RESUMO
WenDanTang (WDT) is a Chinese herbal formula used to treat various diseases, including neurodegenerative diseases. However, the neuroprotective metabolic pathways and the components involved in this process are not fully understood. In this study, we examined the neuroprotective metabolic pathways of WDT in rat brains using cerebrospinal fluid metabolomics and ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Twelve rats were randomly divided into a WDT (administrated with WDT solution) and a control group. The ultra-high-performance liquid chromatography technique was used to explore the components of the WDT solution and cerebrospinal fluid, and secondary mass spectra of cerebrospinal fluid were used to identify possible brain-incorporating components after WDT. The results of the differential metabolism analysis showed that eight metabolites were typically altered (all p < 0.05). By comparing the secondary mass spectra of the cerebrospinal fluid of rats and WDT solution, two possible brain-incorporating components of WDT, stachydrine and α-methoxyphenylacetic acid, were identified. The data also suggested that WDT affects nucleotide metabolism, glutathione metabolism, and B-vitamin metabolic pathways, the central differential metabolic pathways. These data suggest that WDT protects neurons through its active components, such as stachydrine, and regulates biochemical metabolism to affect the brain's energy metabolism and antioxidant capacity.
Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Espectrometria de Massa com Cromatografia Líquida , Medicamentos de Ervas Chinesas/análiseRESUMO
According to the annual production of plastics worldwide, in 2020 about 370 million tons of plastic were produced in the world. Chemical recycling, particularly pyrolysis of plastic wastes, could be a valuable solution to resolve these problems and provide an alternative pathway to produce "recycled" chemical products for the petrochemical industry. Nevertheless, the pyrolysis oils need a detailed characterization before the upgrading test to re-use them to generate new recycled products. Multidimensional gas chromatography coupled with both low- and high-resolution time-of-flight mass spectrometers was employed for a detailed investigation among and within different chemical classes present in bio-plastic oil. The presence of several isomeric species as well as homologs series did not allow a reliable molecular identification, except for a few compounds that showed both MS similarity >800/1000 and retention index within ±20. Indeed, the identification of several isomeric species was assessed by high-resolution mass spectrometry equipped with photoionization interface. This soft ionization mode was an additional filter in the identification step allowing unambiguous identification of analytes not identified by the standard electron ionization mode at 70 eV. The injection method was also optimized using a central composite design to successfully introduce a wide range of carbon number compounds without discrimination of low/high boiling points.
Assuntos
Plásticos , Pirólise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Óleos de Plantas/química , Compostos OrgânicosRESUMO
Polychlorinated naphthalenes (PCNs) are highly toxic and persistent organic pollutants that can cause adverse effects in the environment and on human health. PCNs have been detected in remote areas because of their long-range transportation. Bees and bee products are commonly used as biomonitors for various pollutants in the environment. However, information on PCNs in apiaries is scarce. The aim of this study was to evaluate the occurrences of PCNs in bees and bee products from apiaries located in different geographical regions of China, and to identify potential pollution sources and assess exposure risks to humans. Our results showed that the average Σ75PCNs concentrations in bees, pollen, and wax were 74.1, 96.3, and 141 pg/g dry weight, respectively. The homologue and congener profiles of PCNs in bees, pollen, and wax were similar, and di- and tri-chlorinated naphthalenes (>60%) were the predominant homologues. The concentrations and distributions of PCNs in bees, pollen, and wax varied among different geographical regions, but their occurrences were correlated with PCN metallurgical sources in China. The health risks of PCNs in pollen were evaluated, and both carcinogenic and non-carcinogenic risks of PCNs exposure to humans through the diet were low.
Assuntos
Monitoramento Ambiental , Poluentes Ambientais , Animais , Humanos , Abelhas , China , Naftalenos/análise , Poluentes Orgânicos Persistentes , Pólen/químicaRESUMO
Polychlorinated naphthalenes (PCNs) were added to the Stockholm Convention list of persistent organic pollutants in 2015. PCNs are mainly unintentionally produced during industrial processes nowadays, and can be widely found in environmental media and foodstuffs. Dietary intake is the primary pathway for human exposure to PCNs. PCNs in different categories of foodstuffs have been reported. However, little information on PCN concentrations in green tea, a popular beverage worldwide is available. In this study, all 75 PCN congener concentrations and distributions in green tea samples (n = 102) from 11 regions in China were determined, and risk assessment of human exposure to PCNs through tea consumption was conducted. The PCN concentrations in all the green tea samples were 3.62-175 pg/g dry weight (mean 36.1 pg/g dry weight). Similar PCN homolog and congener profiles were found in green tea samples from different areas. The dominant PCN homologs in all of the green tea samples were di-CNs, tetra-CNs, and tri-CNs. No direct relationships were found between PCN emission sources and PCN concentrations in the green tea samples. The brewing technique could affect the PCN concentrations and homolog profiles in tea leaves. PCNs in green tea from China were found to pose little risk to humans.
Assuntos
Monitoramento Ambiental , Naftalenos , Humanos , China , Naftalenos/análise , Poluentes Orgânicos Persistentes , Medição de Risco , CháRESUMO
Coffee, one of the most popular beverages in the world, attracts consumers by its rich aroma and the stimulating effect of caffeine. Increasing consumers prefer decaffeinated coffee to regular coffee due to health concerns. There are some main decaffeination methods commonly used by commercial coffee producers for decades. However, a certain amount of the aroma precursors can be removed together with caffeine, which could cause a thin taste of decaffeinated coffee. To understand the difference between regular and decaffeinated coffee from the volatile composition point of view, headspace solid-phase microextraction two-dimensional gas chromatography time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was employed to examine the headspace volatiles of eight pairs of regular and decaffeinated coffees in this study. Using the key aroma-related volatiles, decaffeinated coffee was significantly separated from regular coffee by principal component analysis (PCA). Using feature-selection tools (univariate analysis: t-test and multivariate analysis: partial least squares-discriminant analysis (PLS-DA)), a group of pyrazines was observed to be significantly different between regular coffee and decaffeinated coffee. Pyrazines were more enriched in the regular coffee, which was due to the reduction of sucrose during the decaffeination process. The reduction of pyrazines led to a lack of nutty, roasted, chocolate, earthy, and musty aroma in the decaffeinated coffee. For the non-targeted analysis, the random forest (RF) classification algorithm was used to select the most important features that could enable a distinct classification between the two coffee types. In total, 20 discriminatory features were identified. The results suggested that pyrazine-derived compounds were a strong marker for the regular coffee group whereas furan-derived compounds were a strong marker for the decaffeinated coffee samples.
Assuntos
Café , Microextração em Fase Sólida , Cafeína , Quimiometria , Aprendizado de MáquinaRESUMO
BACKGROUND: This study aimed to detect the effect of angiotensin receptor 1 (AT1) knock out (KO) on spermatogenesis and hypothalamic-pituitary-gonadal (HPG) axis hormone expression. METHODS: Normal C57BL/6 male mice were used as control group or treated with angiotensin receptor blocker, in addition heterozygous ± AT1KO mice were generated. After caged at a ratio of 2 to 1 with females, pregnancy rates of female mice were determined by detection of vaginal plugs. Deformity rate of spermatozoa was evaluated by eosin staining and morphology evaluation. The AT1 mRNA expression in the testes of male ± AT1KO mice was detected by quantitative real-time polymerase chain reaction (QRT-PCR). Serum GnRH level was determined by ELISA. RESULTS: Compared to control, ± AT1KO mice showed reduced expression of AT1 in testes, pituitary and hypothalamus. In addition, decreased level of GnRH, but not follicle stimulating hormone (FSH) or luteinizing hormone (LH), in ± AT1KO mice was detected. Treatment with angiotensin receptor blocker (ARB) did not have significant effects on HPG hormones. ± AT1KO mice exhibited male infertility and significant abnormality of sperm morphology. CONCLUSION: Reduced AT1 knockout resulted in male infertility, potentially by inducing abnormal spermatogenesis. Both testis and HPG axis signaling may be involved.
Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Infertilidade Masculina/genética , Receptor Tipo 1 de Angiotensina/genética , Espermatogênese/genética , Testículo/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Hormônio Liberador de Gonadotropina/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Infertilidade Masculina/metabolismo , Losartan/farmacologia , Masculino , Camundongos , Camundongos Knockout , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacosRESUMO
INTRODUCTION: Severe inflammatory response leads to poor prognosis of acute lung injury (ALI), the role of gypenosides (GPs) on ALI is not fully clear. The study aimed at investigating the effects of GPs on ALI. METHODS: We firstly established LPS-induced ALI mice model. Then, we tested whether GPs contributed to alleviate inflammatory response and lung injury of ALI in vivo. In order to identify specific mechanisms of the phenomenon, we conducted a bioinformatic analysis of LPS-induced ALI mice based on GEO database to identify hub differentially expressed genes (DEGs). PPI network of the DEGs was used to find hub-genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted based on the DAVID database to identify which pathways the genes enriched. Then, we tested whether GPs inhibited lung injury and inflammatory response via the enriched pathways. We also tested whether GPs inhibited the apoptosis of endothelial and epithelial cells secondary to severe inflammation. RESULTS: We found GPs significantly alleviated lung injury and improved the survival rate of LPS-induced ALI mice in vivo. Bioinformatic analysis identified 20 hub-genes from DEGs, they were mainly enriched in NF-κB and TNF-α pathways. GPs could reduce the lung injury and inflammatory response via inhibiting NF-κB and TNF-α pathways in vivo. Our results indicated that GPs also inhibited inflammatory response of epithelial and endothelial cells via NF-κB and TNF-α pathways in vitro. Severe inflammatory response could also lead to apoptosis of endothelial and epithelial cells. Our results indicated that GPs effectively inhibited the apoptosis of endothelial and epithelial cells. CONCLUSION: Our study suggested GPs contributed to alleviated lung injury in vivo and inhibited inflammation and apoptosis of endothelial and epithelial cells in vitro, providing novel strategies for the prevention and therapy for ALI.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Biologia Computacional , Inflamação/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Gynostemma/química , Humanos , Inflamação/patologia , Lipopolissacarídeos/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Topical timolol and 595-nm pulsed dye laser (PDL) are both widely used in the treatment of superficial infantile hemangiomas (IH). However, to date, there is no reliable study comparing the therapeutic outcomes between the two treatment options. We designed the present study to evaluate and compare the efficacy and safety of timolol cream and PDL in the treatment of superficial proliferating IH. Twenty-one patients with superficial IH were included in the study. Each lesion was divided into two regions; one part was treated with 0.5% topical timolol cream four times daily, and the other part was treated monthly with PDL. Both treatments were continued for 2-6 months. Five independent and blinded assessors were asked to judge the results in both the topical timolol-treated and PDL-treated parts by comparing photographs taken before and after treatment. Both treatments resulted in significant clinical improvements after 3.39 sessions in the 2-month follow up. The average visual evaluation showed that PDL had significantly better results than topical timolol (6.55 ± 2.26 to 4.98 ± 2.92, P < 0.01). No patients experienced permanent side-effects during the treatment. Our short-term study revealed that PDL had better results compared with topical timolol cream application in the treatment of superficial proliferating IH. Further studies with longer follow-up time and larger sample size are required to validate our findings.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Hemangioma/radioterapia , Lasers de Corante/uso terapêutico , Timolol/administração & dosagem , Administração Cutânea , Antagonistas Adrenérgicos beta/efeitos adversos , Feminino , Humanos , Lactente , Terapia com Luz de Baixa Intensidade , Masculino , Projetos Piloto , Estudos Prospectivos , Timolol/efeitos adversosRESUMO
RATIONALE: The oxygen exchange fraction between soil H(2)O and N(2)O precursors differs in soils depending on the responsible N(2)O-producing process: nitrification or denitrification. This study investigated the O-exchange between soil H(2)O and N(2)O precursors in a green tea field with high N(2)O emissions. METHODS: The rainwater δ(18)O value was measured using cavity ring-down spectrometry (CRDS) and compared with that of soil water collected under the tea plant canopy and between tea plant rows. The intramolecular (15)N site preference in (ß) N(α) NO (SP = δ(15)N(α) - δ(15)N(ß)) was determined after measuring the δ(15)N(α) and δ(15)N(bulk) values using gas chromatography/isotope ratio mass spectrometry (GC/IRMS), and the δ(18) O values of N(2)O and NO(3)(-) were also measured using GC/IRMS. RESULTS: The range of δ(18)O values of rainwater (-11.15 to -4.91) was wider than that of soil water (-7.94 to -5.64). The δ(18)O value of soil water at 50 cm depth was not immediately affected by rainwater. At 10 cm and 20 cm depths of soil between tea plant rows, linear regression analyses of δ(18)O-N(2)O (relative to δ(18)O-NO(3)(-)) versus δ(18) O-H(2)O (relative to δ(18)O-NO(3)(-)) yielded slopes of 0.76-0.80 and intercepts of 31-35. CONCLUSIONS: In soil between tea plant rows, the fraction of O-exchange between H(2)O and N(2)O precursors was approximately 80%. Assuming that denitrification dominated N(2)O production, the net (18)O-isotope effect for denitrification (NO(3)(-) reduction to N(2)O) was approximately 31-35, reflecting the upland condition of the tea field.
Assuntos
Camellia sinensis/química , Nitratos/química , Isótopos de Oxigênio/análise , Chuva/química , Solo/química , Água/química , Agricultura , Camellia sinensis/metabolismo , Desnitrificação , Japão , Espectrometria de Massas , NitrificaçãoRESUMO
Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been reported to have potent anti-inflammatory properties. However, the effect of ginsenoside Rg1 on lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice was unknown. The present study was designed to investigate the protective role of Rg1 on LPS-induced ALI and explore the potential mechanisms. The mice were divided randomly into four groups: the sham group, the LPS group and the LPS+Rg1 (40 mg/kg or 200mg/kg) pretreatment groups. All mice received Rg1 or an equivalent volume of phosphate buffer saline (PBS) intraperitoneally 1h before LPS administration. Edema quantification, histology, and apoptosis were detected 6h after LPS administration. The number of inflammatory cells, the percentage of alternative activated (M2) macrophages and the exudate quantification in bronchoalveolar lavage fluid (BALF) were evaluated. The caspase 3 expression, and the levels of phosphorylated IκB-α and p65 were tested. The results showed that the Rg1 pretreatment group markedly improved lung damage, modulated the infiltration of neutrophils and M2 macrophages, prevented the production of protein and proinflammatory cytokines in BALF, and inhibited apoptosis in lung. We also found that Rg1 suppressed NF-κB and caspase 3 activation. These data suggest that Rg1 plays a protective role against LPS-induced ALI by ameliorating inflammatory responses, regulating the infiltration of M2 macrophages, and inhibiting pulmonary cell apoptosis.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Ginsenosídeos/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Citocinas/imunologia , Ginsenosídeos/farmacologia , Lipopolissacarídeos , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/imunologiaRESUMO
BACKGROUND: Salidroside (SDS) is the main effective component of Rhodiola rosea L with a variety of pharmacologic properties. The objective of this study was to investigate the efficacy of SDS in the treatment of experimental sepsis in mice and explore the possible underlying action mechanisms. METHODS: Sepsis was induced in C57BL/6 male mice via cecal ligation and puncture (CLP). The animals were divided into three groups as follows: sham, CLP, and CLP plus SDS. SDS (50 mg/kg) was injected intraperitoneally 1 h after operation. Postoperative survival of the mice, bacterial clearance in blood and peritoneal lavage fluid, cytokine secretion in blood, and histology of lung were evaluated. In addition, apoptosis of immune cells in the spleen and thymus were examined, respectively. RESULTS: SDS administration prolonged the survival of the septic mice, inhibited the proinflammatory responses, and enhanced bacterial clearance. It also alleviated the pathologic changes in the lung and inhibited the apoptosis of immune cells in the spleen and thymus after CLP challenge. CONCLUSIONS: SDS exerts a protective effect in CLP-induced sepsis by attenuating the proinflammatory responses, enhancing bacterial clearance, and preserving adaptive immunity. SDS may be a promising therapeutic strategy for the treatment of sepsis.
Assuntos
Glucosídeos/uso terapêutico , Fenóis/uso terapêutico , Fitoterapia , Rhodiola , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Sepse/sangue , Sepse/complicações , Baço/efeitos dos fármacos , Timo/efeitos dos fármacosRESUMO
Salidroside, isolated from the medicinal plant Rhodiola, was reported to serve as an "adaptogen." This study was designed to explore the protective effect of salidroside on concanavalin A- (Con A-) induced hepatitis in mice and investigate potential mechanisms. C57BL/6 mice were randomly divided into control group, Con A group, and salidroside group. Salidroside (50 mg/kg) was injected intravenously followed by Con A administration. The levels of ALT, AST, inflammatory cytokines and CXCL-10 were examined. The pathological damage of livers was assessed, the amounts of phosphorylated IκBα and p65 were measured, and the numbers of CD4(+) and CD8(+) T lymphocytes in the blood, spleen and infiltrated in the liver were calculated. Our results showed that salidroside pretreatment reduced the levels of ALT, AST dramatically and suppressed the secretion of proinflammatory cytokines through downregulating the activity of NF-κB partly. Salidroside altered the distribution of CD4(+) and CD8(+) T lymphocyte in the liver and spleen through regulating CXCL-10 and decreased the severity of liver injuries. In conclusion, these results confirm the efficacy of salidroside in the prevention of immune mediated hepatitis in mice.
Assuntos
Concanavalina A/farmacologia , Citocinas/metabolismo , Glucosídeos/uso terapêutico , Hepatite/tratamento farmacológico , Hepatite/imunologia , Linfócitos/citologia , Fenóis/uso terapêutico , Animais , Movimento Celular/fisiologia , Citometria de Fluxo , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Ginsenoside Rg1, the major effective component of ginseng, possesses a variety of pharmacologic activities. The objective of this study was to investigate the effects of Rg1 on liver ischemia-reperfusion (IR) injury and explore its potential mechanisms. MATERIALS AND METHODS: Liver warm IR injury was achieved by occluding the portal vein and hepatic artery for 1 h followed by 6-h reperfusion. Eighteen mice were equally randomized into three groups: sham group, IR group, and IR plus Rg1 group (n = 6 mice per group). Mice received an intravenous dose of 20 mg/kg Rg1 or an equivalent volume of saline before ischemic insult. Liver samples and serum were collected for analyses. Serum aminotransferase, histopathology, and apoptosis were determined. Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylation of nuclear factor kappa B (NF-κB) p65 was assessed by Western blotting. In addition, the effect of Rg1 in a simulated IR model in vitro was also investigated. Rg1 (100 ug/mL and 500 ug/mL) was administered 1 h before hypoxia insult, and then apoptosis was measured after 12-h reperfusion. RESULTS: Liver IR injury led to a dramatic increase in aminopherase activity, apoptosis and necrosis of hepatocytes, and production of proinflammatory cytokines. Pretreatment with Rg1 protected mice from IR-induced liver injury. Treatment with a high-dose Rg1 (500 ug/mL) significantly suppressed apoptosis compared with a lower dose or control (both P < 0.001). Phosphorylation of NF-κB p65 was increased significantly in IR group, and administration with Rg1 suppressed the level of phosphorylation. CONCLUSIONS: Pretreatment of mice with Rg1 reduced hepatocellular apoptosis and inhibited inflammatory response, which was in part through the NF-κB signaling pathway. Rg1 may provide a novel therapeutic strategy for the treatment of IR-induced liver injury.
Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Hepatite/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Hepatite/imunologia , Hepatite/patologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Necrose/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Imunologia de Transplantes/efeitos dos fármacos , Isquemia QuenteRESUMO
OBJECTIVE: To investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats. METHODS: Forty SPF SD rats were divided into sham group (n=10),model group (n=10), Jianpi Qinghua group (n=10) and losartan group (n=10). Rat chronic renal failure was induced by 5/6 nephrectomy (Platt method) in model, Jianpi Qinghua and losartan groups, and rats in sham group received sham operation. Jianpi Qinghua decoction (3.9 g 200 g(-1)) or losartan (3.3 g 200 g(-1)) daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days, respectively, Rats in sham and model groups were orally administered with saline of the same volume. The serum levels of creatinine and urea nitrogen were measured by biochemical method, the expression of MAPK p38 was detected by Western Blot,and renal pathological changes were observed with hematoxylin-eosin staining. RESULTS: Compared to model group,serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly (42.67 ± 5.98 or 40.90 ± 5.07 compared with 60.90 ± 9.54, both P<0.01), the expression of MAPK p38 was significantly down-regulated (0.555 ± 0.004 or 0.587 ± 0.045 compared with 0.930 ± 0.265,both P<0.01) and serum urea nitrogen was also decreased (8.56 ± 0.75 or 7.97 ± 0.86 compared with 8.62 ± 0.62,both P<0.05). The renal pathology in the model group presented glomerular mesangial proliferation,hyperplasia of glomenrulus mesangial cells and interstitial inflammation. Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups. CONCLUSION: Jianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure, which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/enzimologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the effect of Jianpi Qinghua Recipe ( JPQHR) on angiotensin II/NADPH oxidase pathway in 5/6 nephrectomized rat renal failure model and the underlying mechanisms. METHODS: The animals were divided into 4 groups: the sham-operated group, the renal failure group, the JPQHR-treated group and the losartan-treated group. After 60-days therapy, serum nitrogen and creatinine were measured. The expression of angiotensin II type 1 receptor (AT1) protein and the expression of p47phox mRNA in renal tissue was determined. SOD and MDA were also examined. RESULTS: Compared with the sham-operated group, the levels of SCr and serum BUN and the AT1 protein and p47phox mRNA expression in the renal failure group were significantly increased. The activities of SOD in renal tissue from the renal failure group was significantly down-regulated while MDA was up-regulated (P<0.05). Compared with the renal failure group, the levels of SCr and serum BUN and the AT1 protein and p47phox mRNA expression in both JPQHR-treated group and losartan-treated group were significantly decreased. The activities of SOD in renal tissue from JPQHR-treated group and losartan-treated group were significantly up-regulated whereas the content of MDA were down-regulated (P<0.05). Compared with the losartan-treated group, the activities of SOD in renal tissue from the JPQHR-treated group was obviously increased (P<0.05), the decrease in AT1 protein and p47phox mRNA was more evident but not statistically different (P>0.05). The level of SCr and serum BUN and the content of MDA were also not statistically different (P>0.05). CONCLUSION: Through decrease the expression of angiotensin II and NADPH oxidase, JPQHR can reduce the oxidative stress in chronic renal failure and delay the renal fibrosis progression.
Assuntos
Angiotensina II/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , NADPH Oxidases/metabolismo , Nefroesclerose/prevenção & controle , Animais , Falência Renal Crônica/fisiopatologia , Masculino , Nefrectomia , Nefroesclerose/etiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
The effect of ginsenoside Rg1 (Rg1) on hepatic damage caused by concanavalin A (Con A) has not been fully elucidated. This study was designed to evaluate the protective effect of Rg1 on Con A-induced hepatitis in mice and explore the potential mechanisms of this effect. C57BL/6 mice were divided randomly into the following four experimental groups: phosphate-buffered saline group, Rg1 group, Con A group, Con A + Rg1 group. Mice received Rg1 (20 mg/kg) 3 h before intravenous administration of Con A (15 mg/kg). Levels of alanine transaminase, aspartate transaminase and cytokine production were measured, the amount of phosphorylated IκBα and p65 were tested, the numbers of CD4(+) and CD8(+) T lymphocytes infiltrated in the blood, spleen and liver were calculated, intercellular adhesion molecule-1 (ICAM-1) and interferon-inducible chemokine-10 (CXCL-10) levels were measured and histological examination of the livers was conducted. Pretreatment with Rg1 markedly reduced the elevated levels of serum aminotransferase, ameliorated liver damage and suppressed proinflammatory cytokines secretion via inhibition NF-κB activity following Con A injection of mice. Furthermore, Rg1 administration reduced ICAM-1 and CXCL-10 mRNA expression in the liver as well as the number of CD4(+) and CD8(+) T lymphocytes infiltrating in the liver. Rg1 reduced the incidence of liver damage through inhibition of the proinflammatory response and suppressed the recruitment of CD4(+) and CD8(+) T lymphocytes to the liver. These data indicate that Rg1 represents a novel agent for the treatment of T lymphocyte-dependent liver injury.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citocinas/metabolismo , Ginsenosídeos/farmacologia , Animais , Western Blotting , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Fármacos do Sistema Nervoso Central/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Concanavalina A/toxicidade , Citocinas/genética , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição RelA/metabolismoRESUMO
OBJECTIVE: To observe the balance of T help cell1/2 (Th1/Th2), the changes of correlated proinflammatory cytokines (IFN-gamma and IL-4), and regulated on activation normal T cell expressed and secreted (RANTES), and the abnormal expression of IL-17, the effector of T help cell17 (Th17) in chronic glomerulonephritis (CGN)patients with Shaoyang disease, thus revealing the mechanisms of Xiaochaihu Decoction (XD) for treating proteinuria of CGN patients according to the theory of mediating Shaoyang meridian. METHODS: Totally 70 CGN patients with Shaoyang disease were randomly assigned to two groups, the treatment group (treated by XD) and the control group [treated by Shenyan Kangfu Tablet (SKT)], 35 in each group. Besides, 20 healthy volunteers were recruited as the healthy control group. Besides, routine therapy of chronic kidney disease (CKD), patients in the treatment group and the control group were treated with XD and SKT respectively for 4 weeks. The changes of Chinese medical syndrome, the effectiveness, 24-h urinary protein, renal functions, the peripheral blood IFN-gamma, IL-4, Th1/Th2, IL-17, and RANTES were compared. RESULTS: Before treatment the Th1/Th2, IL-17, and RANTES of the two treated groups were higher, and the IL-4 level was lower than those of the healthy control group (P < 0.05). After treatment the improvement of Chinese medical syndrome, main symptoms, the effectiveness was better in the XD group than in the SKT group (P < 0.05, P < 0.01). The proteinuria obviously decreased in the treatment group, with the efficacy superior to the SKT group (P < 0.05). The Th1/Th2, IL-17, and RANTES decreased to various degrees when compared with the SKT group (P < 0.05, P < 0.01). The IL-4 level increased more obviously in the treatment group than in the control group (P < 0.05). There was no statistical difference in the improvement of the renal function (P > 0.05). CONCLUSIONS: The immune disorder of the CGN patients with Shaoyang disease was correlated with Th1/Th2 imbalance, and abnormal changes of Th17 cell functions and RANTES. XD could improve the inflammation by regulating the immune disorder of CGN patients with Shaoyang disease, which proved that the theory of mediating Shaoyang meridian could be used to improve the inflammation of CGN patients, thus relieving the proteinuria.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Proteinúria/tratamento farmacológico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Quimiocina CCL5/metabolismo , Doença Crônica , Feminino , Glomerulonefrite/imunologia , Glomerulonefrite/metabolismo , Humanos , Interferon gama/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Proteinúria/imunologia , Proteinúria/metabolismo , Equilíbrio Th1-Th2 , Células Th17/imunologia , Adulto JovemRESUMO
BACKGROUND: Unbalanced inflammatory response and lymphocyte apoptosis are the main reasons for high mortality in patients with sepsis. Ginsenoside Rg1 (Rg1), the most important component isolated from Panax ginseng, has long been used to treat inflammatory and immune-related diseases. We designed this study to investigate the therapeutic effect of this agent on cecal ligation and puncture (CLP)-induced sepsis in mice. MATERIALS AND METHODS: We randomly divided C57BL/6 mice into four experimental groups: sham, sham plus Rg1, CLP, and CLP plus Rg1. We intravenously injected Rg1 (20 mg/kg) 1 h after CLP and evaluated survival, bacterial clearance, cytokine production, histology, neutrophil emigration, and lymphocyte apoptosis. RESULTS: Our study showed that treatment with Rg1 significantly improved survival in septic mice (P < 0.01). Rg1 administration suppressed the inflammatory response and enhanced bacterial clearance. Histologic examination of lung and liver showed only minor abnormalities in mice that received Rg1. In addition, Rg1 increased neutrophil counts in peritoneal cavity and inhibited lymphocyte apoptosis in thymus and spleen. CONCLUSIONS: Ginsenoside Rg1 has a protective role against CLP-induced polymicrobial sepsis by attenuating the proinflammatory response, enhancing innate immunity and preserving adaptive immunity. Rg1 could be a promising new agent for treatment of sepsis.
Assuntos
Apoptose/efeitos dos fármacos , Coinfecção/mortalidade , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Inflamação/prevenção & controle , Linfócitos/patologia , Sepse/mortalidade , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ceco/lesões , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Modelos Animais de Doenças , Inflamação/patologia , Ligadura/efeitos adversos , Linfócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Punções/efeitos adversos , Sepse/tratamento farmacológico , Sepse/microbiologia , Baço/efeitos dos fármacos , Baço/patologia , Taxa de SobrevidaRESUMO
Total saponins of panax ginseng (TSPG) are the major active components in panax ginseng. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TSPG on the maturation and immune function of DCs. Compared with those untreated, the DCs pre-treated with TSPG and then induced by oxidized-LDL exhibited a significantly lower expression of the maturation-associated markers of CD40, CD86, HLA-DR, and CD1a, together with an increased endocytosic function as well as decreased secretions of cytokine. However, silencing the expression of PPARgamma in DCs, the inhibitory effect of TSPG on the maturation DCs was significantly reduced. In conclusion, TSPG could inhibit the maturation of DCs induced by oxidized-LDL which suggests beneficial effects on atherosclerosis and this effect was partly dependent on the PPARgamma pathway at least.