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1.
Front Pharmacol ; 10: 1356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780949

RESUMO

The health supplement of Rhodiola crenulata (RC) is well known for its effective properties against hypoxia. However, the mechanisms of its anti-hypoxic action were still unclear. The objective of this work was to evaluate the molecular mechanisms of RC extract against hypoxia in a hypoxic zebrafish model through metabonomics and network pharmacology analysis. The hypoxic zebrafish model in the environment with low concentration (3%) of oxygen was constructed and used to explore the anti-hypoxic effects of RC extract, followed by detecting the changes of the metabolome in the brain through liquid chromatography-high resolution mass spectrometry. An in silico network for metabolite-protein interactions was further established to examine the potential mechanisms of RC extract, and the mRNA expression levels of the key nodes were validated by real-time quantitative PCR. As results, RC extract could keep zebrafish survive after 72-h hypoxia via improving lactate dehydrogenase, citrate synthase, and hypoxia-induced factor-1α in brains. One hundred and forty-two differential metabolites were screened in the metabonomics, and sphingolipid metabolism pathway was significantly regulated after RC treatment. The constructed protein-metabolites network indicated that the HIF-related signals were recovered, and the mRNA level of AMPK was elevated. In conclusion, RC extract had markedly anti-hypoxic effects in zebrafish via changing sphingolipid metabolism, HIF-related and AMPK signaling pathways.

2.
Front Microbiol ; 10: 1398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316482

RESUMO

Although the biological processes of organism under hypoxic stress had been elucidated, the whole physiological changes of Saccharomyces cerevisiae are still unclear. In this work, we investigated the changes of biological process of S. cerevisiae under hypoxia by the methods of transcriptomics, proteomics, metabolomics, and bioinformatics. The results showed that the expression of a total of 1017 mRNA in transcriptome, 213 proteins in proteome, and 51 metabolites in metabolome had been significantly changed between the hypoxia and normoxia conditions. Moreover, based on the integration of system-omics data, we found that the carbohydrate, amino acids, fatty acid biosynthesis, lipid metabolic pathway, and oxidative phosphorylation were significantly changed in hypoxic stress. Among these pathways, the glycerophospholipid metabolic pathway was remarkably up-regulated from the mRNA, protein, and metabolites levels under hypoxic stress, and the expression of relevant mRNA was also confirmed by the qPCR. The metabolites of glycerophospholipid pathway such as phosphatidylcholine, phosphatidylethanolamine, phosphoinositide, and phosphatidic acids probably maintained the stability of cell membranes against hypoxic stress to relieve the cell injury, and kept S. cerevisiae survive with energy production. These findings in the hypoxic omics and integrated networks provide very useful information for further exploring the molecular mechanism of hypoxic stress.

4.
Mol Genet Genomics ; 294(5): 1159-1171, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31053932

RESUMO

Li-Ru-Kang (LRK) has been commonly used in the treatment of hyperplasia of mammary gland (HMG) as a cipher prescription and achieved obvious therapeutic effects. However, the bioactive compounds and underlying pharmacological mechanisms remain unclear. This study aims to decipher the bioactive compounds and potential action mechanisms of LRK in the treatment of HMG using an integrated pharmacology approach. The ingredients of LRK and the corresponding drug targets were retrieved through drug target databases and were used to construct the "compound-target-disease" network and function-pathway network. Ultimately, 89 compounds and 2150 drug targets were collected. Gene ontology enrichment analysis revealed that mammary gland alveolus development and mammary gland lobule development were the key biological processes and were regulated simultaneously by three direct targets, including androgen receptor (AR), estrogen receptor (ER) and cyclin-D1. Moreover, 14 compounds of LRK were directly involved in the regulation of the three aforementioned targets. KEGG pathway enrichment analysis found that five signaling pathways and seven direct targets were closely related with HMG treatment by LRK. The results of animal experiments showed that LRK significantly improved the histopathological status of HMG in rats. Additionally, LRK markedly regulated the protein expressions of AR, cyclin-D1, MMP2, MMP3 and MMP9. But interestingly, the effect of LRK on ER was not obvious. This study demonstrated that LRK exerted its therapeutic efficacy based on multi-components, multi-targets and multi-pathways. This research confirms the advantages of network pharmacology analyses and the necessity for experimental verification.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hiperplasia/tratamento farmacológico , Glândulas Mamárias Animais/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Feminino , Medicina Tradicional Chinesa/métodos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
5.
Front Pharmacol ; 10: 242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941037

RESUMO

Agomelatine (AGO) is a new type of antidepressant with demonstrated antidepressant effects and a unique modulating circadian rhythm action. However, AGO has hepatotoxicity, which limits its clinical application. In order to develop new drugs that cause less liver injury than AGO, a series of derivatives were synthesized; compound GW117 was screened from derivatives due to its high receptor affinity. This study will investigate its sub-acute oral toxicity profile in rats in a sex-dependent manner. GW117 and AGO was administrated by gavage (200, 400, or 800 mg/kg/day) for 28 days. Hematological, biochemical tests, organ weights, histopathological examinations were carried out, the results showed that AGO and GW117 had adverse effects on platelet, liver and kidney, and had sex-differences in some indicators. Hematological tests showed that AGO and GW117 reduced the platelet count in male animals but had no effect in females. AGO increased plasma alanine aminotransferase (ALT) and total bilirubin in male animals, and GW117 had no effect on these two indicators. For females, AGO moderately elevated ALT, alkaline phosphatase (ALP), and total bilirubin, while GW117 only elevated ALP slightly. Two drugs could increase liver weight and coefficient, and cause liver pathological injury, including hepatic sinusoidal dilatation, hepatocyte fatty deposition and dotted cell necrosis in two genders. AGO caused mild to moderate hepatocyte and hepatobiliary injury in both genders, while only a mild hepatobiliary injury was caused by GW117 in females. Renal function tests showed that both drugs can increase blood urea nitrogen levels in males, while AGO, but not GW117, can slightly increase blood creatinine and urea nitrogen in females. The kidney weight and coefficient could be significantly increased by two drugs in males, and by AGO medium and GW117 high and low doses in females. The kidney pathological damage was mainly characterized by tubule dilatation, a thinning of the renal cortex. Kidney damage caused by GW117 was less than that of AGO, and there was no sex-difference. In summary, GW117 can cause mild liver and kidney damage in both genders, as well as mild platelets reduction in males, while degree of damage is less severe than AGO. Therefore, as an excellent derivative, GW117 deserves further development as an antidepressant.

6.
Biomed Pharmacother ; 115: 108881, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028997

RESUMO

Higenamine (HG) is a well-known selective activator of beta2-adrenergic receptor (ß2-AR) with a positive inotropic effect. The present study showed that HG combined with [6]-gingerol (HG/[6]-GR) protects H9c2 cells from doxorubicin (DOX)-induced mitochondrial energy metabolism disorder and respiratory dysfunction. H9c2 cells were pretreated with HG/[6]-GR for 2 h before DOX treatment in all procedures. Cell viability was quantified by a cell counting kit­8 assay. Cardiomyocyte morphology, proliferation, and mitochondrial function were detected by a high content screening (HCS) assay. Cell mitochondrial stress was measured by a Seahorse XFp analyzer. To further investigate the protective mechanism of HG/[6]-GR, mRNA and protein expression levels of PPARα/PGC-1α/Sirt3 pathway-related molecules were detected. The present data demonstrated that protective effects of HG/[6]-GR combination were presented in mitochondria, which increased cell viability, ameliorated DOX-induced mitochondrial dysfunction, increased mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Most importantly, the protective effects were abrogated by GW6471 (a PPARα inhibitor) and ameliorated by Wy14643 (a PPARα agonist). Moreover, the combined use of HG and [6]-GR exerted more profound protective effects than either drug as a single agent. In conclusion, the results suggested that HG/[6]-GR ameliorates DOX-induced mitochondrial energy metabolism disorder and respiratory function impairment in H9c2 cells, and it indicated that the protective mechanism may be related to upregulation of the PPARα/PGC-1α/Sirt3 pathway, which promotes mitochondrial energy metabolism and protects against heart failure.


Assuntos
Alcaloides/farmacologia , Catecóis/farmacologia , Doxorrubicina/toxicidade , Álcoois Graxos/farmacologia , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Tetra-Hidroisoquinolinas/farmacologia , Translocador 1 do Nucleotídeo Adenina/genética , Translocador 1 do Nucleotídeo Adenina/metabolismo , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Alcaloides/administração & dosagem , Animais , Antibióticos Antineoplásicos/toxicidade , Catecóis/administração & dosagem , Linhagem Celular , Sobrevivência Celular , Metabolismo Energético/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Sirtuínas/genética , Sirtuínas/metabolismo , Tetra-Hidroisoquinolinas/administração & dosagem , Fatores de Transcrição de p300-CBP/genética , Fatores de Transcrição de p300-CBP/metabolismo
7.
Sci Rep ; 9(1): 2000, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760797

RESUMO

To compare and evaluate the differences of stereoselective activity, the binding affinity, metabolism, transport and molecular docking of phencynonate isomers to muscarinic acetylcholine receptor (mAChR) were investigated in this study. The rotation stimulation and locomotor experiments were used to evaluate anti-motion sickness effects. The competitive affinity with [3H]-QNB and molecular docking were used for studying the interactions between the two isomers and mAChR. The stereoselective mechanism of isomers was investigated by incubation with rat liver microsomes, a protein binding assay and membrane permeability assay across a Caco-2 cell monolayer using a chiral column HPLC method. The results indicated that S-isomer was more effective against motion sickness and had not anxiogenic action at therapeutic doses. S-isomer has the higher affinity and activity for mAChR in cerebral cortex and acted as a competitive mAChR antagonist. The stereoselective elimination of S-isomer was primarily affected by CYP1B1 and 17A1 enzymes, resulting in a higher metabolic stability and slower elimination. Phencynonate S isomer, as a eutomer and central anticholinergic chiral drug, is a novel anti-motion sickness drug with higher efficacy and lower central side effect. Our data assisted the development of a novel drug and eventual use of S-isomer in clinical practice.

8.
Mini Rev Med Chem ; 19(2): 125-137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30332952

RESUMO

Infectious diseases caused by pathogenic bacteria seriously threaten human lives. Although antibiotic therapy is effective in the treatment of bacterial infections, the overuse of antibiotics has led to an increased risk of antibiotic resistance, putting forward urgent requirements for novel antibacterial drugs. Traditional Chinese herbal medicine (TCHM) and its constituents are considered to be potential sources of new antimicrobial agents. Currently, a series of chemical compounds purified from TCHM have been reported to fight against infections by drug-resistant bacteria. In this review, we summarized the recent findings on TCHM-derived compounds treating drug-resistant bacterial infections. Further studies are still needed for the discovery of potential antibacterial components from TCHM.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/uso terapêutico , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fenóis/uso terapêutico , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Terpenos/uso terapêutico
9.
Front Pharmacol ; 9: 1318, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524280

RESUMO

Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen the potential targets and possible pathways that involved in LRK treated HMG. Rat HMG model induced by estrogen and progesterone was used to further verify the effects of the key molecules of LRK selected from the enriched pathways on HMG. Nipple heights and diameters were measured and uterus index was calculated. The histopathological changes of mammary gland tissue were detected by hematoxylin-eosin (H&E) staining. Western blot was used to detect the phosphorylation of ERK, JNK, and P38. And immunohistochemistry staining was performed to evaluate the levels of estrogen receptor α (ERα), progesterone receptor (PR), nuclear factor-(NF-)κB (p65), interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), cyclooxygenases 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2'deoxyguanosine (8-OHdG), and nitrotyrosine (NT). Our results indicate that LRK treatment rescues significantly nipples height and diameter, decreases uterus index and ameliorates HMG. LRK treatment also markedly attenuates the over-expression of IL-1ß, TNF-α, COX-2, and iNOS, and suppressed the formation of 8-OHdG and NT. Furthermore, LRK treatment significantly inhibits the phosphorylation of JNK, ERK, and p38 and expression of NF-κB (p65), interestingly, LRK treatment has no effect on the expression of ERα and PR. Our data suggest that the LRK treatment protects the mammary glands from the damage of oxidative stress and inflammation induced by estrogen and progesterone, via suppresses of MAPK/NF-κB signaling pathways without affecting on the expression of ERα and PR.

10.
Front Pharmacol ; 9: 810, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30140225

RESUMO

Background: Chronic heart failure (CHF) is one of the most stubborn cardiovascular disease. Xinmailong (XML), a bioactive fraction extracted from Periplaneta americana L., has been commonly used for CHF treatment in China. However, there is few comprehensive evaluation for the clinical efficacy and safety of XML for CHF. Objectives: We aimed to evaluate the beneficial and adverse effects of Xinmailong Injection (XMLI) on CHF treatment with the use of meta-analysis. Methods: In accordance with the Cochrane Handbook and transparent reporting of systematic reviews and meta-analysis protocol (CRD42018087091), seven English and Chinese electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP medicine information system and China Biomedical Literature Database (CBM), were searched to retrieve potential randomized controlled trials (RCTs) before November 2017. The eligible trials were evaluated for methodological quality. The main outcome measures were analyzed with RevMan 5.3 software. Results: 26 RCTs involving 3447 participants were subjected to meta-analysis. The total effective rate was improved by XMLI plus conventional therapy (OR 3.10, 95% CI 2.47-3.90, P < 0.00001). When compared to the conventional treatment alone, the combination of XMLI and conventional treatment increased left ventricular ejection fraction (LVEF, MD 4.93, 95% CI 3.96-5.89, P < 0.00001) and 6-min walking distance (6-MWD, MD 46.76, 95% CI 32.51 to 61.01, P < 0.00001), and decreased left ventricular end-diastolic diameter (LVEDD, MD -4.73, 95% CI-5.64 to-3.83, P < 0.00001), serum brain natriuretic peptide (BNP, MD -149.59, 95% CI -211.31 to -87.88, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP, MD -322.35, 95% CI -517.87 to -126.83, P = 0.001). However, the frequency and severity of adverse effects was similar between these two different medications. Poor methodological quality and the limitations also existed in this study. Conclusions: The combinational use of XMLI on conventional treatment may exert better therapeutic effects on improving cardiac function in CHF patients, indicating that XMLI was suggested to be considered during the conventional treatment of CHF. High-quality and large scale RCTs are still required to confirm the impacts of XMLI.

11.
Front Pharmacol ; 9: 651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29971006

RESUMO

Background: Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses. Methods: The effects of LRK on HMG induced by estrogen-progesterone in rats were evaluated by analyzing the morphological and pathological characteristics of breast tissues. Moreover, UPLC-QTOF/MS was performed to explore specific metabolites potentially affecting the pathological process of HMG and the effects of LRK. Pathway analysis was conducted with a combination of metabolomics and network pharmacology analyses to illustrate the pathways and network of LRK-treated HMG. Results: Li-Ru-Kang significantly improved the morphological and pathological characteristics of breast tissues. Metabolomics analyses showed that the therapeutic effect of LRK was mainly associated with the regulation of 10 metabolites, including prostaglandin E2, phosphatidylcholine, leukotriene B4, and phosphatidylserine. Pathway analysis indicated that the metabolites were related to arachidonic acid metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Moreover, principal component analysis showed that the metabolites in the model group were clearly classified, whereas the metabolites in the LRK group were between those in the normal and model groups but closer to those in the normal group. This finding indicated that these metabolites may be responsible for the effects of LRK. The therapeutic effect of LRK on HMG was possibly related to the regulation of 10 specific metabolites. In addition, we further verified the expression of protein kinase C alpha (PKCα), a key target predicted by network pharmacology analysis, and showed that LRK could significantly improve the expression of PKCα. Conclusion: Our study successfully explained the modulatory properties of LRK treatment on HMG using metabolomics and network pharmacology analyses. This systematic method can provide methodological support for further understanding the complex mechanism underlying HMG and possible traditional Chinese medicine (TCM) active ingredients for the treatment of HMG.

12.
Front Pharmacol ; 9: 624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946260

RESUMO

Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury. Methods: In order to screen active components and predicate mechanisms of action, an "ingredients-target-disease" interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice. Results: This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3ß-acetyl-20,25-epoxydammarane-24α, and δ-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL. Conclusion: The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.

13.
Front Pharmacol ; 9: 45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29456506

RESUMO

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09-4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28-0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72-2.71; P < 0.00001) and decrease the size of breast lump (MD: -0.67; 95% CI: -0.86 to -0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH.

14.
Phytother Res ; 32(5): 757-768, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29235181

RESUMO

Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV-related cirrhosis as an adjuvant treatment. However, the efficacy of FZHY capsule for HBV-induced cirrhosis did not be comprehensively proved by systematic analysis. Our current analysis was aimed to assess the efficacy and safety of FZHY capsule by an evidence-based method. Databases, including China National Knowledge Infrastructure, Wangfang, VIP medicine information system, Pubmed, Embase, and Cochrane Library, were searched, and the randomized controlled trials of FZHY capsule were used for the treatment of HBV-associated liver cirrhosis. Meta-analysis was performed by Review Manager 5.3. The efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), Collagen C Type IV (IV-C), Child-Pugh score, portal vein diameter, spleen thickness, HBeAg negative conversion rate, and HBV-DNA negative conversion rate were systematically assessed. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Nineteen studies with 1,769 patients were included in the meta-analysis. Compared to conventional treatment, FZHY capsule was effective by increasing the efficacy. FZHY capsule was more efficient in improving ALT, AST, TBIL, PIIIP, HA, LN, IV-C, Child-Pugh grading score, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. Nevertheless, a variety of well-designed randomized controlled trials are needed to confirm these findings since small samples were applied in the previous studies.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Cápsulas , China , Terapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Vírus da Hepatite B/fisiologia , Humanos , Resultado do Tratamento
15.
Sci Rep ; 7(1): 15549, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29138445

RESUMO

Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. The in vitro NA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50 = 112.6 µg/ml; Ki = 55.6 µg/ml) in a competitive mode. The IC50 values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96.1 µg/ml; Phellodendri Chinensis Cortex, 108.6 µg/ml; Scutellariae Radix, 303.5 µg/ml; Gardeniae Fructus, 285.0 µg/ml. Thirteen compounds found in the plasma profile of HLJDT were also identified as potent NA-1 inhibitors, which included jatrorrhizine, palmatine, epiberberine, geniposide, oroxylin A, berberine, coptisine, baicalein, wogonoside, phellodendrine, wogonin, oroxylin A-7-O-glucuronide and baicalin (sorted in ascending order by their IC50 values). Their inhibitory activities were consistent with molecular docking analysis when considering crystallographic water molecules in the ligand-binding pocket of NA-1. Our current findings suggested that HLJDT can be used as a complementary medicine for H1N1 infection and its potent active compounds can be developed as NA-1 inhibitors.


Assuntos
Medicamentos de Ervas Chinesas/química , Inibidores Enzimáticos/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Neuraminidase/química , Animais , Berberina/análogos & derivados , Berberina/química , Alcaloides de Berberina/química , Cristalografia , Medicamentos de Ervas Chinesas/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Flavanonas/química , Gardenia/química , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Neuraminidase/antagonistas & inibidores , Ratos , Scutellaria baicalensis/química
16.
Biomed Pharmacother ; 96: 246-255, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28987949

RESUMO

Aconiti Lateralis Radix Praeparata (Fuzi), a type of Chinese materia medica, has been used to treat acute and chronic heart failure (HF) in traditional Chinese medicine and has been proven in numerous animal studies. It is also well-known that Zingiberis Rhizoma (Ganjiang) is ineffective in the treatment of HF, but it can enhance the anti-HF effect of Fuzi. However, the mechanism underlying this compatibility is still not well investigated. To investigate this mechanism, a model of acute heart failure (AHF) in SD rats induced by propafenone hydrochloride was established in this study. After oral treatments of Ganjiang, Fuzi or a combination of the two drugs in rats with AHF, heart function [e.g., heart rate (HR) and the maximal rising and declining rate of left ventricle pressure (±dp/dtmax)] and serum indicators [e.g., brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and creatine kinase (CK)] were measured, and histopathological analysis of the heart was also performed. The biological mechanisms were further explored by measuring the protein expression level of the mitochondrial respiration chain complex (MRCC1-4) and the mRNA and protein expression levels of mitochondrial Ca2+ uniporter (MCU) and its upstream proteins, mitochondrial Ca2+ uniporter 1 and mitochondrial Ca2+ uniporter 2 (MICU1-2). The expression levels of key enzymes downstream of the tricarboxylic acid cycle, including pyruvate dehydrogenase (PDH), malate dehydrogenase (MDH) and nicotinamide nucleotide transhydrogenase (NNT), were also measured. As a result, Ganjiang enhanced the therapeutic effect of Fuzi on AHF by raising the HR and ±dp/dtmax; decreasing the serum levels of BNP, LDH and CK; and alleviating histological damage of the myocardial tissue when compared to the treatments of Ganjiang or Fuzi alone. In conclusion, there was an enhancing effect of Ganjiang on the anti-AHF function of Fuzi treatment, and the potential mechanism of this effect may be related to the mitochondrial energy metabolism pathway mediated by MCU.


Assuntos
Aconitum , Insuficiência Cardíaca/tratamento farmacológico , Magnoliopsida , Extratos Vegetais/uso terapêutico , Rizoma , Doença Aguda , Animais , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/patologia , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
17.
Biomed Pharmacother ; 92: 651-660, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28578259

RESUMO

Aconiti Lateralis Radix Praeparata ("Fuzi" in Chinese) in combination with Zingiberis Rhizoma ("Ganjiang" in Chinese) is commonly applied for the treatment of heart failure for thousands of years in China. However, its therapeutic mechanism is still poorly defined. This study aimed to investigate whether the compatibility of Fuzi and Ganjiang can protect rats with acute heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α signaling pathway. Hemodynamic parameters, including heart rate and left ventricular maximal rate of pressure rise and decline, were recorded in rats with acute heart failure induced by Propafenone hydrochloride. The serum levels of cardiac enzymes, including creatine kinase, lactate dehydrogenase, brain natriuretic peptide and cardiac troponin T, were also determined. The gene and protein levels of Sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and their downstream transcription factors were measured as well. The results indicated that Fuzi-Ganjiang herbal couple provided more significant benefits by restoring the left ventricular function and cardiac enzyme activities in comparison with their single use. Moreover, this herbal couple possessed a significant cardio-protection by increasing both gene and protein levels of Sirt1 and PGC-1α. In conclusion, the compatibility of Fuzi and Ganjiang had better therapeutic effect than their single use against failing heart, and the underlying mechanisms were partially through increasing mitochondrial biogenesis via Sirt1/PGC-1α pathway.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/metabolismo , Magnoliopsida , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/biossíntese , Sirtuína 1/biossíntese , Animais , Cardiotônicos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/prevenção & controle , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
Exp Ther Med ; 13(3): 1032-1038, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28450937

RESUMO

Although Radix Achyranthis Bidentatae (RAB) and Radix Cyathulae (RC) are from two different medicinal plants, they are both used as 'Niu-Xi', a widely used traditional Chinese medicine that is believed to stimulate menstruation and affect bone injury. Angiogenesis is actively involved in treating these illnesses. The aim of the present study was to investigate whether the whole extracts of RAB and RC possess pro-angiogenic effects. In order to examine this idea whole extracts of RAB and RC were extracted with boiling water followed by ethanol, respectively. Results from the MTT, wound healing and tube formation assays in human umbilical vein endothelial cells (HUVECs) in vitro revealed that the whole extracts of RAB and RC did not increase cell proliferation or tube formation, but enhanced cell migration. Their angiogenic effects were also confirmed in zebrafish in vivo via increasing the sprout numbers in the sub-intestinal vessel. As determined by quantitative polymerase chain reaction, the whole extracts of RAB and RC both regulated the expression of cell migration-related genes in zebrafish. It is concluded that the whole extracts of RAB and RC induced angiogenesis in HUVECs in vitro and in zebrafish in vivo via increasing cell migration.

19.
Biomed Pharmacother ; 89: 61-68, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28214689

RESUMO

Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1ß (IL-1ß) and the hepatocyte transporters such as Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1ß induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2.


Assuntos
Proteínas de Transporte/metabolismo , Colestase/tratamento farmacológico , Glucosídeos/farmacologia , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fígado/metabolismo , Monoterpenos/farmacologia , 1-Naftilisotiocianato , Animais , Bile/química , Bile/metabolismo , Biomarcadores/sangue , Colestase/sangue , Colestase/metabolismo , Edema/induzido quimicamente , Edema/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Masculino , NF-kappa B/metabolismo , Necrose , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Zhen Jiu ; 37(10): 1061-5, 2017 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-29354974

RESUMO

OBJECTIVE: To investigate the effect and safety of acupuncture with regulating menstruation to promote pregnancy for diminished ovarian reverse (DOR). METHODS: According to prospective case series, 46 patients were observed and finally 40 cases were included. The acupoints were ① Baihui (GV 20), Shenting (GV 24), Guanyuan (CV 4) and bilateral Benshen (GB 13), Huangshu (KI 16), Dahe (KI 12), Luanchao (Extra), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3) and ② bilateral Shenshu (BL 23) and Ciliao (BL 32). The points in the two groups were used alternately. Acupuncture was given for 3 courses, 12 times as a course and 3 times a week. Before and after treatment, and 3 months after treatment, follicle-stimulating hormone (FSH), follicle-stimulating hormone/luteinizing hormone (FSH/LH), estradiol (E2), antral follicle count (AFC) and TCM symptom score were observed. The safety was evaluated. RESULTS: Compared with before treatment, the levels of FSH, FSH/LH decreased, and the levels of E2 and AFC increased after treatment and at follow-up (all P<0.05). And the TCM symptom scores were significantly lower than those before treatment (both P<0.05). The rate of pregnancy after treatment was 15% (6/40). There was no infection and organ injury. CONCLUSION: Acupuncture with regulating menstruation to promote pregnancy can safely improve the ovarian reserve of patients with DOR.


Assuntos
Terapia por Acupuntura/métodos , Menstruação , Reserva Ovariana/fisiologia , Pontos de Acupuntura , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Gravidez , Estudos Prospectivos
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