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1.
Zhonghua Nan Ke Xue ; 25(8): 734-738, 2019 Aug.
Artigo em Zh | MEDLINE | ID: mdl-32227718

RESUMO

The androgen receptor signaling pathway is a key factor in the development and progression of prostate cancer. Aldo-keto reductases AKR1C1-AKR1C4 play an important role in the synthesis and metabolism of androgens in the body, and their expressions influence the androgen receptor signaling pathway and consequently the development and progression of prostate cancer. For the treatment of androgen-resistant prostate cancer, which cannot be cured currently, Chinese medicine and phytotherapy are receiving more and more attention for the mild, long-lasting and multi-target advantages of the small molecules of traditional Chinese medicine. This review summarizes the roles of aldo-keto reductases in the progression of prostate cancer and compares the anti-tumor activities of small molecules in Chinese medicine targeting aldo-keto reductases, hoping to provide a basis for the discovery of new targets for prostate cancer and the development of anti-tumor drugs.


Assuntos
Aldo-Ceto Redutases , Medicina Tradicional Chinesa , Neoplasias de Próstata Resistentes à Castração/enzimologia , Aldo-Ceto Redutases/antagonistas & inibidores , Androgênios , Humanos , Masculino
2.
BMC Complement Altern Med ; 15: 342, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26427787

RESUMO

BACKGROUND: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. METHODS: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α. RESULTS: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups. CONCLUSIONS: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Actinas , Inibidores da Angiogênese/uso terapêutico , Animais , Tetracloreto de Carbono , Colágeno/efeitos adversos , Hidroxiprolina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática Experimental/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
3.
BMC Complement Altern Med ; 12: 33, 2012 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-22471627

RESUMO

BACKGROUND: Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFß1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFß1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD. METHODS: A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFß1 signaling pathway was evaluated by western blotting and laser confocal microscopy. RESULTS: Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFß1, and activated TGFß1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFß1, TGFß1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression. CONCLUSION: IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFß1-Smad3 and TGFß1-ERK1/2 signaling pathways.


Assuntos
Doenças Biliares/tratamento farmacológico , Ducto Colédoco/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Astrágalo , Astragalus propinquus , Doenças Biliares/metabolismo , Doenças Biliares/patologia , Ducto Colédoco/metabolismo , Ducto Colédoco/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose/tratamento farmacológico , Ligadura , Fígado/citologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Fitoterapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo
4.
Front Pharmacol ; 11: 423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32317976

RESUMO

Constipation is a common gastrointestinal disorder without effective treatment approach. Buzhongyiqi decoction (BZYQD) is a classical formula that has been commonly used for gastrointestinal disorders for nearly 1,000 years. In this study, we aimed to investigate the protective effect of BZYQD against loperamide-induced constipation and its potential mechanism. Rats with loperamide-induced constipation were orally administered BZYQD. BZYQD treatment obviously increased the small intestinal transit rate and alleviated colon tissue pathological damage. Subsequently, serum metabolomics study was performed to identify the metabolites affected by BZYQD. Metabolomics identified that the levels of 17 serum metabolites, including prostaglandin E2 (PGE2), arachidonic acid (AA), and inositol, were significantly changed in BZYQD-treated group compared with those in the loperamide-induced group. Pathway analysis revealed that those metabolites were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, ascorbate and aldarate metabolism, inositol phosphate metabolism. Additionally, BZYQD treatment down-regulated the cyclooxygenase-2 expression and decrease production of the proinflammatory mediator PGE2. Further study revealed that BZYQD administration decreased serum levels of the inflammatory factors IL-1ß and TNF-α, inhibited phosphorylation of the nuclear transcription factor NF-κB, and down-regulated expression of the inflammatory factors IL-1ß and IL-6 in the constipated rat colon. Moreover, BZYQD treatment also increased serum levels of inositol, motilin and gastrin, and promoted gastrointestinal motility. In conclusion, the present study suggested that BZYQD exerted a protective effect against loperamide-induced constipation, which may be associated with its role in regulation of multiple metabolic pathways.

5.
Zhong Xi Yi Jie He Xue Bao ; 5(2): 130-3, 2007 Mar.
Artigo em Zh | MEDLINE | ID: mdl-17352865

RESUMO

OBJECTIVE: To investigate the pathological factors of syndrome pathomechanism through studying the correlation between syndromes of posthepatitic cirrhosis and biological parameters. METHODS: Clinical information of three hundred and fifty-five patients with posthepatitic cirrhosis was collected and the database was established. Parameters with statistical significance were analyzed with multi-factor regression analysis to investigate the main influencing factors of the syndromes of posthepatitic cirrhosis. RESULTS: Formulae of six syndromes, including syndrome of yin deficiency of liver and kidney, syndrome of damp heat, syndrome of stagnated heat smoldering, syndrome of yang deficiency of spleen and kidney, syndrome of stagnation of liver qi and spleen deficiency and syndrome of blood stasis due to qi deficiency, were established with stepwise regression analysis. CONCLUSIONS: One of the pathophysiological bases of syndrome of blood stasis due to qi deficiency in cirrhosis is synthetic dysfunction of hepatocytes. The pathophysiological basis of syndrome of damp heat is inflammatory injury, which is also syndrome of stagnated heat smoldering in cirrhosis patients. The relationship between syndrome of yin deficiency of liver and kidney and stasis and damp heat may be the pathophysiological basis of the posthepatitic cirrhosis..


Assuntos
Cirrose Hepática/diagnóstico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Qi , Análise de Regressão , Síndrome , Deficiência da Energia Yang/sangue , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yin/sangue , Deficiência da Energia Yin/diagnóstico
6.
Am J Chin Med ; 45(1): 85-104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28081630

RESUMO

Notch signaling has been demonstrated to be involved in ductular reactions and fibrosis. Previous studies have shown that Huang Qi Decoction (HQD) can prevent the progression of cholestatic liver fibrosis (CLF). However, whether HQD affects the Notch signaling pathway is unclear. In this study, CLF was established by common bile duct ligation (BDL) in rats. At the end of the first week, the rats were randomly divided into a model group (i.e., BDL), an HQD group, and a sorafenib positive control group (SORA) and were treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, and -4, Jagged (JAG) 1, and Delta like (DLL)-1, -3, and -4. The results showed that HQD significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs compared with the BDL group. In addition, HQD significantly decreased the protein and mRNA expressions of TGF-[Formula: see text]1 and [Formula: see text]-SMA. In contrast, HQD significantly enhanced expression of the Smad 7 protein. HQD also reduced biliary epithelial cell proliferation, and reduced the mRNA levels of CK7, CK8, CK18, SRY-related high mobility group-box gene (SOX) 9, epithelial cell adhesion molecule (EpCAM) and the positive areas of CK19 and OV6. In addition, the mRNA and protein expressions of Notch-3, -4, JAG1, and DLL-1, -3 were significantly reduced in the HQD compared to the BDL group. These results demonstrated that HQD may prevent biliary liver fibrosis through inhibition of the Notch signaling pathway, and it may be a potential treatment for cholestatic liver disease.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Receptores Notch/efeitos dos fármacos , Actinas/efeitos dos fármacos , Actinas/genética , Actinas/metabolismo , Animais , Astragalus propinquus , Sistema Biliar/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colestase/etiologia , Colestase/prevenção & controle , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Molécula de Adesão da Célula Epitelial/efeitos dos fármacos , Molécula de Adesão da Célula Epitelial/genética , Células Epiteliais/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1/efeitos dos fármacos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Queratinas/efeitos dos fármacos , Queratinas/genética , Ligadura , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ratos , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad7/efeitos dos fármacos , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
7.
Zhonghua Gan Zang Bing Za Zhi ; 13(8): 563-6, 2005 Aug.
Artigo em Zh | MEDLINE | ID: mdl-16092975

RESUMO

OBJECTIVE: To study the proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis. METHODS: Wistar rats were injected subcutaneously with 40% CCl4-olive oil twice weekly for 12 weeks. Liver tissues were obtained at the end of 4, 8, 12 and 16 weeks for histological examination, hydroxyproline (Hyp) assay and proteomic analysis. After two dimension electrophoresis (2-DE), the silver stained gels were analyzed with PDQUEST 2-DE. More than 30 differentially expressed proteins were identified by MALDI-TOF-MS. RESULTS: The degree of collagen deposition and hydroxyproline content of the fibrotic livers increased continuously during the 12 weeks of CCl4 administration, peaked at the end of week 12 (P < 0.05) and declined significantly at week 16 (P < 0.05). Significant differences were observed in two parameters at each time point between the control and the model group. Meanwhile, dramatic change of hepatic proteome in the model group rats was also seen. Differentially expressed proteins identified by MALDI-TOF-MS were categorized as proliferation-related proteins/enzymes (proliferating cell nuclear antigen p120, p40 and cyclin F ubiquitin-conjugating enzyme 7 UBC7), and apoptosis-related proteins, mainly caspase-12 which was absent in the control rats. CONCLUSION: Proliferation and apoptosis related proteins are expressed dynamically in different stages of rat liver fibrosis induced by CCl4.


Assuntos
Cirrose Hepática Experimental/metabolismo , Proteínas/metabolismo , Proteoma/metabolismo , Animais , Apoptose , Tetracloreto de Carbono , Intoxicação por Tetracloreto de Carbono , Caspase 12/metabolismo , Proliferação de Células , Hidroxiprolina/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Masculino , Ratos , Ratos Wistar
8.
J Ethnopharmacol ; 148(1): 182-9, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23619018

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC). However, no potential action mechanisms and active compounds had been systematically investigated. AIM OF THE STUDY: To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats. MATERIALS AND METHODS: XXD was administered orally for 8 days at a dosage of 2 or 4g/kg/day. Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected. Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa Bp65 (NF-κBp65) in colon tissues were examined. Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD. RESULTS: XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-α and NF-κBp65, and increasing the production of IL-10 in colon tissues. Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively. CONCLUSIONS: The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Interleucina-10/metabolismo , Masculino , Peroxidase/metabolismo , Fitoterapia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA , Resultado do Tratamento , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/metabolismo
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