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AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.
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ObjectiveTo explore the mechanism of herbal pair Astragali Radix-Puerariae Lobatae Radix （AR-PLR） against type 2 diabetes mellitus （T2DM） based on network pharmacology and experimental verification. MethodThe active ingredients and targets of AR and PLR were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The related targets of T2DM were retrieved from disease databases and the common targets of drugs and diseases were extracted. The protein-protein interaction （PPI） network was analyzed and constructed by STRING and the network topology of key targets was analyzed by Cytoscape 3.7.1. Then gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analyses of core targets were carried out by DAVID to explore its possible molecular mechanism. The T2DM model was induced in rats by the high-fat diet combined with tail intravenous injection of streptozocin. The rats were divided into a normal group，a model group，a metformin group，and high-，medium- and low-dose AR-PLR groups. After four weeks of intragastric administration，the serum levels of fasting blood sugar （FBS），fasting insulin（FINS），aspartate aminotransferase（AST），alanine aminotransferase（ALT），triglyceride（TG），total cholesterol（TC），low-density lipoprotein cholesterin（LDL-C），high-density lipoprotein cholesterin （HDL-C），interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） of rats in each group were measured. The protein expression of insulin receptor substrate-2（IRS-2），phosphatidylinositol 3-kinase（PI3K），protein kinase B（Akt）， and forkhead box transcription factor O1（FoxO1） in rat liver was detected by Western blot. ResultA total of 131 core targets of AR-PLR in the treatment of T2DM were screened out by network pharmacology， where Akt1，mitogen-activated protein kinase 1 （MAPK1），TNF-α，and IL-6 were critical. As revealed by KEGG enrichment analysis， AR-PLR exerted the hypoglycemic effect mainly through the PI3K/Akt，TNF， and FoxO signaling pathways. Compared with the model group，the high- and medium-dose AR-PLR groups showed reduced FBS and FINS levels and increased glycogen level （P<0.05，P<0.01），all the AR-PLR groups showed decreased levels of AST，ALT，TG， and LDL-C （P<0.05，P<0.01）， the high- and low-dose AR-PLR groups showed decreased TC levels （P<0.05）. Compared with the model group， the high- and medium-dose AR-PLR groups showed reduced levels of IL-6 and TNF-α（P<0.05，P<0.01）， and the high-dose AR-PLR group showed increased expression of IRS-2， Akt， p-Akt， PI3K， and p-PI3K， and decreased expression of FoxO1 protein（P<0.05）. ConclusionAR-PLR has the characteristics of multi-component，Multi-target and multi-pathway in the treatment of T2DM. This herbal pair may regulate the PI3K/Akt/FoxO1 signaling pathway through IL-6， TNF-α， and other targets to affect insulin resistance， glycogen synthesis， gluconeogenesis， glucose transport， inflammation， immune response， and other processes， thereby treating T2DM.
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Objective:To explore the effect of radiofrequency heating on the morphology of articular cartilage in the knee and the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the synovium using a rabbit model of knee osteoarthritis (OA).Methods:Fifty-four male rabbits had OA induced in their right hind limbs using the modified Hulth method. They were then randomly divided into a model group, a cervus and cucumis polypeptide (CCP) group and a radiofrequency thermotherapy (RT) group, each of 18. The CCP group was injected with deer melon peptide intramuscularly every day, while the RT group was given daily radiofrequency hyperthermia treatment at 36.5-38.5 ℃. The model group was not provided with any special treatment. On the 6th, 12th and 18th day of the treatment, 6 rabbits in each group were sacrificed to resect the right femur′s medial condyle cartilage. The morphological characteristics of the cartilage were evaluated using modified Mankins scoring, while the contents of lL-1B and TNF-a in the synovial membrane were detected using enzyme-linked immuno-sorbent assays.Results:The average Mankins scores and the levels of IL-1β and TNF-α decreased significantly at each time point, and significant differences were observed among the three groups. In the RT group the average Mankins score as well as the IL-1β and TNF-α levels decreased significantly with time throughout the experiment.Conclusions:Radiofrequency hyperthermia is superior to the injection of deer melon polypeptide in knee osteoarthritis, at least in rabbits. The therapeutic mechanism may be related to the control of IL-1β and TNF- α levels in the synovial membrane.
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BACKGROUND: Hypoxic pulmonary hypertension is a key link in the progression from chronic obstructive pulmonary disease to cor pulmonale. Its severity is closely related to disease development and prognosis. Current treatments cannot prevent or reverse disease progression. Maxing Xiongting Mixture has significant effect on hypoxic pulmonary hypertension with the syndrome of intermingled phlegm and blood stasis. OBJECTIVE: To study how the Maxing Xiongting Mixture regulates relevant factors of lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis. METHODS: Seventy Sprague-Dawley rats, 5 weeks old, were randomly divided into normal group (n=10) and model group (n=60), where acute cor pulmonale model was prepared by injecting 50 mg/kg monocrotaline solution (1%) intraperitoneally, followed by forced smoking and swimming 6 days a week lasting for 4 weeks. Except for 10 rats in the normal group, there were 46 model rats in the model group. According to the normal distribution of body mass, 40 rats were selected and randomly divided into 4 groups: model group, high-dose Maxing Xiongting Mixture group (MH), low-dose Maxing Xiongting Mixture group (ML) and fasudil group, with 10 rats in each group. Rats in MH and ML groups were respectively given Maxing Xiongting Mixture at 20 g/(kg·d) and 5 g/(kg·d), respectively and those in the fasudil group were given fasudil at a dose of 10 mg/(kg·d). Other groups were given equal amount of saline. Administration was given intraperitoneally and intragastrically, once a day for 14 days in total. RT-PCR was used to test the expression of factors related to lung reshaping and vascular remodeling, including RhoA, stromelysin 1 and tumor necrosis factor-α mRNAs. An approval for the study was obtained from the Ethics Committee of Chengdu University of Traditional Chinese Medicine (approval No. 2017-03). RESULTS AND CONCLUSION: Compared with the model group, the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs were significantly lowered in the MH group (all P 0.05). To conclude, Maxing Xiongting Mixture, which is similar to fasudil, intervenes lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis by inhibiting the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs.
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Objective: To explore the effects and related mechanism of heat-sensitive moxibustion plus clomifene citrate capsules for infertility due to polycystic ovary syndrome (PCOS). Methods: A total of 70 patients were randomized into a control group and an observation group by the random number table method, with 35 cases in each group. The control group was treated with clomifene citrate capsules, while the observation group was treated with heat-sensitive moxibustion on the basis of the medications in the control group. The treatment course lasted for 6 menstrual cycles. The endometrial thickness and ovarian volume of the patients were measured before and after treatment. The levels of serum sex hormones, tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) were detected. Follow-up was performed for 1 year after treatment, and the pregnancy rate was recorded. Results: After treatment, the endometrium of the patients in both groups was significantly thickened, the ovarian volume was significantly reduced, and the intra-group differences were statistically significant (all P<0.05). The endometrium thickness and ovarian volume in the observation group were significantly different from those in the control group (both P<0.05). After treatment, the levels of serum testostrn (T) and luteinizing hormone (LH) in both groups decreased significantly, the level of estradiol (E2) increased obviously, and the intra-group differences were statistically significant (all P<0.05). The levels of serum T and LH in the observation group were lower than those in the control group, and the E2 level in the observation group was higher than that in the control group, and the between-group differences were statistically significant (all P<0.05). After treatment, the levels of serum TNF-α and NF-κB of the patients in both groups decreased, and the intra-group differences were statistically significant (all P<0.05). The levels of serum TNF-α and NF-κB in the observation group were significantly lower than those in the control group (both P<0.05). After 1-year follow-up, the pregnancy rate was 20.0％ in the control group, versus 51.5％ in the observation group. The pregnancy rate in the observation group was higher than that in the control group, and the difference was statistically significant (P<0.05). Conclusion: The treatment of heat-sensitive moxibustion plus clomifene citrate capsules can increase the endometrium thickness, reduce the ovarian volume, improve the status of serum sex hormone disorders, and increase the conception rate in patients with infertility due to PCOS, which may be related to the adjustment of the levels of immune inflammatory factors such as serum TNF-α and NF-κB.
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Objective:To investigate the effect of maternal intervention of Zuoguiwan on the improvement of serum and pancreatic index in rats of gestational diabetes mellitus(GDM). Method:The GDM pregnant rats were replicated by monogamous cage and introneal injection of streptozotocin (STZ). The pregnant rats were randomly divided into normal group, model group, insulin group (20 U·kg-1), and low, medium and high-dose Zuoguiwan groups (2.5，5.0，10.0 g·kg-1). The insulin group was given hypodermic injection of portal winter insulin, all drug groups were respectively administrated with corrsponding drugs for 2 weeks, once a day. Meanwhile, control group and model group were given physiological saline by gavage. After that, the levels of serum insulin, fasting plasma glucose（FBG）, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA), protein and gene expression levels of Pancreas-duodenal homologous box factor-1 (PDX-1) were respectively detected by Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Result:Compared with normal group, FBG, TNF-α and IL-6 levels of pregnant rats in model group increased significantly (P<0.01), the level of IL-8 increased uniformly (P<0.05), and serum insulin level, protein and gene expression levels of PDX-1 decreased significantly (P<0.01). Compared with model group, FBG and serum IL-8 levels of pregnant rats in insulin group were significantly lower (P<0.01), while serum insulin level, protein and gene expression levels of PDX-1 increased significantly(P<0.01). FBG, IL-8, IL-6 and TNF-α levels in serum of pregnant rats in medium-dose Zuoguiwan group decreased obviously, meanwhile serum insulin level, protein and gene expression levels of PDX-1 increased significantly (P<0.01). Conclusion:Zuoguiwan may promote the secretion of insulin by reducing the serum inflammatory factors in GDM rats, and at the same time up-regulate the expression of PDX-1 protein and gene, so as to restrain insulin resistance, reduce the damage of pancreatic cells and improve the blood glucose of rats.
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Objective::To define the clinical efficacy of modified Taohe Chengqitang combined with colon hydrotherapy in patients with severe nonalcoholic fatty liver disease (NAFLD) accompanied by phlegm-heat stagnation syndrome and its mechanism. Method::Totally 100 patients with severe NAFLD by phlegm-heat stagnation syndrome were enrolled in the study.They were all given Shanzha Xiaozhi capsule.According to the random number table, the patients were randomly divided into the observation group (50 patients, colon hydrotherapy combined with traditional Chinese medicine) and the control group (50 patients, Shanzha Xiaozhi capsule alone). The observation period was 4 weeks.The therapeutic effect of colon hydrotherapy was verified through determinations of the liver function, blood lipid, insulin resistance index (IRI), controlled attenuation parameter (CAP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) before and after treatment.The mechanism of colon hydrotherapy combined with modified Taohe Chengqitang was preliminarily analyzed based on changes of IR, TNF-α and IL-6. Result::Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), total cholesterol (TCH), triglyceride (TG), fasting plasma glucose (FPG), fasting insulins (FINS), IRI, CAP, TNF-αand IL-6 of NAFLD patients in both of two groups were significantly lower than those before treatment (P<0.01). ALT, AST, γ-GT, TCH, TG, FPG, IRI, CAP, TNF-α and IL-6 in observation group were significantly lower than those in the control group after treatment (P<0.01). FINS in observation group was significantly lower than that in the control group (P<0.05). Conclusion::Colon hydrotherapy combined with modified Taohe Chengqitang is an effective method for treating NAFLD accompanied by phlegm-heat stagnation syndrome.Its mechanism may be mainly correlated with the reduction of IRI, serum TNF-α and IL-6.The course of colon hydrotherapy, the therapeutic mechanism and the long-term efficacy need to be further studied in the future.
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OBJECTIVE: To compare the effect of electroacupuncture (EA) of acupoint group for "reinforcing the kidney and regulating Governor Vessel" and acopoint group for "reinforcing the kidney and lung and regulating Governor Vessel" on lear-ning-memory ability and expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) proteins in the hippocampus and prefrontal cortex (PFC) in Alzheimer's disease （AD） rats, so as to explore the efficacy of the two acupoint groups and mechanisms underlying improvement of AD. METHODS: Forty male SD rats were randomly divided into control, sham operation, model, "Baihui" + "Shenshu" (GV20+BL23, for "reinforcing the kidney and regulating Governor Vessel") EA and GV20+BL23+ "Feishu" (BL13, GV20+BL23+BL13, for "reinforcing the kidney and lung and regulating Governor Vessel") EA groups (n=8 rats in each group). The AD model was established by bilateral injection of amyloid β peptide （Aβ25-35，10 μL) into bilateral hippocampus, and rats of the sham operation group received injection of normal saline. After successful establishment of the model，EA (2 Hz, 2 mA) was applied to these acupoints for 15 min, once daily for 10 days. Then, the learning-memory ability was assessed by using Morris water maze tests, and the expression levels of TNF-α and IL-1β proteins in the PFC and hippocampus tissues were detected by using Western blot. RESULTS: Following modeling, the average escape latency of place navigation test were significantly increased (P0.05). CONCLUSION: EA of both GV20+BL23 and GV20+BL23+BL13 acupoint can improve learning-memory ability of AD rats, which is associated with their effects in down-regulating the expression of IL-1β and TNF-α in the PFC and hippocampus to reduce inflammatory reaction. There were no significant differences between the two acupoint groups in the therapeutic effects.
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Objective: To compare the antidiarrheal effects of Mongolian medicine, Holarrhena antidysenterica, Forsythia suspensa and Cynanchum thesioides on diarrhea model rats and investigate its effects on serum DAO (diamine oxidase), cAMP (cyclic adenosine phosphate), TNF-α (tumor necrosis factor-α), ATPase and calcium ions. Methods: The normal control group, model group, H. antidysenterica low-dose and high-dose groups, F. suspensa low dose and high-dose groups, C. thesioides low dose and high dose groups were set. Except the normal control group, the other groups were ig administrated water decoction of Cassia angustifolia to establish diarrhea model; After the success of the model, the rats in treatment groups were administrated by gastric drug for 7 d, the type mental state, diarrhea and body weight changes were observed. the abdominal aortic blood was obtained at the last day of fasting 12 h after the administration. DAO, cAMP, TNF-α, ATP enzyme, OD value of the calcium ions in serum were determined by using ELISA (enzyme-linked immune detection reagent) kits. Results: General status: except for the normal group, the mental state of the rats in the other groups was depressed after modeling, the fur color of them was significantly decreased and the body weight was decreased. The diarrhea rate was 100% on the 4th day after modeling. Compared with the model group, there were significant differences in the number of loose stools, grade of loose stools and diarrhea index (P < 0.05, 0.01) in each administration group. The serum DAO, TNF-α, ATPase, cAMP and calcium ion OD values were compared: the serum concentrations of DAO in H. antidysenterica low dose group, C. thesioides low dose group and F. suspensa high and low dose groups of rats were significantly lower than model group with significant differences (P < 0.05), and were significantly higher than normal group. The serum concentration of TNF-α in C. thesioides high and low dose groups were lower compared with model group (P < 0.05). The serum ATPase in C. thesioides high and low dose groups had significant difference (P < 0.05) compared with model group. The serum concentration of cAMP in H. antidysenterica high-dose group and F. suspensa low-dose group was significantly lower compared with model group with significant differences (P < 0.05). Serum Ca2+ concentration in the drug administration groups was significantly different from that in the model group (P < 0.05). Conclusion: The antidiarrheal effect of C. thesioides is better than that of H. antidysenterica and F. suspensa.
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We evaluate the therapeutic effects of baicalein on chemotherapy-induced intestinal mucositis (CIM) in mice. The role of gut microflora regulation in the therapeutic effects of baicalein was investigated meanwhile. Male Balb/c mice were randomly divided into three groups including normal control group, model group and experimental group. Except for normal control group, mice were injected with 5-fluorouracil and irinotecan to induce CIM. Animal welfare and experimental procedures comply follow the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Baicalein significantly reduced disease activity index (DAI) of CIM mice and decreased the content of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum. There were significant differences in the composition of the gut microbiota among groups according to the analysis of α diversity, β diversity, and the species differences. Compared with the normal control group, the Ruminococcaceae_UCG_014 and unclassified_f_Lachnospiraceae in mice of model group were significantly decreased while Bacteroides, Escherichia_Shigella, Enterococcus, Parabacteroides, Clostridium_ sensu_stricto_1, and Lactococcus were significantly increased. Baicalein significantly decreased the abundance of Bacteroides, Escherichia_Shigella, Parabacteroides, Enterococcus, Clostridium_sensu_stricto_1, and Lactococcus. Meantime, norank_f_Muribaculaceae was notably increased by baicalein. The content of IL-6 and TNF-α in the serum of the three groups were positively correlated with the abundance of Clostridium_sensu_ stricto_1, Lactococcus, Bacteroides, and Enterococcus according to correlation analysis. This study suggested the potential therapeutic effect of baicalein on CIM in mice. Regulation of gut microbiota probably plays a critical role in the therapeutic effects of baicalein.
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OBJECTIVE@#To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism.@*METHODS@#A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups.@*RESULTS@#①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05).@*CONCLUSION@#①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.
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Humans , Acupuncture Points , Acupuncture Therapy , Biomarkers , Blood , C-Reactive Protein , Fatigue , Therapeutics , Interleukin-6 , Blood , Neoplasms , Therapeutics , Quality of Life , Receptors, Tumor Necrosis Factor, Type I , Blood , Tumor Necrosis Factor-alpha , BloodABSTRACT
OBJECTIVE: To explore the effect of electroacupuncture treatment on the levels of cortisol and immune factors in patients with occupational noise-induced deafness(ONID) combined with depressive symptoms. METHODS: A total of 78 ONID patients combined with depressive symptoms were randomly divided into control group(40 cases) and electroacupuncture group(38 cases) by a random number table method. The control group received routine therapy, while the electroacupuncture group was treated with routine therapy plus electroacupuncture on alternate days, 3 times a week for 4 consecutive weeks. The levels of salivary cortisol, as well as the serum levels of cortisol, tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and C-reactive protein(CRP) of the two groups were observed and compared before and after treatment. RESULTS: Before treatment, the levels of saliva cortisol in the morning and night, and the serum levels of cortisol, IL-6, TNF-α and CRP in the two groups were compared, and the differences were not statistically significant(P>0.05). After treatment, the serum cortisol level of patients in electroacupuncture group reduced than that before treatment in the same group(P<0.05). However, there was no significant difference in the levels of salivary cortisol in the morning and night, and serum cortisol before and after treatment both in control group and electroacupuncture group(P>0.05). After treatment, the serum levels of IL-6 and TNF-α decreased in electroacupuncture group as compared with those before treatment and those after treatment in control group(P<0.01). CONCLUSION: Electroacupuncture treatment could reduce the levels of TNF-α and IL-6 in serum of ONID patients combined with depressive symptoms. The regulation of electroacupuncture on the inflammatory cytokines may be one of the mechanisms in treating ONID combined with depressive symptoms.
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Rheumatoid Arthritis is a kind of chronic autoimmune diseases mainly involving joint, which is characterized by systemic inflammatory response.Studies have shown that Rheumatoid arthritis patients showed associated antineutrophil cytoplasmic antibody (ANCA) and inflammatory cytokines such as interleukin (IL) , tumor necrosis factor (TNF) increased, the positive of ANCA and the increase of IL-1, IL-6, TNF-αare especially seen in the Rheumatoid arthritis patients who have inflammatory reaction, and which are roughly equal to the articular synovitis pathological mechanism of wind dampmess heat accumulation pattern in the traditional Chinese medicine.The treatment for Rheumatoid arthritis patients, Western treatment is use the methotrexate (MTX) as basic drugs, combined with other drugs to control the positive of ANCA and the higher of IL-1, IL-6, TNF-α.And combining traditional Chinese medicine treatment, the effect is not only at to increase Western effection but also be able to reduce the side effects of Western medicine.Therefore, the research of combined rheumatoid factor ANCA, IL-1, IL-6, TNF-αdetection is benefit to diagnosing rheumatoid arthritis.
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OBJECTIVE@#To explore the clinical effect of acupuncture and the potential effect mechanism in patients with premature ovarian failure.@*METHODS@#A total of 104 patients with premature ovarian failure were randomized into an acupuncture group and a western medication group, 52 cases in each one. In the western medication group, the conjugated estrogens tablets were prescribed for oral administration, 0.625 mg each time, once a day, consecutively for 21 days. On the 16th day of medication with conjugated estrogens tablets, the oral administration of medroxyprogesterone acetate tablets were supplemented, 10 mg each time, once a day, consecutively for 5 days, and then, these two kinds of western medication were discontinued for 1 week. A total of 3 cycles were required in treatment with 28 days as an artificial cycle. In the acupuncture group, acupuncture was applied. Two groups of acupoints were selected. The first group of acupoints were stimulated before ovulation and the acupoints were Guanyuan (CV 4), Guilai (ST 29), Taichong (LR 3), Taixi (KI 3), Xuehai (SP 10), Sanyinjiao (SP 6), Zigong (EX-CA 1), Yinlingquan (SP 9), Zusanli (ST 36), Shuidao (ST 28), Dahe (KI 12) and Tianshu (ST 25). The second group of acupoints were stimulated after ovulation and the acupoints included Ciliao (BL 32), Shiqizhui (EX-B 8), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Pishu (BL 20). The therapeutic effect was observed and compared in the patients between the two groups, as well as the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and the levels of serum luteinizing hormone (LH), follicule stimulating hormone (FSH) and estradiol (E) before and after treatment.@*RESULTS@#The total effective rate was 90.4% (47/52) in the acupuncture group, higher than 67.3% (35/62) in the western medication group (<0.05). After treatment, the expressions of IFN-γ and TNF-α in the acupuncture group were obviously lower than the western medication group (<0.05). Except for serum LH after treatment, at the end of treatment and in 30 days and 90 days after treatment, the levels of serum E in the acupuncture group were higher obviously than the western medication group and the levels of serum LH and FSH were lower obviously than the western medication group (all <0.05).@*CONCLUSION@#Acupuncture promotes the regular menstruation, effectively regulates the levels of serum LH, FSH and E and improves the pituitary gland and the ovary endocrine in the patients with premature ovarian failure. Such effect may be related to the the improvements in the expressions of IFN-γ and TNF-α, the inhibition of the apoptosis of ovarian granulosa cells, the recovery of ovarian function and the enhancement of reserve capacity.
Subject(s)
Female , Humans , Acupuncture Points , Acupuncture Therapy , Interferon-gamma , Blood , Primary Ovarian Insufficiency , Blood , Therapeutics , Tumor Necrosis Factor-alpha , BloodABSTRACT
OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the expression of Interleukin (IL)-10 mRNA, IL-6 mRNA and tumor necrosis factor (TNF) - α in the parahippocampal gyrus of cerebral ischemia (CI) rats, so as to explore its molecular mechanisms underlying improvement of CI. METHODS: A total of 64 male SD rats were randomized into normal control, model, medication and scalp-acupuncture groups (n＝16 rats in each group). The focal CI model was established by middle cerebral artery occlusion. Intraperitoneal injection of Ammonium Pyrrolidine Dithiocarbamate (100 mg•kg－1•d－1) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS6), followed by twirling the needles at 100 cycles/min for 1 min, once again every 10 min during 20 min' needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－4 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schabitz's (2004) methods, respectively. The expression levels of IL-10 mRNA and IL-6 mRNA were detected by fluorescence quantitative PCR, and the expression of TNF-α was detected by immunohistochemistry. RESULTS: After modeling, the neurologic deficit and neurological function scores and the expression levels of IL-10 mRNA, IL-6 mRNA and TNF-α protein in the parahippocampus were significantly increased in the model group than in the normal control group (P<0.01). Following the intervention, the neurologic deficit and neurological function scores as well as IL-6 mRNA and TNF-α protein expression were significantly down-regulated in both scalp-acupuncture and medication groups (P<0.05), and the expression of IL-10 mRNA was obviously increased (P<0.05) relevant to the model group. CONCLUSION: Scalp-acupuncture can improve neurologic function in CI rats, which is related to its effects in up-regulating the expression of IL-10, then down-regulating the expression of IL-6 and TNF-α (reducing inflammatory response) in the parahippocampal gyrus.
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OBJECTIVE: To observe the effect of herbal cake-partitioned moxibustion (Moxi) on tumor necrosis factor (TNF)-α/ TNF receptor 1 (TNFR1)-associated death domain (TRADD) / Fas-associated death domain (FADD) pathway-mediated apoptosis of intestinal epithelial cells in Crohn's disease (CD) rats, so as to explore its underlying mechanisms in the treatment of CD. METHODS: Forty-eight SD male rats were randomly divided into normal, model, Moxi and medication groups (n＝12 rats in each). The CD model was established by intra-annual perfusion of 2，4，6-trinitrobenzene sulfonic acid (TNBS) solution (TNBS∶50% alcohol＝2∶1, 3 mL/kg), once every 7 days, 4 times altogether. For rats of the Moxi group, moxibustion was given to "Tianshu" (ST25) and "Qihai" (CV6), two moxa-cones every time, once daily for 10 days. For rats of the medication group, intragastric perfusion of mesalazine solution was given twice daily for 10 days. After the treatment, the colonic epithelium tissue was sampled. The epithelial cells were purified and cultured to establish an in vitro intestinal epithelial barrier, and added with TNF-α (a pro-inflammatory factor, 100 ng/mL) in the culture medium for 24 h for making an increased epithelial permeability model. The permeability of intestinal epithelial cell barrier was evaluated by detecting the fluorescence yellow transmittance of the TNF-α-incubated cell medium. Western blot was used to detect the expression levels of TNFR1, TRADD, receptor-interacting protein 1 (RIP1), FADD and zinc finger protein A20 (A20, a ubiquitination enzyme for inhibiting activation of TRADD and RIP1) of the cultured intestinal epithelium cells. The apoptosis of the TNF-α-incubated intestinal epithelial cells was detected by flow cytometry. RESULTS: After modeling and compared with the normal group, the fluorescence yellow transmittance of intestinal epithelia cells, apoptosis rate, and expression levels of TNFR1, TRADD, and RIP1 proteins were significantly increased (P<0.001, P<0.01), and the expression of A20 was significantly decreased (P<0.01) in the model group. In comparison with the model group, the fluorescence yellow transmittance of intestinal epithelial cells, the apoptosis rate and expression levels of TRADD, RIP1 and FADD were remarkably down-regulated (P<0.001, P<0.01), and the expression of A20 was significantly up-regulated (P<0.01) in both the Moxi and medication groups. CONCLUSION: Herbal cake-partitioned moxibustion may down-regulate the permeability of intestinal epithelial barrier and the apoptosis of intestinal epithelial cells by way of suppressing TNF-α-mediated cellular apoptosis pathway of intestinal epithelium in CD rats.
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Objective:To observe the effects of moxibustion on serum levels of interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α), and to explore the effects of moxibustion on inflammatory damaging factors in experimental rheumatoid arthritis (RA) model rats; the relationship between the therapeutic effect of moxibustion on RA and the change in the Toll-like receptor (TLR) signaling pathway was analyzed using Toll-like receptor 4 (TLR4) antagonists and agonists. Methods:Fifty Sprague-Dawley (SD) rats were divided into a normal group, a model group, a moxibustion group, a moxibustion plus TLR4 agonist group (agonist group) and a moxibustion plus TLR4 antagonist group (antagonist group) according to the random number table, with 10 rats in each group. Except the normal group, rats in the other four groups were subjected to model preparation with the wind, cold and wet environmental factors plus Freund's complete adjuvant (FCA). Rats in the normal and model groups were not treated; rats in the moxibustion, agonist and antagonist groups started to be treated with the moxibustion (cigarette-type moxa) at bilateral Shenshu (BL 23) and Zusanli (ST 36) from the 4th day after the successful modeling, for 20 min each time with a total of 10 d. Rats in the agonist and the antagonist groups were injected with TLR4 agonist or antagonist [0.1 mg/(kg·bw)] via the tail vein 30 min before moxibustion. The concentrations of serum IL-6, IL-8 and TNF-α in each group were determined by enzyme-linked immunosorbent assay (ELISA). Results:Compared with the normal group, in the model group, the rat's right hind paw swelling was significantly obvious (P<0.01), there was a lot of inflammatory infiltration in the synovial tissues, the surface of the synovial membrane was unsmooth, the synovial membrane was hyperplasia and thicker, and the serum IL-6, IL-8 and TNF-α concentrations increased significantly (P<0.05). Compared with the model group, the paw swelling degrees of the rats in the moxibustion, the agonist and the antagonist groups reduced significantly (allP<0.01); the swelling degree in the antagonist group was milder than that in the agonist group, but the between-group difference was not statistically significant (P>0.05); inflammatory infiltration and synovial membrane hyperplasia in the synovial tissues of the moxibustion group and the antagonist group were all relieved differently; the decrease of synovial layer number in the moxibustion group was more obvious, and there were no obvious improvements in inflammatory infiltration and synovial thickness in the agonist group; the concentrations of IL-6, IL-8 and TNF-α in the moxibustion group were decreased, and the differences in the IL-6 and TNF-α concentrations were statistically significant (allP<0.01); there was no significant between-group difference in the IL-8 concentration (P>0.05); the concentrations of serum IL-8 and TNF-α in the agonist group increased significantly (both P<0.01), while the IL-6 concentration decreased without significant difference (P>0.05); the concentrations of IL-6 and IL-8 in the antagonist group decreased but the between-group differences were statistically insignificant (bothP>0.05), and the TNF-α concentration significantly increased (P<0.05). Compared with the moxibustion group, IL-6, IL-8 and TNF-α concentrations increased in the agonist group, and the differences in the IL-8 and TNF-α concentrations were statistically significant (both P<0.01); the concentrations of IL-6, IL-8 and TNF-α increased in the antagonist group, and the differences in the IL-6 and TNF-α concentrations were statistically significant (bothP<0.01); there was no significant difference in the IL-8 concentration between the groups (P>0.05). The serum levels of IL-6, IL-8 and TNF-α in the antagonist group were lower than those in the agonist group (allP<0.05). Conclusion:Moxibustion at Shenshu (BL 23) and Zusanli (ST 36) can reduce the joint swelling degree and inflammation in synovial tissue of RA model rats, decrease the serum levels of IL-6, IL-8 and TNF-α in RA model rats; the decreases of IL-6 and TNF-α are more significant than the decrease of IL-8; TLR4 agonist and antagonist can significantly attenuate the effect of moxibustion in inhibiting releases of IL-6, IL-8 and TNF-α, so that the change in TLR signaling pathway affects the effect of moxibustion in inhibiting the releases of IL-6, IL-8 and TNF-α.
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It is now thought that atherosclerosis,although due to enhanced lipid deposition,is mainly the result of a series inflammatory process.Total saponins of Aralia elata (Miq)Seem(TASAES)from the Chinese traditional herb Longya Araliachinensis L.,a folk medicine used for treating various diseases, increasing energy and improving the body′s ability to prevent hypoxia in Asian countries has attracted widespread attention. However, the ability of TASAES on inflammation-triggered vascular endothelial cell injury, a key early event in the pathogenesis of atherosclerosis, and its potential mechanisms of this protection have never been demonstrated. The present study determined the anti-inflammatory and anti-apoptoticactivities and protective mechanisms of the total aralosides of Araliaelata(Miq)Seem (TASAES) ameliorate tumor necrosis factor-α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury. Our results indicate that TASAES pretreatment provided cytoprotective effects by suppressing TNF-α-induced HUVECs apoptosis, mitochondrial membrane depolarization, caspase-3 activation, and modulation of inflammatory factors (IL-6, MCP-1 and VCAM-1), meanwhile inhibiting NF- κB transcription. Furthermore, the effect was correlated with the activation of the PI3K/Akt signal pathway. Blocking Akt activation with the PI3K inhibitor LY294002 effectively reversed the protective effect of TASAES against TNF-α-induced cell apoptosis.Moreover,the PI3K inhibitor partially blocked the effects of TASAES on the increasing of Bcl-2 and Bcl-xl protein expression,and inactivation of Bax protein expression. In conclusion, the results showed that TASAES decreased the inflammation and apoptosis of HUVECs caused by TNF-α treatment,and PI3K played a crucial role in enhancing cell sur-vival during this process.
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<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) on inflammatory reaction of acute myocardial ischemia (MI) in mice, and to explore its action mechanism.</p><p><b>METHODS</b>Forty adult male C57BL/6 mice were randomly divided into a control group, a sham operation group, a model group and an EA group, 10 mice in each one. The model was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 mA of intensity and 2 Hz /100 Hz of frequency; EA was given 30 min per treatment, once a day for totally 5 days. The mice in the control group and model group were treated with immobilization and no EA was given. The mice in the sham operation group were not treated with ligating at the left anterior descending branch of coronary artery, but the remaining procedure was identical to the model group. The electrocardiogram was recorded and △ST was calculated to evaluate the model. TTC and HE staining methods were applied to evaluate the infarct size and pathologic change of myocardial tissue, respectively. Western blot method was applied to test the protein expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-κB p65 (NF-κB p65), interleukin-1β (IL-1β) and interleukin-8 (IL-8).</p><p><b>RESULTS</b>Compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously after modeling (both <0.01), indicating the MI model was established successfully. The TTC and HE staining results indicated, compared with the sham operation group, the model group had larger infarction size (<0.01), more myocardial fibers injury and inflammatory infiltration; compared with the model group, the infarction size of the EA group was significantly reduced (<0.01), and the myocardial fibers injury and inflammatory infiltration were improved. Compared with the control group, the protein expression levels in the sham operation group were similar (all >0.05); compared with the sham operation group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly increased in the model group (<0.01, <0.05); compared with the model group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly reduced in the EA group (all <0.05).</p><p><b>CONCLUSION</b>EA might reduce the protein expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 in cardiac muscle tissue to inhibit inflammatory reaction and achieve myocardial protective effect in mice with acute myocardial ischemia.</p>
Subject(s)
Animals , Male , Mice , Electroacupuncture , Inflammation , Therapeutics , Interleukin-1beta , Metabolism , Interleukin-8 , Metabolism , Mice, Inbred C57BL , Myocardial Ischemia , Therapeutics , Myocardium , Pathology , Random Allocation , Transcription Factor RelA , Metabolism , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the expression of parahippocampal factor-κB p 65 mRNA (NF-κB p 65 mRNA), IκB mRNA, interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in rats with cerebral ischemia (CI), so as to investigate its molecular mechanisms underlying improving CI by reducing inflammatory response. METHODS: A total of 64 SD rats were randomized into normal control, model, medication and scalp-acupuncture groups, with 16 rats in each group. The focal CI model was established by middle cerebral artery occlusion (MCAO). Intraperitoneal injection of Pyrrolidine Dithiocarbamate (100 mg•kg－1•d－1) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), followed by twirling the needles at 200 cycles/min for 1 min, once again every 10 min during 30 min's needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－5 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schäbitz's (2004) methods, respectively. The expression levels of NF-κB p 65 mRNA and IκB mRNA in the parahippocampus gyrus tissue were detected by fluorescence quantitative reverse transcription-PCR, and IL-1 β and TNF-α proteins in the parahippocampus gyrus tissue were detected by immunohistochemistry. RESULTS: After modeling, the neurologic deficit and neurological function scores and the expression levels of NF-κB p 65 mRNA, IL-1 β and TNF-α in the parahip-pocampus were significantly increased in the model group than in the normal group (P<0.01), while the expression of IκB mRNA was considerably down-regulated (P<0.01). Following treatment intervention, the neurologic deficit and neurological function scores as well as NF-κB p 65 mRNA, and IL-1 β and TNF-α protein expression were significantly decreased in both scalp-acupuncture and medication groups compared with the model group (P<0.05, P<0.01), and the decreased expression of IκB mRNA was obviously increased (P<0.05)．. CONCLUSION: Scalp-acupuncture can improve neurologic function in cerebral ischemic rats, which is related with its effects in up-regulating the expression of IκB to inhibit the dissociation of NF-κB, then decreasing the expression of IL-1 β and TNF-α (reducing inflammatory response) in the parahippocampal gyrus tissue.