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Objective: In this study, the clinical application and efficacy of three different methods for placing and repositioning patients in the lithotomy position over the bed using stirrups were evaluated. Methods: A total of 240 surgical patients who underwent surgery in Chongqing Traditional Chinese Medicine Hospital between July and November 2022 were selected as study participants. Using envelopes, they were randomly divided into three groups of 80 cases each using a randomization method. The groups included the traditional over-bed method, the postural trolley-assisted over-bed method, and the direct over-bed method. Using the Kruskal-Wallis rank-sum test, analysis of variance, and multiple linear regression equations, the placement time, over-bed repositioning time, and total time of the three methods for placing and repositioning in the lithotomy position supported by stirrups were analyzed statistically. In addition, we investigated and examined the satisfaction of nurses and doctors with the aforementioned techniques. Results: The placement time, repositioning time, and total time were significantly higher for the traditional over-bed method than for the postural trolley-assisted over-bed method and the direct over-bed method (both P < 0.01). However, there was no statistically significant difference between the postural trolley-assisted over-bed method and the direct over-bed method (P > 0.05). Nurses and doctors reported significantly higher satisfaction with the postural trolley-assisted over-bed method and the direct over-bed method compared to the traditional over-bed method (both P < 0.01). In addition, nurses were more satisfied with the direct over-bed method than the postural trolley-assisted over-bed method (P < 0.05). Conclusion: The results of this study demonstrate that the direct over-bed method is preferred for positioning and repositioning patients in the lithotomy position with the support of stirrups.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.
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Artrite Reumatoide/tratamento farmacológico , Dieta Hiperlipídica/métodos , Células Endoteliais/metabolismo , Glucosídeos/uso terapêutico , Interleucina-17/metabolismo , Monoterpenos/uso terapêutico , Vasculite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Glucosídeos/farmacologia , Humanos , Masculino , Monoterpenos/farmacologia , Ratos , Transdução de SinaisRESUMO
Infantile cholestatic hepatopathy (ICH) is a clinical syndrome characterized by the accumulation of cytotoxic bile acids in infancy, leading to serious liver cirrhosis or liver failure. The aetiology of ICH is complicated and some of them is unknown. Regardless of the aetiology, the finial pathology of ICH is hepatocyte apoptosis caused by severe and persistent cholestasis. It is already known that activation of calcium-sensing receptor (CaSR) could lead to the apoptosis of cardiomyocytes. However, the mechanism by CaSR-mediated cholestasis-related hepatocyte apoptosis is not fully understood. Li-Dan-He-Ji (LDHJ), a Traditional Chinese Medicine prescription, was developed to treat ICH. Another aim of this study was to investigate the possible mechanisms of LDHJ in cholestasis-related hepatocyte apoptosis. Using the primary hepatocytes, we first investigated the molecular mechanism of CaSR-mediated hepatocyte apoptosis in cholestasis. Then we prepared LDHJ granules and used ultra-high-performance liquid chromatography to identify the predominant drugs; confirmed the stability of the main substances; and for cell experiments screened forsythoside-A, emodin and chlorogenic acid as the three active substances of LDHJ granules. In the young rats with ANIT-induced intrahepatic cholestasis and the primary hepatocytes with TCDC-induced cholestasis-related hepatocyte apoptosis, the levels of liver injury and cholestasis-related biomarkers, calcium-sensing receptor (CaSR), hepatocyte apoptosis, Bax/Bcl-2 ratio, Cytochrome-C, caspase-3, phosphorylated-c-Jun NH2-terminal kinase (p-JNK)/JNK, and p-P38/P38 were all increased, while the levels of p-extracellular signal-regulated kinase (p-ERK)/ERK were decreased. However, LDHJ granules and its three active substances effectively reversed these changes. Furthermore, the three active substances reduced the increases in the intracellular calcium concentration ([Ca2+]i) and ROS levels and attenuated the dissipation of the mitochondria membrane potential in the TCDC-induced primary hepatocytes. The opposite results were obtained from the TCDC-induced primary hepatocytes treated with an agonist of CaSR (GdCl3) plus forsythoside-A, emodin or chlorogenic acid. Based on the results from in vivo and in vitro studies, LDHJ functions as an antagonist of CaSR to regulate hepatocyte apoptosis in cholestasis through the mitochondrial pathway and mitogen-activated protein kinase pathway.
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The aim of this paper was to investigate the mechanism and effect of psoralen and isopsoralen in the treatment of lipid accumulation in LO2 cells. Human LO2 cells nonalcoholic fatty liver models were established by using palmitic acid( PA). Then psoralen and isopsoralen were administered for intervention. Intracellular triglyceride( TG) and total cholesterol( TC) content,the cell supernatant alanine aminotransferase( ALT) and aspartate aminotransferase( AST) levels were determined by enzyme method. Cell supernatant proinflammatory cytokines( IL-6,TNF-α) and chemokines( IL-8,MCP-1) were determined by ELISA method. Western blot method was conducted to detect the protein expression of intracellular nuclear factor( NF-κB) p65 phosphorylation( p-p65),nonphosphorylated protein( p65),and transforming factor TGF-ß1. Result showed that as compared with the model group,intracellular TG and TC levels,the cell supernatant ALT and AST levels,proinflammatory cytokines and chemokines were decreased( P < 0. 01,P <0. 05); the p-p65/p65 ratio and TGF-ß1 protein expression were also significantly decreased( P< 0. 01,P< 0. 05) in psoralen intervention group. As compared with the model cells,intracellular TG content had no significant changes,but all the other indexes were reduced( P<0. 01,P<0. 05) in the cells of isopsoralen intervention group. Psoralen exhibited better effect than isopsoralen( P< 0. 01,P<0. 05). It is concluded that psoralen could improve the adipogenesis of LO2 cells induced by PA; both psoralen and isopsoralen are effective in ameliorating LO2 cells injury induced by PA,reducing inflammation via inhibiting the activation of NF-κB and down-regulating the expression of TGF-ß1.
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Ficusina/farmacologia , Furocumarinas/farmacologia , Metabolismo dos Lipídeos , NF-kappa B/metabolismo , Linhagem Celular , Humanos , Hepatopatia Gordurosa não AlcoólicaRESUMO
To investigate the mechanism and effect of Psoralea corylifolia(PC) in the treatment of NAFLD in juvenal mice. The NAFLD model in juvenal mice was established by feeding high-fat diet. Then PC herbal granules (at low and high dose) were administered for 5 weeks. Blood glucose (FBG, PG-1 h/2 h), blood lipid (TC, TG, HDL-C, LDL-C), fasting insulin, liver function (ALT, AST) were examined. HOMA-IR was calculated. Hepatic histological changes were observed. The content of TG, inflammatory factor (TNF-α, IL-8) and protein expressions of CD44, NF-κB p65, p-NF-κB p65 in hepatic tissues were determined. The ratio of p-NF-κB p65 to NF-κB p65 (p-p65/p65) was calculated. The result showed that compared with the model group, both PC treatment groups showed reduction in hepatic steatosis, inflammatory cell infiltration and fibroplasia in portal area. HOMA-IR, ALT, AST, FBG, PG-2 h, TC, TG, LDL-C concentrations and hepatic TG content were also significantly decreased, with the reduction of TNF-α, IL-8 contents, CD44 expression and p-p65/p65 ratio in hepatic tissues (P<0.01). High-dose PC group had a better effect than low-dose group (P<0.01, P<0.05). In conclusion, PC is effective in treating hepatic injury, glucolipid metabolism disturbances and fibrosis in juvenal NAFLD mice. The mechanism may be related to inhibition of inflammation and down-regulation of the activation of hepatic NF-κB.
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Medicamentos de Ervas Chinesas/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Psoralea/química , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Dieta Hiperlipídica , Interleucina-8/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 µM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway.
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Antineoplásicos Fitogênicos/farmacologia , Euphorbia/química , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Células HCT116 , Humanos , Células KB , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/químicaRESUMO
Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL.
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Venenos de Abelha/uso terapêutico , Meliteno/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose/efeitos dos fármacos , Venenos de Abelha/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Humanos , Imunoterapia , Meliteno/genética , Meliteno/farmacologia , Invasividade Neoplásica , Neoplasias/patologiaRESUMO
OBJECTIVE: To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. METHODS: A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. RESULTS: Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. CONCLUSIONS: Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.
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Colestase Intra-Hepática/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Emodina/administração & dosagem , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Feminino , Humanos , Fígado/enzimologia , Fígado/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In this study, we investigated the in vitro antifungal effects of itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine (TET) against 23 clinical isolates of A. fumigatus using a chequerboard microdilution method. The dynamic antifungal effects of TET with ITR/VRC against A. fumigatus were assessed in vivo using time-kill curves following systemic infection of mice with A. fumigatus. After treatment, efflux pump activity was determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET, ITR MICs were reduced from 0.125-32 to 0.0625-2 µg ml(-1), and TET MICs were reduced from 256-512 to 8-64 µg ml(-1). When VRC was combined with TET, VRC MICs were reduced from 0.125-2 to 0.03125-0.5 µg ml(-1), and TET MICs were reduced from 256-512 to 8-256 µg ml(-1). Time-kill curves revealed that A. fumigatus viability was reduced after treatment with ITR/VRC combined with TET versus ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival and reduced kidney and brain tissue burdens versus ITR/VRC alone (P < 0.05). Moreover, TET inhibited R6G efflux of A. fumigatus. Thus, in vitro and in vivo, TET acted synergistically with ITR/VRC against A. fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump.
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Aspergilose/tratamento farmacológico , Aspergillus fumigatus/efeitos dos fármacos , Benzilisoquinolinas/uso terapêutico , Itraconazol/uso terapêutico , Voriconazol/uso terapêutico , Animais , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Aspergilose/microbiologia , Benzilisoquinolinas/administração & dosagem , Ciclofosfamida/toxicidade , Quimioterapia Combinada , Hospedeiro Imunocomprometido , Imunossupressores/toxicidade , Itraconazol/administração & dosagem , Camundongos , Testes de Sensibilidade Microbiana , Voriconazol/administração & dosagemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional and local medicinal knowledge would be useful for finding pharmaceutical resources. Ethnopharmacological methods, especially quantitative analysis could help us to pre-screen herbs in field studies. "Using different plants as the same herb" is common in both traditional and local medicinal systems in China. In terms of medicine safety, it is not best choice, for it would lead to difficulty in controlling the quality, safety and efficacy of herbs. However, from the perspective of finding new resources for pharmaceutical industry, it would be beneficial. The usage of Huang-lian is one of the typical examples of "using different plants as the same herb". According to the previous Phytochemical and Pharmacological studies, berberine is the common effective compound of most of the species used as Huang-lian. Recently, berberine and other effective compounds of Huang-lian have gained much more attention and will become more popular in both medicinal researches and pharmaceutical industry. In our preliminary field work, we found that dozens of plant species might be used as Huang-lian by local people in Northwest Yunnan, an area well known by its rich biodiversity and culture diversity. These herbs might have potential value for pharmaceutical industry, for example, it could be used as the new resources to extract berberine and other effective compounds. Due to this, it is very necessary to collect, identify, document, and analyze the herbs used as Huang-lian in NW Yunnan. In the present study, we focused on that how to use traditional and local medicinal knowledge to find resources for pharmaceutical industry. MATERIAL AND METHODS: In the field work, interviews and participative observation were used. In the quantitative analysis of the local knowledge, Informant consensus factor (Fic), Use value (UV) and Relative frequency of citation (RFC) were used. RESULTS AND DISCUSSION: A total of 230 key informants were interviewed and 29 plant species belonging to 8 families and 11 genera used as Huang-lian were collected in the study area. Diarrhoea had the highest value of Fic.xiana had the highest value of UV and RFC. The main effective compounds of most of these species were related to the protoberberine group of isoquinoline alkaloids, e.g. berberine, jatrorrhizin and palmatine, according to the previous phytochemical studies. CONCLUSION: The range of sources of Huang-lian were very wide in NW Yunnan. Treating diarrhoea was the most common use of these species, most of which contained berberine. Based on the results of quantitative analysis, M. duclouxiana may had the greatest potential to future uses, e.g. as a resource for pharmaceutical industry. In the present study, we did not discuss whether the herbs used as Huang-lian could replace the standard Huang-lian in traditional or local medicine or not, and we just wanted to explore how this phenomenon could be used to find new resources for pharmaceutical industry.
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Medicina Tradicional/métodos , Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , China , Etnofarmacologia , Humanos , Inquéritos e QuestionáriosRESUMO
Pure compounds isolated from complex natural plants are important for drug discovery. This study describes a novel two-dimensional hyphenation of counter-current chromatography and high-performance liquid chromatography (2D CCC×HPLC) with heart-cutting and stop-and-go techniques for preparative isolation of multiple targets components from Peucedanum praeruptorum Dunn (Umbelliferae) crude extracts in a single step. The CCC and HPLC were hyphenated via a 4-port valve equipped at the post-end of the CCC column, to heart cut the impure fractions to the 2nd dimensional HPLC for further separation. Furthermore, the stop-and-go flow scheme was applied in the 1st dimensional CCC to fit with the time constraints of the 2nd dimensional preparative HPLC. Last but not least, an optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds, resulting in the improvement of the CCC column efficiency. By taking the advantages of this rationally designed system, sixteen coumarins were isolated from 1.0g of P. praeruptorum crude extract, with HPLC purity from 90.1% to 99.5%, in a single 2D separation run. More interestingly, two minor linear coumarins and one angular coumarin were isolated from P. praeruptorum Dunn for the first time. As far as we known, this is the first report on the combination of heart-cutting technique and stop-and-go protocol in 2D CCC×HPLC system, by which good separations on comprehensive matrix were achieved. We expect that this approach may have broad applications for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.
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Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/isolamento & purificação , Distribuição Contracorrente/métodos , Cromatografia Líquida de Alta Pressão/instrumentação , Extratos Vegetais/química , Solventes/químicaRESUMO
The aim of this study was to investigate the expression of G proteins in fibroblast-like synoviocytes (FLSs) from rats with collagen-induced arthritis (CIA) and to determine the effect of total glucosides of paeony (TGP). CIA rats were induced with chicken type II collagen (CCII) in Freund's complete adjuvant. The rats with experimental arthritis were randomly separated into five groups and then treated with TGP (25, 50, and 100mg/kg) from days 14 to 35 after immunization. The secondary inflammatory reactions were evaluated through the polyarthritis index and histopathological changes. The level of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The FLS proliferation response was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The toxin-catalyzed ADP-ribosylation of G proteins was performed through autoradiography. The results show that TGP (25, 50, and 100mg/kg) significantly decreased the arthritis scores of CIA rats and improved the histopathological changes. TGP inhibited the proliferation of FLSs and increased the level of cAMP. Moreover, the FLS proliferation and the level of Gαi expression were significantly increased, but the level of Gαs expression was decreased after stimulation with IL-1ß (10ng/ml) in vitro. TGP (12.5 and 62.5µg/ml) significantly inhibited the FLS proliferation and regulated the balance between Gαi and Gαs. These results demonstrate that TGP may exert its anti-inflammatory effects through the suppression of FLS proliferation, which may be associated with its ability to regulate the balance of G proteins. Thus, TGP may have potential as a therapeutic agent for the treatment of rheumatoid arthritis.
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Anti-Inflamatórios/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Proteínas de Ligação ao GTP/metabolismo , Glucosídeos/uso terapêutico , Paeonia , Fitoterapia , Extratos Vegetais/administração & dosagem , Membrana Sinovial/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Galinhas , Colágeno Tipo II/imunologia , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Fibroblastos/patologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Paeoniflorin (Pae) is a monoterpene glucoside and the main component of the total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora. Its anti-inflammatory effect is associated with regulating G-protein-coupled receptors (GPCRs) signaling. The aim of this study was to explore the expression change of G-protein-coupled receptor kinase 2 (GRK2) in fibroblast-like synoviocytes (FLS) and the effect of Pae. Pae was obtained and purified from the roots of Paeonia lactiflora. We investigated the expression of GRK2 in synovium during the inflammatory process and assessed the effects of a specific GRK2 inhibitor and Pae on proliferation, cAMP level, and protein kinase A (PKA) activity of FLS in vitro. Additionally, the effect of Pae on GRK2 expression in FLS was detected in vitro. Expression of GRK2 in synovium from CIA rats increased during the inflammatory process. The specific GRK2 inhibitor suppressed proliferation and increased the cAMP level as well as PKA activity of FLS, and Pae had the same effects. Furthermore, Pae decreased GRK2 expression in FLS in vitro. Our results indicate that a chronic inflammatory process in CIA induces upregulation of GRK2 expression in FLS, and Pae can reverse this change, which might be one of the important mechanisms for Pae regulating GPCRs signaling and suppressing the proliferation of FLS in CIA.
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Artrite Experimental/tratamento farmacológico , Benzoatos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Glucosídeos/farmacologia , Fitoterapia , Membrana Sinovial/enzimologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Proliferação de Células/efeitos dos fármacos , Doença Crônica , Colágeno , Inibidores Enzimáticos/metabolismo , Fibroblastos/enzimologia , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Humanos , Masculino , Monoterpenos , Paeonia/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (Pae) is extracted from the root of paeonia lactiflora which have attracted attention for anti-rheumatic and immune modulating properties. AIM OF THE STUDY: To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen-induced arthritis (CIA). MATERIALS AND METHODS: CIA rats were randomly separated into different groups and treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt and mTOR. RESULTS: In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF-R, PI3K, p-Akt and mTOR. CONCLUSION: PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats. Pae had therapeutic effects on rats with CIA. These effects might be relative to regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the antibodies production further.
Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Autoanticorpos/sangue , Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/imunologia , Benzoatos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Glucosídeos/farmacologia , Paeonia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Articulação do Tornozelo/efeitos dos fármacos , Articulação do Tornozelo/enzimologia , Articulação do Tornozelo/imunologia , Articulação do Tornozelo/patologia , Anti-Inflamatórios/isolamento & purificação , Artrite Experimental/enzimologia , Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/enzimologia , Linfócitos B/imunologia , Benzoatos/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Glucosídeos/isolamento & purificação , Masculino , Monoterpenos , Paeonia/química , Fosforilação , Fitoterapia , Raízes de Plantas , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/enzimologia , Baço/imunologia , Baço/patologia , Fatores de TempoRESUMO
The transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig), a recombinant fusion protein that modulates B and T cells activation by binding and neutralizing B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), has been shown to have a therapeutic effects on autoimmune disorders. The objective of this study was to investigate immunoregulatory efficacy of TACI-Ig on helper T (Th) cells in mesenteric lymph node (MLN) of adjuvant-induced arthritis (AA) in rats. The levels of BLyS, APRIL, interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor beta (TGF)-ß1, and IL-17 were measured by enzyme-linked immunosorbent assay. The localization and expression of TACI, B-cell maturation antigen (BCMA) and B cell activating factor-receptor (BAFF-R) were investigated by immunohistochemistry and western blotting analysis in MLN. Administration of TACI-Ig significantly reduced histological changes, along with decreased Th1 and Th17-cell cytokines and increased CD4(+)CD25(+)FOXP3(+) regulatory T cell (Treg) and Th2-cell cytokines in MLN of AA rats. The levels of BLyS and APRIL were decreased in MLN homogenate of AA rats after treatment with TACI-Ig. TACI-Ig inhibited TACI and BCMA expression, and increased BAFF-R expression in MLN with AA rats. Taken together, BLyS/APRIL-receptors signaling are important not only for B cell function but for T cell-mediated immune responses. TACI-Ig might exert its anti-inflammatory and immunoregulatory effects through inducing immune balance of Th1/Th2 and Treg/Th17 in peripheral MLN. The mechanisms of TACI-Ig on BLyS/APRIL-receptors-dependent signaling in MLN lymphocytes may play key roles in the pathogenesis of autoimmune disorders.
Assuntos
Artrite Experimental/imunologia , Linfonodos/imunologia , Receptores do Fator de Necrose Tumoral/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Artrite Experimental/tratamento farmacológico , Receptor do Fator Ativador de Células B/imunologia , Antígeno de Maturação de Linfócitos B/imunologia , Citocinas/análise , Citocinas/imunologia , Linfonodos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Resultado do Tratamento , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologiaRESUMO
AIM OF THE STUDY: To investigate the expression of ß-arrestins in fibroblast-like synoviocytes (FLS) from collagen-induced arthritis (CIA) rats and the effect of total glucosides of paeony (TGP). MATERIALS AND METHODS: TGP and glucosides of tripterygium wilfordii (GTW) were intragastriclly administrated to collagen-induced arthritis (CIA) rats after immunization. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index and histopathological changes. Antibodies to type II collagen (CII) were determined by enzyme-linked immunosorbent assay (ELISA). Synoviocyte proliferations were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of ß-arrestins in synoviocytes from CIA rats was measured by western blot. RESULTS: The administration of TGP (25, 50, 100 mg/kg) depressed hind paw swelling and decreased the arthritis scores of CIA rats. TGP improved the pathologic manifestations of CIA. Serum anti-CII antibodies level increased significantly in CIA rats, while TGP had no effect on it. Fibroblast-like synoviocytes (FLS) proliferation was inhibited by TGP (50, 100 mg/kg). On d14, d28 after immunization, ß-arrestins expression greatly up-regulated in synoviocytes from CIA rats and then returned to baseline levels on d42 after immunization. TGP (50, 100 mg/kg) significantly reduced the expression of ß-arrestins. CONCLUSION: An inflammatory process in vivo induces an up-regulation of ß-arrestins in synoviocytes from CIA rats while TGP can inhibit this change, which might be one of the important mechanisms for TGP to produce a marked therapeutic effect on RA.
Assuntos
Arrestinas/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Glucosídeos/uso terapêutico , Paeonia , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Autoanticorpos/sangue , Queixo , Colágeno Tipo II/imunologia , Etnofarmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Masculino , Paeonia/química , Fitoterapia , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Regulação para Cima/efeitos dos fármacos , beta-ArrestinasRESUMO
OBJECTIVE: To observe the clinical efficacy of self-formulated Xingchang Decoction (XCD) in treating slow-transit constipation (STC) and the dynamical parameters of colonic motility during XCD treatment. METHODS: One hundred and eighteen patients with STC were randomly assigned to the treatment group and the control group, 59 in each group. The treatment group was treated with XCD, and the control group was treated with mosapride, an intestinal energetic agent. The therapeutic course for both groups was 30 days. The 72-h colonic transition test was conducted and the symptom scores were observed before and after treatment; the adverse reaction rate and clinical efficacy were calculated after treatment; and the recurrence rate in one year was followed-up. RESULTS: Symptom scores were significantly improved in the treatment group after treatment, with the improvement significantly superior to that in the control group (P < 0.01). The cure rate and the total effective rate were 76.27% and 93.22% in the treatment group respectively, while they were 47.45% and 72.87% in the control group, showing significant difference between the two groups (P < 0.01). Besides, the 1-year recurrence rate was significantly lower (chi2 = 10.40, P = 0.001) and the improvement of colonic motor function was more in the treatment group than those in the control group (P < 0.01). Only low incidence (5.08% in the treatment group and 8.47% in the control group) of mild gastrointestinal reactions was shown, which caused no influence on the treatment. CONCLUSION: XCD could effectively improve the motility of the digestive tract, and it is effective and safe for the treatment of STC.
Assuntos
Constipação Intestinal/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Trânsito Gastrointestinal/efeitos dos fármacos , Benzamidas/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Morfolinas/uso terapêuticoRESUMO
OBJECTIVE: To study the inhibitive effects of an effective section of a prescription of traditional Chinese medicine (TCM-ES) on influenza virus A FM1 strain in vitro. METHODS: The experiments were performed by microcytopathic-inhibiting-assay, Neutral Red stain and inhibiting plaque-forming units (PFU) test on MDCK cell strain. By means of observing the cytopathic effects (CPE), measuring the absorbance [D(lambda)] and counting the PFU, according to Reed-Muench assay, the TCM-ES's effective dosage of 50 percentage (EC50) and treatment index (TI) to FM1 were calculated. The inhibiting dose of 50 percentage of PFU (IC50) was also figured up. RESULTS: By CPE assay, TCM-ES'S EC50, MTC and TI to 100TCID50 FM1 strain infection were (300 +/- 18.3) mg/L, (75 +/- 6.8) mg/L and (7.1 +/- 0.7), respectively; Whereas, ribavirin's EC50, MTC and TI was (52.3 +/- 10.1) mg/L, (25 +/- 4.1) mg/L and (20.8 +/- 5.1), respectively. By Neutral Red stain assay,TCM-ES's IC50 and TI was (285.0 +/- 19.2) mg/L and (7.2 +/- 0.6), respectively; whereas ribavirin's IC50 and TI was (45.3 +/- 4. 9) mg/L and (21.2 +/- 3.1), respectively. By reducing PFU assay, the IC50 of TCM-ES and ribavirin was 300 mg/L and 50 mg/L, respectively. All the results above were almost consistent with each other (P > 0.05). CONCLUSIONS: TCM-ES assumes antiviral action on IFV-FM1 strain in a certain degree in vitro and can rebel intracellular virus. But it is worse than the positive control medicine of ribavirin and is worthy of further study.
Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Plantas Medicinais/química , Animais , Antivirais/isolamento & purificação , Células Cultivadas , Cães , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Vírus da Influenza A/fisiologia , Concentração Inibidora 50 , RNA Viral/efeitos dos fármacos , Ribavirina/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
Experiments in rats have shown that chronic visceral hyperalgesia can be relieved by electro-acupuncture, but the efficacy of suspended moxibustion for relieving chronic visceral hyperalgesia is still unclear. The present study aimed to evaluate the effect of suspended moxibustion on rectal sensory thresholds and to analyze its possible mechanisms when treating chronic visceral hypersensitivity rats. Suspended moxibustion was administered once daily to 37-day-old chronic visceral hypersensitivity rats for 7 days. The two acupoints (ST25, bilateral) were simultaneously given suspended moxibustion. Each treatment lasted for 15 min. Rats in treatment of suspended moxibustion was not anesthetized. Untreated chronic visceral hypersensitivity rats and normal rats were used as controls. The abdominal withdrawal reflex was determined during 30-90 min after the first treatment. A 5-cm long segment of distal colon was harvested after seven treatments and 5-hydroxytryptamine concentrations in the colon were assayed by enzyme-linked immunosorbent assay. Abdominal withdrawal reflex scores from the rectus abdominis in response to colorectal distention were increased in rats with chronic visceral hypersensitivity, and the stimulation at strength of 20 mmHg was significantly depressed by suspended moxibustion. Suspended moxibustion increased the pain threshold and restored normal sensitivity by reducing 5-hydroxytryptamine concentrations in the colon of chronic visceral hypersensitivity rats.
Assuntos
Colo/fisiopatologia , Hiperalgesia/fisiopatologia , Hiperalgesia/terapia , Moxibustão/métodos , Serotonina/metabolismo , Fibras Aferentes Viscerais/fisiopatologia , Animais , Animais Recém-Nascidos , Colo/inervação , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Hiperalgesia/metabolismo , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Masculino , Nociceptores/fisiologia , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Reflexo/fisiologia , Serotonina/análise , Resultado do Tratamento , Fibras Aferentes Viscerais/metabolismoRESUMO
To better understand the requirement of light and soil water conditions in the invasion sites of two invasive weeds, Mikania micrantha and Chromolaena odorata, we investigated their structural and physiological traits in response to nine combined treatments of light [full, medium and low irradiance (LI)] and soil water (full, medium and low field water content) conditions in three glasshouses. Under the same light conditions, most variables for both species did not vary significantly among different water treatments. Irrespective of water treatment, both species showed significant decreases in maximum light saturated photosynthetic rate (P (max)), photosynthetic nitrogen-use efficiency, and relative growth rate under LI relative to full irradiance; specific leaf area, however, increased significantly from full to LI though leaf area decreased significantly, indicating that limited light availability under extreme shade was the critical factor restricting the growth of both species. Our results also indicated that M. micrantha performed best under a high light and full soil water combination, while C. odorata was more efficient in growth under a high light and medium soil water combination.