Application of Guizhi Fuling Pill in Gynecology

This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.

Exploring the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on weighted network pharmacology and molecular docking techniques

Objective:To explore the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on network pharmacology and molecular docking methods.Methods:The main active ingredients of Guizhi decoction were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and plant nervous disorder-related targets were screened from the Gene Cards database,OMIM database,and PharmGKB database.The intersection of the two was obtained.The intersection targets were used to draw a protein interaction network and a“Traditional Chinese Medicine-active ingredient-target”network using the STRING database and Cytoscape 3.9.1.The nodes in the“Traditional Chinese Medicine-active ingredient-target”network were weighted according to the“Jun-Chen-Zuo-Shi”principle.Kyoto Encyclopedia of Genes and Genomes,and gene ontology enrichment analysis were performed on the intersection targets.Molecular docking was used to verify the affinity between core targets and key ingredients.Results:A total of 225 effective components of Guizhi decoction were screened,among which 127 components could bind to 160 common targets and play a therapeutic role.The common targets were mainly enriched in 2785 gene ontology entries and 189 Kyoto Encyclopedia of Genes and Genomes pathways.Molecular docking confirmed that core targets could spontaneously bind to key ingredients.Conclusion:The key targets for the treatment of plant nervous disorders by Guizhi decoction are MAPK1,TP53,RB1,STAT3,MAPK3,MAPK14,etc.,which reflect the characteristics of the synergistic mechanism of traditional Chinese medicine with multiple components,targets,and pathways through the regulation of inflammatory signal pathways and oxidative stress processes.

Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral neuropathy.DATA SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December 2015.The search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in English.DATA SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control group.We assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 software.OUTCOME MEASURES：The primary outcomes were changes in symptoms and nerve conduction velocities.The secondary outcomeswere fasting blood glucose and hemorheological indexes.RESULTS：Sixteen randomized controlled trials,with a total of 1,173 patients,were included.Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment groups.No significant difference in fasting blood glucose was found between the treatment groups and the control groups（MD =-0.12,95%CI：-0.42–0.19,Z = 0.76,P = 0.45）.Plasma viscosity was significantly decreased after treatment（MD =-0.11,95%CI：-0.21 to-0.02,Z = 2.30,P = 0.02）.No significant difference in fibrinogen was detectable（MD =-0.53,95%CI：-1.28–0.22,Z = 1.38,P = 0.17）.Four trials reported that treatment groups experienced no adverse reactions.Adverse events were not mentioned in the other 12 trials.No trial reported the incidence of complications,quality of life outcomes,or health economics.CONCLUSION：HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities.Our study suggests that HGWWD may have significant therapeutic efficacy for the treatment of diabetic peripheral neuropathy.However,the methodological quality of the randomized controlled trials was generally low.Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction （GLGZD） is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurologi- cal function was assessed immediately after reperfusion using Longa＇s 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2＇-deoxyuridine （BrdU） as well as expression of the neural precursor marker doublecortin （DCX）, the astrocyte marker glial fibrillary acidic protein （GFAP） and the axon regeneration marker growth associated protein-43 （GAP-43）. GLGZD substan- tially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and in- creasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Clinical Study of Jiawei Huangqi Guizhi Wuwu Decoction (加味黄芪桂枝五物汤) in Preventing and Treating Peripheral Neuro-sensory Toxicity Caused by Oxaliplatin

Objective： To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction （加味黄芪桂枝五物汤, JHGWD） in treating neuro-sensory toxicity induced by oxaliplatin. Methods： A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. Results： The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients （64.5 % ） suffered from neuro-sensory toxicity in the treated group and 27 cases （87.1% ） in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group （P〈0.01）. Conclusion： JHGWD could prevent and reduce the occurence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.

Effect of Guizhi Fuling capsule and its extracts on human breast cancer cells proliferation

OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.

Study on the mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking

Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.

Effects of Guizhi Shaoyao Zhimu Decoction on Laboratory Indicators and Immune Functions of Patients with Rheumatoid Arthritis

[Objectives]To explore the effects of Guizhi Shaoyao Zhimu Decoction on laboratory indicators and immune functions of patients with rheumatoid arthritis.[Methods]A total of 110 patients with rheumatoid arthritis admitted to the Second Department of Orthopedics,the Affiliated Chinese and Western Medicine Hospital of Nanjing,Nanjing University of Chinese Medicine from December 2014 to December 2016 were selected as the research objects and divided into a control group and an observation group using the random number table method,with 55 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Guizhi Shaoyao Zhimu Decoction on the basis of the control group.Both groups were treated for one month.The clinical effects,improvement of clinical symptoms,laboratory indicators and immune function indicator levels between the two groups were compared;the incidence of adverse reactions in the two groups was counted.[Results]The total effective rate of the observation group was 92.73%,higher than that of the control group(78.18%)(P<0.05).Compared with that before treatment,after one month of treatment,the grip strength of the two groups increased,and the observation group was greater than the control group(P<0.05);the morning stiffness time and 20 m walking time of both groups were shortened,and the observation group was shorter than the control group(P<0.05);the number of joint tenderness,joint swelling,ESR,MPV,PDW,serum CRP,plasma IgA,IgG,IgM,RF levels in both groups decreased,and the observation group was lower than the control group(P<0.05);the serum C3 levels in both groups increased,and the observation group was higher than the control group(P<0.05).During the treatment,the incidence of adverse reactions in the observation group was 0.00%,which was lower than that in the control group(10.91%,P<0.05).[Conclusions]Using Guizhi Shaoyao Zhimu Decoction to treat rheumatoid arthritis can improve the laboratory indicators of patients,and enhance their immune functions,improve the curative effect,and the safety is high.

Meta-Analysis on Efficacy and Safety of Modified Guizhi Shaoyao Zhimu Tang with the Western Medicines in Treating Rheumatoid Arthritis

Objective: To assess the efficacy and safety of modified Guizhi Shaoyao Zhimu Tang (GSZT) with the Western medicines in treating rheumatoid arthritis. Methods: All the relevant studies were collected by searching the Pubmed, Web of science, Embase, Cochrane Library, SpringerLink, China National Knowledge Infrastructure (CNKI), VIP Journals database, and Wanfang database from their inception to October 2017. After the assessment, the eligible ones were subject to Jadad score. The meta-analysis was conducted by RevMan 5.3 software. Results: Totally 10 randomized controlled trials (RCTs) involving 962 patients were enrolled. The clinical efficacy of analysis showed that modified GSZT with the Western medicines can significantly improve the clinical total effective rate [OR = 4.64, 95%CI (3.03, 7.12), P &minus;14.58, 95%CI (&minus;16.49, &minus;12.68), P &minus;12.62 95%CI (&minus;18.69, &minus;6.54), P &minus;49.88, 95%CI (&minus;77.6, &minus;22.09), P &minus;5.34, 95%CI (&minus;5.86, &minus;4.82), P < 0.001]. The adverse events had been seen in both of the two groups, however, the clinical symptoms of the group on modified GSZT with the Western medicines were obviously reduced than the other one [OR = 0.25, 95%CI (0.10, 0.61), Z = 3.06, P < 0.01]. This system review shows that the modified GSZT with the Western medicines improved the clinical efficacy, symptoms and the blood biochemical indicators were improved significantly than that of Western medicines alone on rheumatoid arthritis. At the same time, it can reduce adverse effects and enhance safety.

Network pharmacology-based approach to investigate the mechanisms of Guizhi Fuling pill in the treatment of atherosclerosis

Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.

Effect of Guizhi Fuling Capsule on sex hormone level and tumor markers in patients with uterine fibroids

Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroids who were treated in our hospital from August 2016 to August 2017 were selected according to the order of treatment and divided into observation group and control group, 60 cases each. Mifepristone was administered to the control group and mifepristone combined with Guizhi Fuling Capsules was administered to the observation group. The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups.Result:The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups. After treatment, hemoglobin levels increased significantly in the two groups, VEGF, sex hormones FSH, LH and E2, tumor markers HE4, CA125, inflammatory cytokines TNF-α and IFN-γ levels decreased significantly. The hemoglobin level of the observation group was (117.09±11.51) g/L higher than that of the control group , and the level of VEGF was (0.69±0.06) pg/mL lower than that of the control group. The levels of sex hormone FSH, LH and E2 in the observation group were (15.87±1.56) U/L, (10.69±1.06) U/L and (4.95±0.51) pmol/L lower than those of the control group. The levels of HE4, CA125, TNF-α and IFN-γ gamma in the observation group were (52.47±5.24) pmol/L, (15.46±1.53) U/mL, (40.41±4.05) and (16.72±1.62) pg/mL lower than those of the control group.Conclusion:Guizhi Fuling Capsule can significantly improve the level of sex hormones and tumor markers, relieve inflammatory stress and improve the therapeutic effect.

Guizhi Fuling capsule can induce apoptosis of myeloma cells through the mitochondrial apoptosis pathway

Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.

Potential Mechanism of Huangqi Guizhi Wuwu Decoction for Cervical Spondylosis treatment based on Network Pharmacology

Objective:To study the potential mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of cervical spondylosis based on the network pharmacological method,and to provide a basis for clinical application and pharmacological research.Methods:TCMSP search was used to screen the main active compounds and related action targets of Huangqi Guizhi Wuwu Decoction,the standard names of action targets were obtained through the Uniprot database,and the"drug-target"interaction network was constructed by using Cytoscape3.6.1 software.The related targets of cervical spondylosis were obtained by searching GeneCards,OMIM,DisGeNET,and CTD databases,and the disease targets and drug targets were mapped by the Venny platform,and the intersection genes of them were the potential targets for drug treatment of this disease.Then,the intersection genes were input into the STRING database and Cytoscape 3.6.1 software,and the protein-protein interactions(PPI)network of"drug-disease intersection targets"was constructed,and we screened the core targets.Finally,GO biological function analysis and KEGG signaling pathway analysis of core targets were carried out through the DAVID database.Results:According to the screening conditions,74 effective compounds and 138 drug action targets of Huangqi Guizhi Wuwu Decoction were obtained,12179 genes related to cervical spondylosis were obtained,and the Venny platform analysis obtained 105 intersecting targets.With visual network processing by Cytoscape software,33 core targets were obtained by analyzing and calculating the core target degree values,which were JUN,PTGS2,NR3C1,TNF,IL6,TP53,EGFR,VEGFA,NOS3,IL1B,and so on.GO analysis showed that there were 133 items(P<0.05),involving adrenergic receptor activation,neurotransmitter receptor activation,nuclear receptor activation,catecholamine binding,etc.KEGG analysis obtained a total of 139 pathways(P<0.05),involving IL-17 signaling pathway,and tumor necrosis factor signaling pathway,relaxin signaling pathway,AGE-RAGE signaling pathway of diabetic complications,fluid shear stress,and atherosclerosis.Conclusion:the active components in Huangqi Guizhi Wuwu decoction may act on the core targets such as JUN,PTGS2,NR3C1,TNF,IL6,TP53,VEGFA through IL-17 signal pathway,tumor necrosis factor signal pathway,and AGE-RAGE signal pathway of diabetic complications,and exert their therapeutic effects.The research results can provide a basis for future basic and clinical research.

Effects of Chaihu Guizhi Ganjiang Decoction Combined with Standard Triple Therapy on Reducing Serum CagA and Hp-NAP in Patients with H.pylori-Related Gastritis

OBJECTIVE: To explore the effects of Chaihu Guizhi Ganjiang Decoction combined with standard triple therapy on treating H.pylori-related gastritis. METHODS: Eighty-two patients with H. pylori-related gastritis treated in our hospital from January 2016 to December 2017 were selected according to the random number table method and divided into experimental group and control group, with 41 patients in each group. The control group was treated with standard triple therapy, while the experimental group was additionally treated with modified Chaihu Guizhi Ganjiang Decoction. The venous blood of one elbow was taken before and after treatment. The concentrations of serum CagA and Hp-NAP were detected by enzyme-linked immunosorbent assay(ELISA). The symptoms were evaluated according to the change of symptom scores before and after the intervention. The H.pylori eradication rate was calculated. RESULTS: There was no significant difference in CagA and Hp-NAP concentrations between the 2 groups before intervention(P > 0.05). After intervention, CagA and Hp-NAP concentrations in experimental group were(19.21±6.27) ng/L and(24.37±6.10) ng/L respectively which were lower than(25.81±7.14) ng/L and(32.09±5.73) ng/L of control group. The differences were statistically significant(P < 0.05). The total effective rate of major symptoms in experimental group was 39 cases(95.12%), which was significantly higher than that of the control group(31 cases, 75.61%). There was statistically significant difference between the 2 groups(P < 0.05). The eradication rate of H.pylori was 38 cases(92.68%) in the experimental group, which was significantly higher than 31 cases(75.61%) of the control group. The difference between the 2 groups was statistically significant(P < 0.05). CONCLUSION: Chaihu Guizhi Ganjiang Decoction combined with standard triple therapy can effectively reduce CagA, Hp-NAP of serum level in patients with H.pylori-related gastritis, improve efficacy of symptoms and eradication rate of H.pylori, and is worthy of clinical promotion.

Application of Huangqi Guizhi Wuwu Decoction in Orthopaedics and Traumatology

The Huangqi Guizhi Wuwu Decoction(HQGZWWT)is composed of Huangqi(Astragali Radix),Shaoyao(Paeoniae Radix Alba),Guizhi(Cinnamomi Ramulus),Shengjiang(Zingiberis Rhizoma Recens),and Dazao(Jujubae Fructus)which has various pharmacological anti-inflammatory,analgesic,antioxidant,antitumor,lipid-lowering,and immunity-regulating activities.It has certain advantages in the treatment of orthopaedic diseases,such as cervical spondylosis,scapulohumeral periarthritis,lumbar disc herniation,knee osteoarthritis,rheumatoid arthritis,myofascial pain syndrome,etc.,with outstanding clinical efficacy,few adverse reactions,and high patient compliance.However,modern pharmacological researches on the whole prescription of HQGZWWT are insufficient and the therapeutic targets are not clear which needs further exploration.Besides,this prescription cannot treat ll orthopaedic diseases,so we should adhere to the thinking of four diagnostics in traditional Chinese medicine(TCM),select prescriptions based on syndrome differentiation,closely follow the pathogenesis,innovate and expand its scope of application,reflect the application advantages of this prescription in orthopaedics and traumatology and improve the total clinical efficiency.

Guizhi Fuling Wan reverses drug resistance by regulating PTEN and MTDH in ovarian cancer SKOV3/DDP Cells

Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and metadherin(MTDH).METHODS Guizhi Fuling Wan(GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition,Wistar rats were given GFW viagavage at 4 g·kg^(-1)·d^(-1),8 g·kg^(-1)·d^(-1),16 g·kg^(-1)·d^(-1),or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera,medium-dose sear,highdose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells.Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells.RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera.RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli.taxel,the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold,respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec.tively;there was a significant difference between the groups(P<0.01).RT-qPCR results showed that,compared with the blank serum,the sera can up-regulate the expression of PTEN mRNA and downregulate the expression of MTDH mRNA in a dose-dependent manner.Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement.CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH,up-regulation of PTEN and induction of apoptosis,providing with an experiment basis for the applica.tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.

Identification and characterization of chemical constituents in Mahuang Guizhi Decoction and their metabolites in rat plasma and brain by UPLC-Q-TOF/MS

Objective:Mahuang Guizhi Decoction(MGD),an essential herbal pair in traditional Chinese medicine,is able to release cold,fever and asthma,mainly containing alkaloids,flavonoids,phenylpropanoids and amino acids.However,the absorption and distribution of these four category compounds in vivo still remained unclearly.Methods:In our research,we utilized UPLC-Q-TOF-MS technique to identify the constituents within MGD,as well as the prototypes of MGD and their metabolites absorbed in plasma and brain.We further profiled the drug-time curve of prototypes and metabolites of MGD both in plasma and brain.Results:Our results showed that 105 constituents were characterized in MGD.Thirty of them could be absorbed into blood,and ten of them could be distributed into brain.We also discovered eight new bio-transformed metabolites in blood,and a half of which could pass through the blood–brain barrier.In addition,all components detected in vivo could be absorbed and distributed immediately.Conclusion:These findings provide an approachable method to analyze the potential bio-active compounds in MGD and their in vivo behaviors,which could promote the efficacious material basis study of MGD and the security of clinical utilization.

Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice

Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis(CIA) mouse model.Methods: DBA/1J female mice were used to establish the collagen-induced arthritis(CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay(ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors m RNA and protein levels after HGWD intervention in RAW264.7 cells.Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints,reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function.HGWD decreased the expression of m RNA for inflammatory factors and the protein expression levels of p-NF-ΚB and IL-17.Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway

Objective: To observe the effects of Guizhi Fuling Capsule(GZFLC) on myeloma cells and explore the mechanisms. Methods: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative(10%, 20% and 40%) groups, GZFLC(10%, 20%, and 40%)groups and a control group. Cell counting kit-8(CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie(ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide(JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), cleaved caspase-3,-9, cytochrome C(Cytc)and apoptotic protease-activating factor 1(Apaf-1). RPMI 8226 cells(2×107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC(840, 420, or 210 mg/kg per day,respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. Results: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells(P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential(P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3,-9,Cytc and Apaf-1 were increased(all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLCadministered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLCadministered groups revealed that the Cytc and Apaf-1 expression levels were increased(P<0.05). Conclusion:GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.

疏调气机法联合桂枝茯苓胶囊治疗子宫肌瘤的疗效及其对血清TGF-β_(1)、TSGF的影响

目的:探究疏调气机法联合桂枝茯苓胶囊治疗子宫肌瘤的疗效及其对血清转化生长因子β_(1)(transforming growth factor-β_(1),TGF-β_(1))、肿瘤特异性生长因子(tumor specific growth factor,TSGF)的影响。方法:将135例子宫肌瘤患者采用随机数字表法分为对照A组、对照B组和联合组,每组45例。3组均给予常规西药治疗,在此基础上,对照A组采用疏调气机法治疗,对照B组采用桂枝茯苓胶囊治疗,联合组采用疏调气机法联合桂枝茯苓胶囊治疗。比较3组疗效、不良反应发生率及治疗前后子宫肌瘤体积、子宫体积、子宫内膜厚度、中医证候积分、血清雌激素指标[雌二醇(estradiol,E_(2))、黄体生成素(luteinizing hormone,LH)、催乳素(prolactin,PRL)]、氧化应激指标[晚期氧化蛋白产物(advanced oxidation protein products,AOPP)、丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)]、TGF-β_(1)、TSGF水平。结果:联合组总有效率为97.78%(44/45),高于对照A组的84.44%(38/45)、对照B组的80.00%(36/45)(P<0.05);治疗后3组患者子宫肌瘤体积、子宫体积均小于治疗前,联合组小于对照A组、对照B组;子宫内膜厚度大于治疗前,联合组大于对照A组、对照B组(P<0.05);与本组治疗前比较,治疗后3组患者月经异常、下腹胀痛、面色晦暗积分均降低,联合组低于对照A组、对照B组(P<0.05);治疗后3组患者血清PRL、LH、E_(2)水平均低于治疗前,联合组低于对照A组、对照B组(P<0.05);治疗后3组患者血清SOD水平均高于治疗前,且联合组高于对照A组、对照B组,血清AOPP、MDA水平均低于治疗前,联合组低于对照A组、对照B组(P<0.05);与本组治疗前比较,治疗后3组患者血清TGF-β_(1)、TSGF水平均降低,联合组低于对照A组、对照B组(P<0.05);联合组不良反应发生率为13.33%(6/45),与对照A组的6.67%(3/45)、对照B组的8.89%(4/45)比较,差异无统计学意义(P>0.05)。结论:疏调气机法联合桂枝茯苓胶囊能提高子宫肌瘤临床疗效,下调血清TGF-β_(1)、TSGF水平,且具有一定安全性。