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1.
J Ethnopharmacol ; 264: 113052, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32535239

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. as a traditional Asian medicinal plant, roots and rhizomes (Danshen) are used to treat chronic hepatitis and coronary heart disease. In recent years, the medicinal value of S. miltiorrhiza stems and leaves total phenolic acids extract (JF) similar to roots and rhizomes has received increasing attention. S. miltiorrhiza roots and rhizome tanshinone extract (DT) has a good anti-inflammatory effect. AIM OF THE STUDY: To explore the therapeutic effect and possible molecular mechanisms of JF and DT alone or in combination on dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Colitis was induced by received 2% DSS in drinking water for 7 consecutive days. Then mice were administered orally for 7 days. Disease activity index (DAI) scores and body weight were recorded daily. After the end of the experiment, colon was removed, colon length was measured and histopathological analysis was performed. Inflammatory factors expression was determined by ELISA, its mRNA expression was detected by real-time quantitative PCR, and the expression of related proteins on TLR4/PI3K/AKT/mTOR signal was analyzed by Western blot. RESULTS: Treatment with JF and DT alone or in combination reduced DAI scores, increase body weight, improved colon shortening, and decreased colon histology scores. In addition, the expression level of inflammatory factors was inhibited. The combination of JF and DT had a better inhibitory effect on inflammatory factors compared to JF alone. We also found that DT alone and JF combined with DT inhibited TLR4/PI3K/AKT/mTOR signaling-related proteins expression levels (including TLR4, p-PI3K p110α/PI3K p110α, p-AKT (ser473)/AKT, mTOR, p-mTOR, NF-κB p65), showing an effective anti-inflammatory effect. CONCLUSIONS: We demonstrated for the first time that, JF and DT alone or in combination effectively ameliorated DSS-induced ulcerative colitis in mice, possibly by inhibiting the TLR4/PI3K/AKT/mTOR signaling pathway.

2.
Indian J Pharmacol ; 52(2): 108-116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565598

RESUMO

We investigate the protective effect of Carthamus tinctorius L. (CTL, also known as Honghua in China or Safflower) on cerebral ischemia-reperfusion and explored the possible mechanisms on regulating apoptosis and matrix metalloproteinases (MMPs). High-performance liquid chromatography method with diode array detection analysis was established to analyze the components of CTL. Middle cerebral artery occlusion rats model was established to evaluate Neurological Function Score and hematoxylin-eosin staining, as well as triphenyltetrazolium was used to examine the infarction area ratio. Transferase-mediated dUTP nick-end labeling was performed for the apoptosis. Apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), Bax and Caspase3, and MMPs-related MMP2, MMP9, tissue inhibitor of metalloproteinases 1 (TIMP1) in ischemic brain, were assayed by Western blot, reverse transcription polymerase chain reaction, and immunohistochemistry. The data showed that CTL (2, 4 g crude drug/kg/d) treatment could significantly reduce the ischemic damage in brain tissue and improve a significant neurological function score. In addition, CTL could also attenuate apoptosis degree of brain tissues and regulate Bcl-2, Bax, and Caspase 3 and also have a significant decrease on MMP-9 expression, followed by a significant increase of TIMP1 protein expression. These findings indicated that regulation of CTL on apoptosis and MMPs contributed to its protective effect on ischemia/reperfusion injury.

3.
Zhongguo Zhong Yao Za Zhi ; 43(7): 1484-1491, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29728041

RESUMO

To evaluate the effect and mechanism of aerial parts of Salvia miltiorrhiza(SM) on high sugar-induced Drosophila melanogaster metabolic disorder model. The levels of glucose, triglyceride and protein in SM were detected; nymphosis time was recorded, and the reliability of metabolic disorder model as well as the mechanism of aerial parts of SM were evaluated based on metabonomics. The results showed that the levels of glucose and triglyceride in model group were significantly higher than those in normal control group(P<0.05). As compared with the model group, the glucose level was significantly decreased in gliclazide(GLZ) group, SM medium(SM-M) and high(SM-H) dose groups(P<0.05, P<0.01); the triglyceride level was significantly decreased in GLZ group and SM-H group(P<0.05, P<0.01). By principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), the metabolic level of model ones was recovered to a certain degree after intervention by aerial parts of SM. Seventeen marker compounds and four major metabolic pathways were obtained by screening differential metabolites, comparing literature and retrieving the database. The aerial parts of SM may regulate glycolipid metabolism through the impact on histidine metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, cysteine and methionine metabolism and glycerolipid metabolism. Extract from aerial parts of SM can regulate the glycolipid metabolism of D. melanogaster metabolic disorder model and make it return to normal condition. This paper provides reference for the value discovery and resource utilization of the aerial parts of S. miltiorrhiza.


Assuntos
Drosophila melanogaster , Glicolipídeos/metabolismo , Doenças Metabólicas/tratamento farmacológico , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Animais , Componentes Aéreos da Planta/química , Reprodutibilidade dos Testes , Açúcares
4.
J Exp Clin Cancer Res ; 36(1): 178, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29216925

RESUMO

BACKGROUND: Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies. METHODS: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization. PC cell line (PC3 cell) was transfected with miR-193a-5p mimic or its inhibitor, and then cell apoptosis and the expression of its downstream genes Bach2 and HO-1 were detected by TUNEL staining and Western blotting. Luciferase reporter assay was used to detect the effect of miR-193a-5p and Bach2 on HO-1 expression. Xenograft animal model was used to test the effect of miR-193a-5p and docetaxel on PC3 xenograft growth. RESULTS: miR-193a-5p was upregulated in PC tissues and PC cell lines, with significant suppression of PC3 cell apoptosis induced by oxidative stress. Mechanistically, miR-193a-5p suppressed the expression of Bach2, a repressor of the HO-1 gene, by directly targeting the Bach2 mRNA 3'-UTR. Docetaxel treatment modestly decreased Bach2 expression and increased HO-1 level in PC3 cells, whereas a modest increase of HO-1 facilitated docetaxel-induced apoptosis. Notably, docetaxel-induced miR-193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis, as evidenced by the increased Bcl-2 and decreased Bax expression. Accordingly, silencing of miR-193a-5p enhanced sensitization of PC3 cells to docetaxel-induced apoptosis. Finally, depletion of miR-193a-5p significantly reduced PC xenograft growth in vivo. CONCLUSIONS: Silencing of miR-193a-5p or blockade of the miR-193a-5p-Bach2-HO-1 pathway may be a novel therapeutic approach for castration-resistant PC.


Assuntos
Antineoplásicos/farmacologia , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/farmacologia , Idoso , Animais , Modelos Animais de Doenças , Docetaxel , Inativação Gênica , Humanos , Masculino , Camundongos , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Transfecção , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Artigo em Inglês | MEDLINE | ID: mdl-28348625

RESUMO

Goutengsan, a Chinese herbal formula, potential protection on Alzheimer's disease (AD) has been less reported. In current study, we investigated the protection of Goutengsan on Aß1-42-induced pheochromocytoma-derived cells (PC12). Furthermore, the components from Goutengsan in rat plasma were identified by microdialysis (MD) for in vivo sampling. Meanwhile, the protection of components identified was also verified. At last, we found that Goutengsan has a potential protective effect on Aß1-42-induced PC12 cells via reducing cells damage and increasing cells vitality as well as six components (pachymic acid, liquiritin, rhynchophylline, isorhynchophylline, corynoxeine, and isocorynoxeine) which may be effective components. This study helps to understand the treatment of Goutengsan for AD and would facilitate the clinical and further studies for this formula.

6.
J Ethnopharmacol ; 193: 433-444, 2016 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-27664441

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN. However, the underlying mechanisms of MC-TG for treating DN are still unknown. AIM OF THE STUDY: To explore the role of ER stress-related inflammatory responses in the progression of DN, and to investigate the underlying protective mechanisms of MC-TG in kidney damage. MATERIALS AND METHODS: DN rats and advanced glycation end-products (AGEs) induced HBZY-1 cell dysfunction were established to evaluate the protective effect of MC-TG on ameliorating renal injury. Evaluation of pathological lesions was performed by Masson staining and transmission electron microscopy (TEM). Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), glucose regulated protein 78 (GRP78/Bip), as well as spliced X box binding protein 1(XBP-1(s)) levels in rat serum were detected by an enzyme-linked immunosorbent assay (ELISA). Furthermore, western blotting (WB) was applied to detect the protein expressions including IL-6, MCP-1, intercellular cell adhesion molecule-1 (ICAM-1), GRP78/Bip, XBP-1 (s), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), and phosphorylated nuclear factor κB p65 (p-NF-κB p65) in vivo and in vitro. Immunohistochemistry (IHC) was carried out to determine the phosphorylation of IRE1α and NF-κB p65 in kidney tissues. RESULTS: Pretreatment with MC-TG could markedly improve renal insufficiency and pathologic changes. It could down-regulate ER stress-related factors GRP78/Bip, XBP-1(s) levels, and also reduce the pro-inflammatory molecules IL-6, MCP-1, and ICAM-1 expressions. Furthermore, a significant decrease in phosphorylation of IRE1α and NF-κB p65 by the treatment of MC-TG. CONCLUSIONS: These findings indicated that MC-TG ameliorated ER stress-related inflammation in the pathogenesis of DN, wherein the protective mechanism might be associated with the inhibition of IRE1/NF-κB activation. Thus, MC-TG might be a potential therapeutic candidate for the prevention and treatment of DN.


Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glicosídeos/farmacologia , Células Mesangiais/efeitos dos fármacos , Insuficiência Renal/prevenção & controle , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Glicosídeos/química , Glicosídeos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Células Mesangiais/metabolismo , Células Mesangiais/ultraestrutura , Paeonia/química , Fosforilação , Fitoterapia , Plantas Medicinais , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Insuficiência Renal/etiologia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Terpenos/química , Terpenos/isolamento & purificação , Fator de Transcrição RelA/metabolismo
7.
J Ethnopharmacol ; 185: 162-70, 2016 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-26988565

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold "Clearing heat and detoxification, Removing liver fire for improving eyesight" functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored. MATERIALS AND METHODS: The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats' model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30mg/kg). The cell supernatant and rats' serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs. RESULTS: After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0µM, 25.0µM and 125.0µM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA. CONCLUSION: The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.


Assuntos
Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Glucose/toxicidade , Vasos Retinianos/citologia , Ácido Tauroquenodesoxicólico/farmacologia , Animais , Regulação Enzimológica da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular , Masculino , Camundongos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo
9.
Planta Med ; 82(4): 322-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26824623

RESUMO

A flavonoid fraction of Herba Epimedii, including eight flavonoid glycoside compounds, epimedoside A, ikarisoside F, baohuoside II, sagittatoside A, sagittatoside B, 7-O-rhamnosyl icariside II, 2"-O-rhamnosyl icariside II, and baohuoside I, was isolated and prepared from the leaves of Herba Epimedii. This study was conducted to assess the potential effect of the flavonoid fraction of Herba Epimedii on osteoporosis in ovariectomized rats. Rats received repeated administration of a vehicle (ovariectomized), the flavonoid fraction of Herba Epimedii (7.5, 15, 30 mg/kg/d), and ipriflavone (200 mg/kg/d) once a day for 8 weeks, beginning 4 weeks after ovariectomization. Then, the bone turnover markers, bone biomechanical properties, trabecular architecture, and related protein expressions were evaluated by biochemical assay kits, mechanical testing, microcomputed tomography, immunohistochemical evaluation, and Western blot analysis. Treatment with the flavonoid fraction of Herba Epimedii (15, 30 mg/kg/d) and ipriflavone (200 mg/kg/d) significantly increased bone strength while dramatically inhibiting the serum alkaline phosphatase and tartrate-resistant acid phosphatase levels in ovariectomized rats. Furthermore, the flavonoid fraction of Herba Epimedii also increased osteoprotegerin protein expression and reduced the receptor activator of nuclear factor-κB ligand protein expression compared with ovariectomized rats. In addition, the microcomputed tomography results showed that the flavonoid fraction of Herba Epimedii treatment significantly improved trabecular bone mineral density and restored the bone microarchitecture in ovariectomized rats. Therefore, our results indicated that the flavonoid fraction of Herba Epimedii might be beneficial for improving postmenopausal osteoporosis and should be considered as a promising candidate for treating postmenopausal osteoporosis.


Assuntos
Osso e Ossos/metabolismo , Epimedium/química , Flavonoides/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Feminino , Ovariectomia , Ratos , Ratos Sprague-Dawley
10.
Mol Med Rep ; 13(2): 1475-86, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26718010

RESUMO

Methylglyoxal (MGO)-induced carbonyl stress and pro-inflammatory responses have been suggested to contribute to endothelial dysfunction. Curcumin (Cur), a polyphenolic compound from Curcuma longa L., may protect endothelial cells against carbonyl stress-induced damage by trapping dicarbonyl compounds such as MGO. However, Cur-MGO adducts have not been studied in depth to date and it remains to be known whether Cur-MGO adducts are able to attenuate endothelial damage by trapping MGO. In the present study, 1,2-diaminobenzene was reacted with MGO to ensure the reliability of the reaction system. Cur was demonstrated to trap MGO at a 1:1 ratio to form adducts 1, 2 and 3 within 720 min. The structures of these adducts were identified by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. The kinetic curves of Cur (10(-7), 10(-6) and 10(-5) M) were measured from 0-168 h by fluorescent intensity. Cur significantly inhibited the formation of advanced glycation end products (AGEs). The differences in oxidative damage and the levels of pro-inflammatory cytokines following MGO + HSA or Cur-MGO treatment were investigated in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to the Cur-MGO reaction adducts significantly reduced the intracellular ROS levels and improved cell viability compared with MGO alone. Furthermore, there was a significant reduction in the expression levels of transforming growth factor-ß1 and intercellular adhesion molecule(-1) following treatment with Cur-MGO adducts compared with MGO alone. These results provide further evidence that the trapping of MGO by Cur inhibits the formation of AGEs. The current study indicates that the protective effect of Cur on carbonyl stress and pro-inflammatory responses in endothelial damage occurs via the trapping of MGO.


Assuntos
Curcumina/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , Aldeído Pirúvico/metabolismo , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Aldeído Pirúvico/química , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Zhongguo Zhong Yao Za Zhi ; 41(17): 3265-3271, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-28920381

RESUMO

According to the research strategy of resource chemistry of Chinese medicinal materials and Chinese medicinal resources recycling utilization, this study intends to explore the potential resource-oriented utilization value of the seed of Sophora flavescens by contrasting with its kindred plant S. alopecuroides. This study established a rapid UPLC-Q-TOF-MS/MS and UPLC-TQ-MS/MS method to determine the alkaloids in the seed of S. flavescens. Results of UPLC-Q-TOF-MS/MS analysis showed that the alkaloids in the seed of S. flavescens were highly similar with S. alopecuroides.In the determination of 7 kinds of alkaloids, the total content was 11.203 and 15.506 mg•g⁻¹ in the seed of S. flavescens and S. alopecuroides, respectively. The content of oxymatrine, oxysophocarpine and sophoridine is high in the seed of S. flavescens. The results indicated that the seeds of S. flavescens. could be an important material resource to obtain alkaloids.


Assuntos
Alcaloides/análise , Quinolizinas/análise , Sementes/química , Sophora/química , China , Compostos Fitoquímicos/análise , Espectrometria de Massas em Tandem
12.
Zhongguo Zhong Yao Za Zhi ; 41(3): 490-497, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28868869

RESUMO

To evaluate the nephrotoxicity of total terpenoids from Alismatis Rhizoma on human kidney proximal tubular cells (HK-2), explore the iraction in inducing apoptosis of HK-2 cells, and provide reference for the research of controversial nephrotoxicity of total terpenoids from Alismatis Rhizoma, HK-2 cells were used and cells viability was measured by MTT colorimetric method. An assessment of cells apoptosis was also conducted by using flow cytometry. Meanwhile western blot assay was used to detect the protein expressions of caspase-3, Bcl-2, Bcl-xl, Kim-1, clusterin and TFF-3. At last, q-PCR was used to detect the mRNA expressions of caspase-3, Bcl-2, Bcl-xl, Kim-1, clusterin and TFF-3. The flow cytometry results showed that cells apoptosis rate was (37.48±1.76)%, (26.91±1.91)% and (25.61±2.05)% respectively after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). Western blot results showed that Bcl-2 and Bcl-xl protein levels were significantly decreased after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹), while the protein expression of caspase-3 was significantly increased. q-PCR results were the same with western blot results, that mRNA expressions of Bcl-2 and Bcl-xl were significantly decreased while mRNA expression of caspase-3 was significantly increased after treating with total terpenoids (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). Western blot results and q-PCR results showed that both mRNA and protein expressions of Kim-1, clusterin and TFF-3 were significantly increased after treating with total terpenoids from Alismatis Rhizoma (6.25×10-5, 3.125×10-5, 1.562 5×10-5 g•mL⁻¹). HK-2 cells in vitro evaluation results showed that, total terpenoids from Alismatis Rhizoma may have nephrotoxicity effect, but further study is still needed for verification; meanwhile, they could induce HK-2 cells apoptosis, providing basis for nephrotoxicity study and safe application of Alismatis Rhizoma.


Assuntos
Alisma/química , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/toxicidade , Rim/efeitos dos fármacos , Terpenos/toxicidade , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clusterina/genética , Clusterina/metabolismo , Medicamentos de Ervas Chinesas/análise , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Receptor Celular 1 do Vírus da Hepatite A/genética , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Rim/citologia , Rizoma/química , Terpenos/análise
13.
Zhongguo Zhong Yao Za Zhi ; 40(13): 2496-502, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26697669

RESUMO

"Prescription embodied in Preparation", Chinese medicine preparation, aims to study the specific form of Chinese medicine from raw materials to preparation for acting on patients directly. Its development has gone through three stages according to the characteristics of raw materials pretreatment, including "direct smash and initial extraction for Chinese materia medica", "Extensive extraction and preliminarily impurity for Chinese materia medica" and "Refining and purification for Chinese materia medica". With the development of new technologies and new theories, Chinese medicine preparation emerged in a new stage: structural components of Chinese medicine, with the characteristics of definited material basis, clear mechanisms, determined ADME/T properties, reasonable drug release system designs and scientific productions quality controls. This requires multidisciplinary to solve systemly the problems of Chinese medicine preparation. In this article, we reviewed the development of Chinese medicine preparation in different times, and analyzed the development and the characteristics of Chinese medicine preparation; and mainly focused on a fact that multidisciplinary promoted the study and development of Chinese medicine preparation, especially in structural components of Chinese medicine. It provides development direction and theoretical basis for Chinese medicine preparation.


Assuntos
Medicina Tradicional Chinesa , Materia Medica/isolamento & purificação , Tecnologia Farmacêutica
14.
Mol Med Rep ; 12(6): 7992-8002, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26498639

RESUMO

The migration and invasion of lung cancer cells into the extracellular matrix contributes to the high mortality rates of lung cancer. The protein kinase C (PKC) and downstream signaling pathways are important in the invasion and migration of lung cancer cells. Calycosin (Cal), an effector chemical from Astragalus has been reported to affect the recurrence and metastasis of cancer cells via the regulation of the protein expression of matrix metalloproteinases (MMPs). The inhibition of Cal on the migration and invasion of A549 cells was investigated in the present study. Cell viability and apoptosis assays were performed using MTT and flow cytometric analyses. A wound healing assay and Transwell invasion assay were performed to evaluate the effect of Cal on A549 cell migration and invasion. Invasion­associated proteins, including MMP­2, MMP­9, E­cadherin (E­cad), integrin ß1, PKC­α and extracellular signal­regulated kinase 1/2 (ERK1/2) were detected using western blotting. In addition, PKC­α inhibitor, AEB071, and ERK1/2 inhibitor, PD98059, were used to determine the association between the suppression of PKC­α /ERK1/2 and invasion, MMP­2, MMP­9, E­cad and integrin ß1. Cal was observed to suppress cell proliferation and induce apoptosis. There were significant differences between the phorbol­12­myristate­13­acetate (TPA)­induced A549 cells treated with Cal and the untreated cells in the rates of migration and invasion. The levels of MMP­2, MMP­9, E­cad and integrin ß1 in the TPA­induced A549 cells changed markedly, compared with the untreated cells. In addition, the suppression of Cal was affected by the PKC inhibitor, AEB071, an ERK1/2 inhibitor, PD98059. The results of the present study indicated that Cal inhibited the proliferation, adhesion, migration and invasion of the TPA­induced A549 cells. The Cal­induced repression of PKC­α/ERK1/2, increased the expression of E­Cad and inhibited the expression levels of MMP­2, MMP­9 and integrin ß1, which possibly demonstrates the mechanism underlying the biological anticancer effects of Cal.


Assuntos
Proliferação de Células/efeitos dos fármacos , Isoflavonas/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase C-alfa/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Flavonoides/farmacologia , Humanos , Integrina beta1/metabolismo , Isoflavonas/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Ésteres de Forbol/farmacologia , Proteína Quinase C-alfa/antagonistas & inibidores , Pirróis/farmacologia , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Zhongguo Zhong Yao Za Zhi ; 40(4): 758-64, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26137704

RESUMO

Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi-channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM.


Assuntos
Tratamento Farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Interações Medicamentosas , Medicamentos de Ervas Chinesas/química , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa
16.
Zhongguo Zhong Yao Za Zhi ; 40(5): 840-6, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26087543

RESUMO

Alisma orientalis is a traditional herb medicine commonly used in clinical. With the increasing report of its toxicity in clinical, the renal toxicity of Alisma orientalis has got gradually attention. This paper systematically reviews the research on the chemical material basis of Alisma orientalis including its chemical composition and toxicity of ingredients; and also declares its toxic ingredients and targets according to Network toxicology. Based on the controversy on renal toxicity of Alisma orientalis, we analyzed the possible reasons that may be associated with renal toxicity. It might be associated with the differences of the material basis composition and regulatory toxicology network, differences in employed processing technology, the metabolic function leading to accumulation of compounds, dosage and duration of the experiment and compatibility. The review provides possible reference and ideas for the quality control and rational use of Alisma orientalis.


Assuntos
Alisma/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Alisma/toxicidade , Animais , Humanos , Estrutura Molecular
17.
Zhongguo Zhong Yao Za Zhi ; 40(5): 920-6, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26087557

RESUMO

OBJECTIVE: To study the effect of different composition structures of total paeony glycoside (TPG) component and total phenolic acid of Ligusticum chuanxiong ( TLPA) on sodium dithionite (Na2S2O4) -induced human umbilical vein endothelial cells (HUVEC) hypoxic injury. The baseline geometric proportion was used to design different components structure. And then the best structure of components by cell injury model were optimized. METHOD: A HUVEC hypoxic injury model was established by being induced of Na2S2O4. Cell viability was measured by MTI colorimetric method, intracellular superoxide dismutase (SOD) activity, malondialdehyde (MDA), lactate dehydrogenase( LDH) levels, nitric oxide (NO) contents were measured by kits. At last, Western blot analysis was used to detect the expression of two proteins, Bcl-2 and Bax. RESULT: Compared with the model group, TPG component, TLPA component at different composition structures can significantly increase SOD activity and decrease MDA, LDH, NO levels (P < 0.01, P < 0.05). Paeoniae Radix Rubra and Chuanxiong Rhizoma components can downregulate the expression of Bax protein and upregulate the expression of Bcl-2 protein. The ratio of Bcl-2 and Bax was significantly increased (P < 0 01, P < 0 05), it means that cell apoptosis was inhibited. The results indicate that among all the component composition structures, TPG and TLPA component at the proportion of 8: 2 had the best protection on hypoxic injury of endothelial cells. CONCLUSION: TPG component and TLPA component can resist HUVEC hypoxia injury, the protective effect was the most evident under the structure of 8: 2, which may be due to the inhibition of intracellular lipid peroxidation and cell apoptosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hipóxia/metabolismo , Paeonia/química , Rizoma/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hidroxibenzoatos/análise , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/fisiopatologia , Malondialdeído/metabolismo , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-26064167

RESUMO

Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41 ± 5.44%, 33.56 ± 4.85%, and 27.57 ± 4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-ß1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.

19.
J Pharm Pharmacol ; 67(8): 1143-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25880237

RESUMO

OBJECTIVES: Shikonin is an active naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon. This study was designed to explore the inhibition of Shikonin on cell viability, adhesion, migration and invasion ability of gastric cancer (GC) and its possible mechanism. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for cell viability and adhesion ability of MGC-803 cells. Cell scratch repair experiments were conducted for the determination of migration ability while transwell assay for cell invasion ability. Western blot analysis and real-time polymerase chain reaction assay were used for the detection of protein and mRNA expressions. KEY FINDINGS: Fifty per cent inhibitory concentration of Shikonin on MGC-803 cells was 1.854 µm. Shikonin (1 µm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells. Interestingly, Shikonin in the presence or absence of anti-Toll-like receptor 2 (TLR2) antibody (2 µg) and nuclear factor-kappa B (NF-κB) inhibitor MG-132 (10 µm) could decrease these ability of MGC-803 cells markedly, as well as the expression levels of matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB. In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone. CONCLUSIONS: The results indicated that Shikonin could suppress the cell viability, adhesion, invasion and migratory ability of MGC-803 cells through TLR2- or NF-κB-mediated pathway. Our findings provide novel information for the treatment of Shikonin on GC.


Assuntos
Antineoplásicos/farmacologia , NF-kappa B/metabolismo , Naftoquinonas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Receptor 2 Toll-Like/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lithospermum , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 7 da Matriz/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/fisiopatologia
20.
Mol Med Rep ; 12(1): 520-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25760137

RESUMO

The aim of the current study was to investigate the effects and mechanism of metformin in oxidative stress and p38 mitogen-activated protein kinase (p38MAPK) expression in rat glomerular mesangial cells (MCs) cultured in a high glucose medium. Rat glomerular MCs (HBZY-1) were cultured in complete medium and divided into the following five groups: Normal control (NC), high glucose (HG), metformin-treated, SB203580-treated (SB) and N-acetylcysteine-treated (NAC). The production of intracellular reactive oxygen species (ROS) in rat glomerular MCs was measured using flow cytometry. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the supernatant was detected using colorimetric analysis and an ELISA, respectively. p22phox mRNA levels in rat glomerular MCs were determined using reverse transcription-quantitative polymerase chain reaction. The levels of p22phox protein and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) protein in rat glomerular MCs were determined by western blot analysis. Compared with the NC group, the activity of SOD in the supernatant was significantly reduced, whereas the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs were significantly increased in the HG group (P<0.05). When metformin was added to the high glucose medium, the activity of SOD in supernatant fluid was increased significantly, whereas a significant reduction (P<0.05) was observed in the levels of MDA in the supernatant, intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS production in rat glomerular MCs. These results were similar to those obtained when SB203580 or N-acetylcysteine was added to the high glucose medium (P<0.05). In conclusion, metformin was suggested to alleviate high glucose-induced oxidative stress and p-p38MAPK protein expression in rat glomerular MCs, which may contribute to its reno­protective abilities in diabetes.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Metformina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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