-γ) in ear tissue homogenates and IgE in serum were detected. The splenic lymphocytes were stimulated with ConA. Results The ear swelling was significantly suppressed by administering GZD. GZD reduced the infiltration of inflammatory cells and edema in the ear, and the levels of I L 4, IL-9, IFN7 and IgE. GZD could also reduce the expression of I L 4, IL-10, IFNγ and GATA3. Conclusions GZD could suppress allergic contact dermatitis elicited by FITC, which may result from inhibiting the differentiation of lymphocytes to Th2 cells.
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Wu-tou decoction (WTD) and Baihu-Guizhi decoction (BHGZD) as described in the Synopsis of the Golden Chamber have been used extensively for the treatment of rheumatoid arthritis (RA) with apparent therapeutic efficacy. However, characteristics of pharmacological effects and their underlying molecular mechanisms have not been fully elucidated due to a lack of appropriate scientific methodology. In the current study, we performed an integrative approach applying gene expression profiling and network analysis to examine the therapeutic effects and molecular mechanisms of WTD and BHGZD based on adjuvant-induced arthritis (AIA) animal model. Results demonstrated that both WTD and BHGZD could relieve the severity of arthritis in AIA rats, while the significant differences were observed in the changes of the withdrawal response scores and latency time of AIA rats treated with WTD and BHGZD. Mechanistically, our network pharmacology-based investigation demonstrated that the major candidate targets of WTD and BHGZD were significantly associated with several inflammation-immune regulatory pathways, such as Toll-like receptor signaling pathway, T cell receptor signaling pathway, cytokine-cytokine receptor interaction, chemokine signaling pathway, B cell receptor signaling pathway, antigen processing and presentation, Fc epsilon RI signaling pathway, natural killer cell mediated cytotoxicity, as well as leukocyte transendothelial migration. In particular, the major candidate targets of WTD were also involved in the regulation of hormone and energy metabolism, which might be imbalanced during RA progression. In conclusion, the current study revealed differences and similarities regarding the effects and network regulatory mechanisms of WTD and BHGZD. These findings may present a scientific basis for elucidation of mechanisms by which WTD and BHGZD alleviates RA.
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Guizhi decoction come from Typhoid Theory written by Zhang Zhongjing, a famous physician in the Han dynasty. It is called "the leading group of the group" by later doctors. At present, Guizhi decoction is widely used in treatment of many diseases of internal, external, gynecologic and other diseases. This article discusses the clinical application and mechanism of Guizhi decoction in two aspects. This article expounds that Guizhi decoction is widely used in colds, febrile diseases, various perspiration, digestive system diseases and respiratory diseases, Some diseases, such as ear, nose and throat disease, nervous system disease, cardiac autonomic neuropathy, and bone and joint disease. The mechanism of Guizhi decoction in the treatment of diseases may be related to the mechanism of biaxial regulation of body temperature and gastrointestinal motility, mucosal immune intervention, secretion of sweat glands, inflammation immune function and myocardial protective effect and so on.
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In order to study the effect of sediment of water extract of Guizhi decoction on the stability, clarity and peaks area, and characterize the chemical composition of the sediments, HPLC and MS methods were established. Through comparison of the common peak areas and the turbidity value of water extract and filtrate, the sediments could greatly change the common peak areas of the decoction (for more than 5 times of the study standard); at the same time, the turbidity value of the decoction could increase by （38.66±1.57）% in 48 h [particularly by （24.54±1.68）% in 6 h]. The test indicated that the sediments had an effect on the stability and clarity under the test conditions in Guizhi decoction. The study confirmed that the sediments were mainly derived from Cassia twig, Paeonia lactiflora and Glycyrrhiza uralensis. On the basis of the reference information, the accurate molecular weight and fragment ion information provided by LC-MS were analyzed, the molecular formula of sediments components A-F were determined, and the possible structural information of components B, C, D and F were deduced. It was suggested that the multi-index, multi-target and multi-angle analysis could ensure the quality of traditional Chinese medicine and the effect of clinical medication. The study also suggested the effect of the sediments on clinical application and the preparation of traditional Chinese medicine.
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OBJECTIVE:To study the potential targets of Guizhi decoction regulating Ying and Wei based oncorrespondence between formulation and syndromerelationship and reverse molecular docking technology. METHODS:Active ingredients related to Guizhi decoction were obtained by literature retrievals,and PharmMapper Server was used for reverse molecular docking for ac-tive ingredients. The potential receptors of Guizhi decoction were found on the basis of docking scores,then AutoDock Vina was conducted for positive molecular docking test to observe the affinity between the ligand and the receptor molecule. 75 rats were ran-domly divided into normal group,model group,Guizhi decoction high-dose,medium-dose,low-dose groups(12,8,4 g/kg),15 in each group. Except for normal group,rats in other groups were induced for models with disharmony between Ying and Wei. Af-ter modeling,rats were intragastrically administrated once a day,for 5 d. After administration,11β-HSD1 expression levels in adi-pose tissue and muscle tissue of rats were detected. RESULTS:Reverse molecular docking for active ingredients of Guizhi decoc-tion found that 11β-HSD1 was the frequent receptor,and positive docking test confirmed that uralsaponin b,glycyrrhetnic acid and carbenoxolone and so on had higher affinity with 11β-HSD1. Results of animal test showed,compared with normal group,11β-HSD1 expression levels in adipose tissue and muscle tissue in model group were increased (P<0.05);and compared with model group,11β-HSD1 expression levels in adipose tissue and muscle tissue in Guizhi decoction high-dose group were decreased (P<0.05). CONCLUSIONS:Guizhi decoction regulating Ying and Wei has certain correlation with 11β-HSD1,while the reverse molec-ular docking technology can provide a feasible technical way to studycorrespondence between formulation and syndromerelation-ship.
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Objective: To study the serum pharmacochemistry of Gualou Guizhi Decoction (GLGZD) as well as the material basis through analyzing the constituents absorbed in blood. Methods: A high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS) method was developed for the analysis on absorbed components in serum after ig administration of GLGZD to rats. The separation was achieved on a C18 column by gradient elution with acetonitrile-aqueous solution (containing 0.1% formic acid) as mobile phase. The ion acquisition was performed by full scan MS and MS/MS in negative ion mode.The serum after ig administration of GLGZD to rats, blank serum of rats, and GLGZD extracts sample were analyzed by HPLC-Q-TOF-MS. Results: Forty-two prototype compounds including monoterpene glycosides, flavonoids, phenolic acids, gingerols, triterpenoid saponins, galloylglucoses, and others were confirmed and identified in serum by comparing the retention time and mass spectrometry fragmentation characteristics with reference standards or literatures. Conclusion: The analysis of absorbed components of GLGZD in serum after administration by serum pharmacochemistry method would provide an experimental basis for revealing the real neuroprotective constituents of GLGZD in treating dysfunction after stroke.
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[Objective]Discussing the experiences on using the Modification of Guizhi Decoction plus Dahuang in the Treatise of Cold-Induced Disorders to treat paediatric diseases.[Methods]Selecting 4 paediatric cases that are all using Guizhi added Dahuang Tang to treat concurrent disease of Taiyang and Yangming Channels, concurrent disease of Taiyin and Yangming Channels, interior excess pattern of Taiyin which causing fever, eczema, constipation, abdominal pain,to discuss the train of thoughts in using the Modification of Guizhi Decoction plus Dahuang in the clinic.[Results] Using the Modification of Guizhi Decoction plus Dahuang in the Treatise of Cold-Induced Disorders with a flexible addition and subtraction can treat all kinds of paediatric diseases such as concurrent disease of Taiyang and Yangming Channels, concurrent disease of Taiyin and Yangming Channels, interior excess pattern of Taiyin.The 4 cases proved in this article all used the Modification of Guizhi Decoction plus Dahuang to treat paediatric exogenous high fever, eczema, constipation, abdominal pain, etc,on the basis of syndrome differentiation,using the Modification of Guizhi Decoction plus Dahuang ,or Xiaojianzhong Decoction plus Dahuang,with the addition and subtraction,to treat various of paediatric diseases caused by concurrent disease of Taiyang and Yangming Channels, concurrent disease of Taiyin and Yangming Channels, interior excess pattern of Taiyin ,and all obtained good effects. [Conclusion] Under the guidance of the six meridians syndrome differentiation,with the addition and subtraction of the Modification of Guizhi Decoction plus Dahuang,expand the scope of the application of classical prescription,and enhance the clinical effects.
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Objective To observe the therapeutic effect of Guizhi Decoction plus Yupingfeng Powder for chronic urticaria and its effect on serum total IgE level.Methods One hundred and twenty patients were randomly divided into treatment group,control group 1 and control group 2,40 cases in each group.The treatment group was treated with Guizhi Decoction,Yupingfeng Powder and Loratadine Tablets orally,the control group 1 was given intramuscular injection of Bacillus Calmette-Guerin polysaccharide nucleic acid and oral use of Loratadine Tablets,and the control group 2 was only given oral use of Loratadine Tablets.The course of treatment covered 5 weeks.The levels of serum total IgE in the three groups were determined before and after treatment,and the therapeutic effect was evaluated after treatment.Results (1) The total effective rate was 85.0％ in the treatment group,80.0％ in the control group 1,and 55.0％ in the control group 2.The effect of control group 1 and the treatment group was superior to that of the control group 2 (P＜ 0.05),but the difference was insignificant between the treatment group and control group 1 (P＞ 0.05).(2)Before treatment,the serum total IgE level of the three groups was higher than that of the normal control group (P ＜ 0.05).After treatment,the serum total IgE level of the three groups was obviously decreased (P ＜ 0.05 compared with that before treatment);the inter-group comparison results showed that the effect of the treatment group and control group 1 on decreasing the serum total IgE level was superior to that of the control group 2(P ＜ 0.05),while the effect of the treatment group was similar to that of the control group 1 (P ＞0.05).(3) During the treatment,blood routine examination indexes and hepato-renal function of the three groups showed no abnormal changes,neither adverse reaction was shown.Conclusion Guizhi Decoction plus Yupingfeng Powder exerts certain therapeutic effect for the treatment of chronic urticaria,and can decrease the serum total IgE level,thus to stabilize the curative effect and reduce the recurrence.
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Guizhi Decoction was one of the most commonly used traditional Chinese Medicine which possesses the effects of "jie-ji-fa-biao, regulating Ying and Wei". It was mainly used to treat mind-cold due to exogenous evils such as fever, headache, sweating, hate the wind, et al. Modern studies indicated that the chemical constituents of Guizhi decoction mainly include phenylpropanoid, monoterpenes, organic acids, flavonoids, triterpenoid saponins and so on. Pharmacological experimental studies had shown that Guizhi decoction could play a big role in dual-directional regulation on sweat gland, body temperature, immune function, gastrointestinal peristalsis, and blood pressure, and could also play the role of anti-inflammatory, antibacterial, antiviral, anti-allergic, analgesic, hypoglycemic, and cardiovascular protection. Many diseases such as internal, external, gynecological and pediatric diseases were treated in the clinical by using Guizhi decoction and its analogous formulae involving circulatory, immune, urinary, reproductive, endocrine, digestive, nervous and other systems. This article reviews the latest research progress of Guizhi decoction from three aspects: chemical constituents, pharmacological mechanism and clinical application. It will provide reference for further research and development of Guizhi decoction.
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The paper was aimed to establish a quality evaluation model for Gualou Guizhi decoction based on the chemical compositions and biological effects. Ultra high performance liquid chromatograph-mass spectrometer was used to analyze and determine 24 kinds of chemical compositions in Gualou Guizhi decoction, and then, biological activity effect was quantitatively assessed in a zebrafish neuronal injury model which was induced by mycophenolate mofetil (MMF). As a result, the established method for quality evaluation of Gualou Guizhi decoction based on the chemical compositions and biological effects is feasible, stable and reliable, which can provide reference for quality control of compound Chinese medicines.
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To investigate the characteristic methylation genes of pyretic arthralgia model in hot and dampness environment and the regulation effect of Baihu Guizhi decoction on this characteristic methylation genes. Plantar injection of CFA was used in hot and dampness environment to induce the pyretic arthralgia rat models. From 15th day after modeling, Baihu Guizhi decoction was given for 30 days. Foot volume was detected every 4 days after modeling, and HE staining was used to detect the histopathology of all rats' ankle joint at day 45.MeDIP-Seq sequencing method was used to detect the methylation level of knee joint synovial, and the method of difference sets was used to screen the characteristic methylation genesinpyretic arthralgia models.The contents of IL-1β, IL-17, TNF-α, EGF, IL-12p70, IL-4, IL-6 and IFN-γ in serum were measured by using suspension chips. The mRNA expression level of characteristic methylation genes was measured by qRT-PCR. The results suggested that as compared with adjuvant arthritis rat models(AA), the foot swelling and histopathology inpyretic arthralgia models (PA) were only slightly increased. As compared with normal group (NG), the wholegenome CpG island in both AA and PA groups was kept in a lower methylation state, furthermore, the methylation level was lowest in PA group; with 705 difference methylation genes in AA group and 2 418 difference methylation genes in PA group. As compared with AA, there were 1 287 difference methylation genes, including 974 down-regulated methylation genesand 313 up-regulated methylation genes. This difference methylation genes were mostly enriched in 32 KEGG pathways. Moreover, there were 52 characteristic methylation genes of PA models in promoter region, including 36 down-regulatedmethylation genes and 16 up-regulatedmethylation genes. After drug intervention, Baihu Guizhi decoction improved the foot swelling and pathological injury in PA models, significantly decreased the levels of IL-1β, TNF-α, EGF, VEGF, IL-17, IL-12p70, inhibited the mRNA expression levels of down-regulated methylation genes AHCY and RPL3, and promoted the mRNA expression levels of up-regulated methylation gene Agxt. In conclusion, unique methylation changes of synovial genes were present in PA models, and Baihu Guizhi decoction may adjust the methylation level of PA's characteristic methylation genes to achieve the therapeutic effect of pyretic arthralgia.
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OBJECTIVE:To establish a method for the contents determination of 9 components in Guizhi decoction,and com-pare the effects of traditional decoction method and the extracting machine decoction method on these contents in Guizhi decoction. METHODS:HPLC was performed on the column of Agilent Zorbax SB-C18 with mobile phaseof acetonitrile- 0.1% phosphoric ac-id(gradient elution)at a flow rate of 1.0 ml/min,the detection wavelength was 230 nm,254 nm and 280 nm,the column tempera-ture was 25℃,and the injection volume was 10μl. RESULTS:The linear range was 0.410 2-210.0μg/ml for gallic acid(r=0.999 9), 0.994 0-254.5μg/ml for albiflorin(r=0.999 9),1.636 0-1 675.0μg/ml for paeoniflorin(r=0.999 9),0.988 3-506.0μg/ml for liquiri-tin(r=0.999 6),0.987 3-31.59 μg/ml for coumarin(r=0.999 5),0.486 8-124.6 μg/ml for cinnamic acid(r=0.999 5),2.458 0-314.6μg/ml for cinnamaldehyde(r=0.999 5),0.034 3-1.096 μg/ml for 2-methoxy cinnamaldehyde(r=0.999 8),and 1.711 0-219.0 μg/ml for glycyrrdhizic acid (r=0.999 7);RSDs of precision,stability and reproducibility tests were lower than 5%,recoveries were 93.56%-103.19%(RSD=4.00%,n=9)、101.51%-107.32%(RSD=2.21%,n=9)、95.08%-103.76%(RSD=2.87%,n=9)、100.82%-105.73%(RSD=1.85%,n=9)、85.08%-89.12%(RSD=1.40%,n=9)、92.31%-99.12%(RSD=2.71%,n=9)、99.17%-102.32%(RSD=1.24%,n=9)、100.15%-103.98%(RSD=1.18%,n=9)、99.93%-102.61%(RSD=1.03%,n=9). The content of total effective components from the extracting machine decoction method was 4 565μg/g,that from the traditional decoc-tion method was 2 742 μg/g.CONCLUSIONS:The method is simple,stable and reproducible,and can be used for the simultaneous determination of 9 componentsin Guizhi decoction. The contents of gallic acid,albiflorin and 2-methoxy cinnamaldehyde are first re-ported. The total effective components from the extracting machine decoction method are higher than that from the traditional decoc-tion method.
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[ ABSTRACT] AIM:To investigate the preventive effect of Guizhi decoction on myocardial injury after chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA).METHODS:Wistar rats (n=54) were randomly divided in-to 6 groups.Methycobal and Guizhi decoction ( with different proportions between Ramulus Cinnamomi and Radix paeoniae Alba at 2∶1, 1∶2 or 1∶1) were pre-administered to the rats.Immunohistochemical method was used to observe the cardiac sympathetic nerve distribution.The contents of tyrosine hydroxylase (TH), choline acetylaminotransferase (ChAT) and growth-associated protein 43 (GAP-43) in the left ventricle were measured by ELISA.The serum levels of myocardial en-zymes and morphology of myocardial tissues were also observed.RESULTS:6-OHDA successfully induced cardiac sympa-thetic denervation as the contents of TH and GAP-43 in the left ventricle declined significantly.Compared with model group, the content of TH was elevated in both methycobal group and Guizhi decoction groups, while the content of GAP-43 was elevated only in Guizhi decoction groups.The serum levels of myocardial enzymes and the histopathological changes of the cardiac tissues were deteriorated after injection of 6-OHDA, indicating that the myocardial injury was established. Methycobal and Guizhi decoction normalized the abnormal change.Guizhi decoctions at 2∶1 and 1∶1 showed the best effi-cacy.CONCLUSION:6-OHDA-induced sympathetic denervation causes myocardial injury.Guizhi decoction with the proportions between Ranulus Cinnamomi and Radix paeoniae Alba at 2∶1 and 1∶1 effectively alleviate the myocardial injury after cardiac sympathetic denervation induced by 6-OHDA.