Analgesic effect of Fengshi Qutong Capsules on mice with chronic inflammatory pain caused by complete Freund's adjuvant / 中国中药杂志

The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC) on chronic inflammatory pain in mice, and investigate its effect on p-ERK/COX-2 signal molecular activity. A model of chronic inflammatory pain was induced in mice by complete Freund's adjuvant(CFA). The mice were divided into normal control group, model group, model+FSQTC 0.3, 0.6 and 1.2 g·kg~(-1 )groups, model+positive control drug ibuprofen(IBP, 0.34 mg·kg~(-1)·d~(-1)) group, and normal control+ FSQTC 1.2 g·kg~(-1)group. FSQTC or IBP was given once a day by oral administration. Standard Von Frey fiber was used to evaluate the mechanical pain threshold, and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores. The mechanical pain threshold and cold pain reaction scores were observed before administration and 1, 2, 3, 4, 6 h after administration on the first day, as well as 3 h after administration on the 3 rd to 7 th day. The protein levels of PGE_2, COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay, Western blot, immunohistochemistry and immunofluorescence. The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group. FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score. The effect lasted for 6 h, most significant at 3 h. The effect of ibuprofen was similar to that of the 0.6 g·kg~(-1) dose group. In addition, FSQTC could reduce the abnormally increased protein content of PGE_2, COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group, and the effect was most significant in middle and high dose groups. However, it had no effect on COX-1 in the inflammatory foot and spinal cord of mice. The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice, which may be related to inhibition of p-ERK/COX-2 signaling pathway.

Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygium Glycosides Tablets or combined administration with methotrexate against rheumatoid arthritis / 中国中药杂志

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis / 中国中药杂志

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

Comparative study on chronic multiple organ injury in normal rats caused by high dose of Tripterygium Glycosides Tablets from 6 different manufacturers / 中国中药杂志

The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.

Antidepressant-like effects of albiflorin involved the NO signaling pathway in rats model of chronic restraint stress / 中国天然药物

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg

Effect of Fengshi Qutong Capsule on Collagen-induced Arthritis of Rats / 中国实验方剂学杂志

Objective:To observe the intervention effect of Fengshi Qutong capsule on collagen-induced arthritis (CIA) in rats. Method:SD rats were randomly divided into normal group, model group, low, medium and high-dose Fengshi Qutong capsule groups (0.25, 0.5, 1 g·kg-1·d-1), and methotrexate group(0.2 mg·kg-1·d-1).Except for normal group, the other groups were immunized with type Ⅱ collagen and incomplete Freund's adjuvant to establish a CIA model. On the 1st day after the first immunization, the administration group was given intragastric administration, once a day, for 19 days; on the 8th day after the first immunization, the symptoms of joint swelling and malformation of the rats were observed, and the clinical scores and incidence of arthritis were evaluated. On the 19th day, micro-computed tomography and bone metrology were performed, and histopathological examination of inflammatory joints was performed,andsynovial inflammation,vasospasm, cartilage erosion and bone destruction by pathological severity scores, serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF),matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor kappa B ligand(RANKL)were detected by enzyme linked immunosorbent assay. Result:Fengshi Qutong capsule could improve the symptoms of inflammatory joint redness, swelling and deformity in CIA rats in a dose-dependent manner. Compared with normal group, clinical score and incidence, joint synovial inflammation, vasospasm, cartilage erosion and pathological score of bone destruction in joint group were significantly increased (PPPβ, TNF-α, VEGF, MMP-3 and RANKL in serum were increased (PPPPPPPβ, TNF-α, VEGF, MMP-3 and RANKL were significantly decreased (PPConclusion:Fengshi Qutong capsule can effectively alleviate the clinical symptoms and conditions of experimental rheumatoid arthritis in rats, reduce the incidence, and relieve the histopathology and imaging severity, while inhibiting the inflammatory cytokines.

Effect of Fengshi Qutong Capsules on synovial angiogenesis in rats with type Ⅱ collagen induced arthritis / 中国中药杂志

To observe the effect of Fengshi Qutong Capsules(FSQTC) on angiogenesis of rat aortarings and in knee joint synovium of type Ⅱ collagen-induced arthritis(CIA) rats. The blood vessel of aorta rings of normal SD rats were induced by vascular endothelial growth factor(VEGF) 20 μg·L~(-1 )in vitro, and were treated with FSQTC(0.02, 0.1 and 0.5 μg·L~(-1)) continuously for 9 days. The number, length and area of neovascularization of the vascular ring were measured. SD rats were immunized to establish collagen-induced arthritis. CIA rats were treated with FSQTC(0.25, 0.5, 1 g·kg~(-1)·d~(-1)) and methotrexate(0.2 mg·kg~(-1)·d~(-1)) daily for 19 days. Histopathological examination(HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joint. Immunohistochemistry was performed to observe the expression of platelets-endothelial cell adhesion molecule(CD31), VEGF and VEGF receptor 2(VEGFR_2)in the synovium. Immunofluorescence was performed to observe the expression of CD31 and α smooth muscle actin(αSMA) in synovial membrane.TGF-β, PDGF and VEGFR_2 in serum were detected by enzyme-linked immunosorbent assay. The number, branch length and area of blood vessels of aorta rings were significantly increased induced by VEGF, and FSQTC could significantly reduce the number, branch length and area of blood vessels. Compared with the normal group, the vascular density, CD31 positive expression, CD31~+/αSMA~- immature and total vascular positive expression in the synovial membrane of the model group were significantly increased, and so as VEGF and VEGFR_2 in the synovium. The VEGFR_2, TGF-β and PDGF in sera were also significantly increased in model group. FSQTC reduced the synovial vascular density and inhibited the positive expression of CD31, CD31~+/αSMA~- immature blood vessels and total vascular. FSQTC has no significant effect on CD31~+/αSMA~+mature blood vessels. FSQTC also negatively inhibited the expression of VEGF, VEGFR_2, TGF-β and PDGF in synovial membrane and/or sera. The effect of methotrexate is similar with to the high dose group. Our results demonstrated that FSQTC could inhibit the angiogenesis of synovial tissue in CIA rats and of aortaring in rats, which is related to the reduction of angiogenesis regulatory factor.

Effect of Tripterygium Glycosides Tablets on synovial angiogenesis in rats with type Ⅱ collagen induced arthritis / 中国中药杂志

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.

Effects of Tripterygium Glycosides Tablets from 6 different manufacturers on acute liver injury of normal mice / 中国中药杂志

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.

Clinical symptoms effect of Tripterygium Glycosides Tablets alone or combined with methotrexate in treatment of rheumatoid arthritis: a Meta-analysis / 中国中药杂志

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.

Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis / 中国中药杂志

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

Discussion on safety evaluation and risk control measures of Epimedii Folium / 中国中药杂志

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.

Effect of Fengshi Qutong Capsule on Human Umbilical Vein Endothelial Cells Induced by VEGF / 中国实验方剂学杂志

Objective: To study the effect of Fengshi Qutong capsule on the migration, adhesion, invasion and tube formation of human synovial cells and the phosphorylation and protein expression of vascular endothelial growth factor receptor 2 (VEGFR2). Method: With human umbilical vein endothelial cells (HUVEC) as the research object, low, middle and high-dose Fengshi Qutong capsule(0.02,0.1,0.5 μg·L-1) on HUVEC was determined by methye thiazolye telrazlium (MTT) colorimetric assay for the follow-up experiment. The transwell migration, adhesion and transwell invasion test were used to detect the migration and adhesion of the different concentrations of Fengshi Qutong capsule in HUVEC. The expression of VEGFR2 in HUVEC was detected by Western blot, and Real-time PCR was used to detect the content of VEGFR2 mRNA in cells. Result: Compared with normal group, the proliferation of HUVEC was significantly increased after 24 h and 48 h of VEGF induction (PPP-1 Fengshi Qutong capsule were administered in vitro for 48 h to inhibit HUVEC proliferation activity in a dose-dependent manner (PPPPConclusion: Fengshi Qutong capsule can inhibit the migration, adhesion, invasion and tube formation of HUVEC. This effect may be related to the inhibition of phosphorylation, and protein and mRNA expression level of VEGFR2.

Effect of Fengshi Qutong Capsule on Synovial Akt and MAPK Signaling Pathways in Rheumatoid Arthritis / 中国实验方剂学杂志

Objective:To observe the effect of Fengshi Qutong capsule (FSQTC) on protein kinase B(Akt) and mitogen-activated protein kinase (MAPK) signaling pathways of rheumatoid arthritis (RA). Method:Collagen-induced arthritis (CIA) was induced in SD rats, and the synovial membranes of the knee joints were prepared after 19 days of oral administration of 0.25, 0.5, 1 g·kg-1 FSQTC. MH7A cells were induced by tumor necrosis factor-α (TNF-α, 20 μg·L-1) in vitro, and human umbilical vein endothelial cells (HUVEC) were induced by vascular endothelial growth factor (VEGF). FSQTC (0.02, 0.1, 0.5 μg·L-1) were added to MH7A/HUVEC cells, and then the cells were collected. Proteins of synovial tissue, MH7A and HUVEC cells were extracted, and then were detected the expresstion of p-Akt, p-p38 MAPK, p-extracellular signal-regulated kinase(ERK) and p-Jun n-terminal kinase(JNK) by Western blot. Result:The expression levels of p-Akt, p-p38 MAPK, p-ERK and p-JNK in the synovial membrane of CIA model were significantly increased compared with normal group (P-1·d-1 FSQTC significantly decreased their expression levels (PPα or VEGF were increased (P-1 FSQTC (PPConclusion:FSQTC can down-regulate the abnormal activation of Akt and MAPK signaling pathways in the synovial membrane of CIA rats, fibroblast synovial cells and vascular endothelial cells, which is related to the inhibition of synovial angiogenesis in the treatment of RA.

Effect of Fengshi Qutong Capsule on Function of Human Synovial Cells in Rheumatoid Arthritis Induced by TNF-α / 中国实验方剂学杂志

Objective: To study the effects of Fengshi Qutong capsule (FSQTC) on proliferation, migration, adhesion, invasion and secretion of human synovial cells in rheumatoid arthritis (RA) induced by tumor necrosis factor-α (TNF-α) and explore its mechanism. Method: Human synovial cells (MH7A) in RA patients were induced in vitro by using TNF-α (20 μg·L-1). After treatment with different concentrations of FSQTC (0.02,0.1,0.5 μg·L-1), MTT colorimetric assay, transwell migration, adhesion and invasion tests were used to detect the proliferation, migration, adhesion and invasion of the MH7A, respectively. The expression levels of vascular endothelial growth factor (VEGF) and interleukin-1β (IL-1β) in MH7A supernatant were detected by enzyme linked immunosorbent assay (ELISA). Result: As compared with blank control group, TNF-α (20 μg·L-1) significantly increased the proliferation, migration, adhesion, invasion and secretion of IL-1β and VEGF of MH7A cells (P-1) had no significant effect on proliferation of TNF-α-induced MH7A cells after treatment for 24 hours. After 48 hours of treatment, proliferation of MH7A cells induced by TNF-α was decreased in a concentration-dependent manner (PPPPConclusion: FSQTC can inhibit the proliferation, migration, adhesion, invasion and secretion of IL-1β and VEGF in MH7A cells.

ERα36 is involved in the proliferation promotion and anti-apoptosis effects of icaritin on MG63 cells / 生理学报

The mechanism for icaritin to improve postmenopausal osteoporosis (PMOP) has not been clarified. The aim of this study was to investigate the role of estrogen receptor α36 (ERα36) in the proliferation promotion and anti-apoptosis effects of icaritin on osteoblasts and the underlying mechanism of downstream signal transduction. The ERα36 knockdown human osteosarcoma MG63 cell model was constructed by transfection of shRNA vector. Cell proliferation was detected by CCK-8, the apoptosis was detected by flow cytometry, and the activation of ERK and AKT signaling pathways was detected by Western blot. The results showed that the effects of icaritin on the proliferation and apoptosis of MG63 cells were significantly decreased after ERα36 knockdown, and icaritin could up-regulate the levels of ERK and AKT phosphorylation in MG63 cells, which could be reduced by ERα36 knockdown. The effect of icaritin on the proliferation of MG63 cells was significantly decreased by pretreating the cells with U0126 (an ERK signaling pathway blocker) and LY294002 (an AKT signaling pathway blocker), respectively. Furthermore, anti-apoptotic effect of icaritin on MG63 cells was significantly decreased after the cells were pretreated with U0126, but not with LY294002. These results suggest that icaritin exerts proliferation promotion and anti-apoptosis effects on osteoblasts through ERα36 and its downstream ERK and AKT signaling pathways.

Effects of total flavonoids in Astragali Complanati Semen on liver lipid level and ERα expression on liver in hyperlipidemia rats with kidney-Yang deficiency pattern / 中国中药杂志

Menopausal women appear lipid metabolism disorder with the ovarian function decline and the estrogen levels decreased. Modern clinical usually use estrogen replacement therapy and with long time application with lots of side effect appear. Traditional Chinese medicine has more secure and effective methords,using warming Yang drugs and methods. And the previous study proves the Chinese medicine Astragali Complanati Semen water extraction has a good role in regulation of blood lipids. Because of the liver is the most important organ on regulating metabolism, therefore this study aimed to evaluate the effects of total flavonoids in Astragali Complanati Semen(TFS)on liverlipid level and ERα expressionon liver in hyperlipidemia rats with kidney-Yang deficiency pattern to explore the substance basis and mechanism of Astragali Complanati Semen in regulate lipid effect and clarify traditional Chinese medicine advantages and features. This experiment uses hyperlipidemia rats with kidney-Yang deficiency pattern with bilateral ovariectomized and fed with high fat diet for 6 weeks. And rats of sham operation group and model group rats were intragastrilly(ig) with saline, estrogen group were intragastrilly with estrogen(0.2 mg·kg⁻¹). And three TFS group were intragastrilly with TFS at dose 28.5, 57, 114 mg·kg⁻¹ for 8 weeks. At the same time, TC, TG, LDL-C,HDL-C liver weight, liver index, uterine weight, uterine index, serum estrogen level, FSH levels and liver pathology, liver estrogen receptor expression were detected, weighting and calculating their organ index. The experimental results compared with the model group, TFS 114 mg·kg⁻¹ decreased the level of liver TG (<0.05), TC (<0.001) and LDL-C (<0.001) and increased the level of HDL-C (<0.05). Compared with the model group, estrogen group increased the level of blood serum (<0.001) and decreased the level of FSH (<0.001). In addition, compared with sham operation group,model group decreased the protein expression of ERα（<0.01）. Compared with the model group, estrogen group increased the protein expression of ERα significantly（<0.001）.TFS mid-dose group and TFS high-dose group is increased the protein expression of ERα（<0.01, <0.001）.In a conclusion,Flavonoids is the main active ingredient of Astragali Complanati Semen. The mechanism of it maybe is enhancing the estrogen receptor sensitivity or the number of estrogen receptors, amplifying the signal after the receptor conduction, which could result in lipid-lowering effect.

Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix / 中国中药杂志

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Systematic evaluation for safety of traditional Chinese medicine Areca catechu and its preparations / 中国中药杂志

The authors systemically evaluated and analyzed the safety of Areca catechu from domestic and foreign literatures about the herbal origin, toxicity recorded in ancient/current documents, safety case reports of clinical A. catechu, experimental studies on toxicity in recent years, and differences of safety risk between edible and medicinal A. catechu. Subsequently, they proposed a preliminary summary about the clinical characteristics and potential risk factors of safety related cases of A. catechu and its preparations. According to the authors, although clinical adverse events of A. catechu were fewer and controllable, clinicians shall stillstrictly standardize its application, and rationally combine it with other herbs, while strengthening fundamental and clinical studies related to safety, so as to give better guidance to safety application of A. catechu in clinic.

Comprehensive evaluation and risk control measures of Xanthii Fructus / 中国中药杂志

By retrieving domestic and foreign literatures, the authors provided a systematic review for effects of Xanthii Fructus, toxicity recorded in ancient/current literatures and relevant toxicological experience, and summarized clinical characteristics of clinical cases related to Xanthii Fructus and influencing factors. In addition to liver and kidney injuries as the major side effects of Xanthii Fructus, neurotoxicity and cardio-toxicity of Xanthii Fructus were also common clinical adverse events. However, there have been a few animal experimental studies so far. Oral administration and external application with Xanthii Fructus have often caused skin reactions, even such severe cases as exfoliative dermatitis. The authors suggested standardizing the clinical medication, avoiding to use untreated prescriptions and unprocessed herbs, ensuring the effective and safety use of Xanthii Fructus in strict accordance with the recommended dosage and usage in pharmacopeia, paying attention to the accumulation of safety signals, strengthening studies on toxic substance, toxicity mechanism, and synergy and attenuation effects.