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1.
Phytother Res ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026542

RESUMO

Cholestasis is a common manifestation of decreased bile flow in various liver diseases. It results in fibrosis and even cirrhosis without proper treatment. It is believed that a wide range of factors, including transporter dysfunction, oxidative stress, inflammatory damage, and immune disruption, can cause cholestasis. In recent years, natural products have drawn much attention for specific multiple-target activities in diseases. Many attempts have been made to investigate the anticholestatic effects of natural products with advanced technology. This review summarizes recent studies on the biological activities and mechanisms of recognized compounds for cholestasis treatment. Natural products, including various flavonoids, phenols, acids, quinones, saponins, alkaloids, glycosides, and so on, function as comprehensive regulators via ameliorating oxidative stress, inflammation, and apoptosis, restoring bile acid balance with hepatic transporters, and adjusting immune disruption. Moreover, in this progress, nuclear factor erythroid 2-related factor 2, reactive oxygen species production, heme oxygenase-1, NF-κB, cholesterol 7 alpha-hydroxylase, and farnesoid X receptors are thought as main targets for the activity of natural products. Therefore, this review presents the detailed mechanisms that include multiple targets and diverse signalling pathways. Natural products are the valuable when seeking novel therapeutic agents to treat cholestatic liver diseases.

2.
Life Sci ; 248: 117456, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097666

RESUMO

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologia
3.
J Cell Mol Med ; 24(7): 4036-4050, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32073745

RESUMO

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.

4.
J Pharm Pharmacol ; 72(2): 279-293, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31743450

RESUMO

OBJECTIVES: This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches. METHODS: Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR. KEY FINDINGS: ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e. CONCLUSIONS: The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

5.
Chin Med ; 14: 30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467589

RESUMO

Background: Astragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained. This study aims to investigate the mechanism of AR intervention in liver fibrosis based on comprehensive metabolomics combined with network pharmacology approach. Materials and methods: UPLC-Q-TOF/MS based metabolomics technique was used to explore the specific metabolites and possible pathways of AR affecting the pathological process of liver fibrosis. Network pharmacology analysis was introduced to explore the key targets of AR regarding the mechanisms on liver fibrosis. Results: AR significantly reduced the levels of ALT, AST and AKP in serum, and improved pathological characteristics. Metabolomics analysis showed that the therapeutic effect of AR was mainly related to the regulation of nine metabolites, including sphingosine, 6-keto-prostaglandin F1a, LysoPC (O-18:0), 3-dehydrosphinganine, 5,6-epoxy-8,11,14-eicosatrienoic acid, leukotriene C4, taurochenodesoxycholic acid, LysoPC (18:1 (9Z)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine. Pathway analysis indicated that the treatment of AR on liver fibrosis was related to arachidonic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Validation of the key targets by network pharmacology analysis of potential metabolic markers showed that AR significantly down-regulated the expression of CYP1B1 and up-regulated the expression of CYP1A2 and PCYT1A. Conclusion: Metabolomics combined with network pharmacology was used for the first time to clarify that the treatment of AR on liver fibrosis, which is related to the regulation of arachidonic acid metabolism and ether lipid metabolism by modulating the expression of CYP1A2, CYP1B1 and PCYT1A. And the integrated approach can provide new strategies and ideas for the study of molecular mechanisms of traditional Chinese medicines in the treatment of liver fibrosis.

6.
AMB Express ; 9(1): 101, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297618

RESUMO

Antibiotics abuse has caused increased bacterial resistance, which severely limits the application of antibiotics to the treatment of bacterial infections. Therefore, it is urgent to develop new antibacterial drugs through other sources. Dracontomelon dao (Blanco) Merr. & Rolfe (Ren Mianzi in Chinese) is a traditional medicinal material derived from Anacardiaceae with a long history of treating various infectious diseases, such as decubitus and skin ulcers. Recent research has indicated that different extracts from the leaves of D. dao, especially the ethyl acetate (EtOAc) fraction containing flavonoids and phenolic acids, exhibit potent antibacterial activities. In this research, the combined anti-drug-resistant bacterial activities of these active ingredients were investigated. Six samples (S1-S6) were obtained from the EtOAc fraction of D. dao leaves. Microcalorimetric measurements and principal component analysis were performed on the in vitro samples. The results showed that all six samples had notable antibacterial activities. Specifically, sample S6 exhibited a prominent antibacterial effect, with an IC50 value of 84.3 µg mL-1, which was significantly lower than that of other samples. The relative contents of main flavonoids and phenolic acids in S6 sample were confirmed by UPLC/Q-TOF-MS. In conclusion, sample S6 from the EtOAc fraction of D. dao leaves could be used as a potential antimicrobial resource in the treatment of infectious diseases. This work provides an insight into the effect of traditional Chinese medicine on drug-resistant bacteria. Moreover, the purification and characterization of the chemical compounds from the sample S6 deserve further analysis.

8.
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
9.
J Ethnopharmacol ; 238: 111880, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31004728

RESUMO

BACKGROUND: The combined use of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) are classic compatibilities in China for the treatment of cardiovascular diseases such as increasing myocardial contractility, anti-arrhythmia, reducing myocardial oxygen consumption, and dilating organ blood vessels, etc, thereby exerting anti-heart failure (HF) effects in traditional Chinese herbal medicine. However, comprehensive approaches for understanding the therapeutic effects and mechanisms underlying chronic heart failure (CHF) from the perspective of energy metabolism have not been pursued. AIM: This research was aimed to investigate the effectiveness and potential mechanism of ALRP combined with ZR (1:1) on doxorubicin (DOX)-induced CHF in rats based on an integrated approach that combines network pharmacology analyses and molecular biology. MATERIAL AND METHODS: CHF model was established by the intraperitoneal injection of DOX. ALRP and ZR were intragastrically administrated for three weeks. The detection indices including hemodynamic measurements, myocardial injury marker, and myocardial pathological changes were measured. Network pharmacology analysis was used to illustrate the pathways and network of ALRP and ZR against HF. Mitochondrial energy metabolism pathway associated gene and protein levels of PPARα, PGC-1α and Sirt3 in myocardial tissue were detected by real-time PCR and western blotting, respectively. RESULTS: The results indicated that ALRP-ZR herbal couple significantly improved the left ventricular function and cardiac enzyme activities in comparison with their single use. Network pharmacology analysis results showed that the pharmacological mechanisms of ALRP-ZR may be related to PPAR energy metabolism pathway. Besides, the outcomes of western-blot and real-time PCR analysis showed that ALRP-ZR significantly upregulates the protein and gene level of PPARα, PGC-1α, and Sirt3. CONCLUSIONS: Network pharmacology analysis would be an effective network analyze workflow which was feasible for evaluating the pharmacological effect of a multi-drug complex system. The Chinese herbal couple ALRP-ZR had a better therapeutic effect than their single-use against DOX-induced CHF, which may be related to enhancing left ventricular function by activating the PPARα/PGC-1α/Sirt3 pathway.


Assuntos
Aconitum/química , Doxorrubicina/toxicidade , Insuficiência Cardíaca/induzido quimicamente , Rizoma/química , Zingiberaceae/química , Animais , Biomarcadores , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/prevenção & controle , Masculino , 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 , Ratos , Ratos Sprague-Dawley , Sirtuínas/genética , Sirtuínas/metabolismo , Inibidores da Topoisomerase II/toxicidade
10.
J Ethnopharmacol ; 238: 111838, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30930257

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sancao granule (SCG) is a traditional Chinese herb formula, which has been used for autoimmune liver disease for decades. Previous study demonstrated that there was an exactly therapeutic effect of SCG on autoimmune hepatitis (AIH) by improving liver function and alleviating the clinical symptoms. However, studies of the mechanism by which SCG alleviates Con A-induced liver injury (CILI) should be complemented. MATERIALS AND METHODS: An ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach combined with principle component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) were integrated applied to obtain metabolites for clarifying mechanisms of disease. RESULTS: In accordance with previously study, the present study demonstrated that SCG could obviously improve the liver injury in mouse induced by Con A via downregulating serum biochemical indexes, alleviating the histological damage and inhibiting the neutrophil infiltration in liver tissues. Different expression of 9 metabolites related to 8 pathways, including fatty acid biosynthesis, arachidonic acid metabolisms, linoleic acid metabolisms, sphingolipid metabolisms, fatty acid elongation in mitochondria, glycerophospholipid metabolism, fatty acid metabolism, pyrimidine metabolism were demonstrated responsible for the efficacy of SCG in treating CILI. CONCLUSION: In sum up, SCG has been indicated favorable therapeutic effect on Con A induced liver injury. And metabolomics could be a promising approach, which provide insights into mechanisms of SCG in treating CILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Concanavalina A , Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Substâncias Protetoras/farmacologia
11.
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
12.
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
13.
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.

14.
J Pharm Pharmacol ; 70(12): 1675-1687, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277564

RESUMO

OBJECTIVES: Cholestasis is a critical risk factor for severe hepatic disease or cirrhosis. The anti-inflammatory effect of Paeonia lactiflora Pall. (PLP), named Chishao in traditional Chinese medicine (TCM), on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model was tried to be elucidated in this research. METHODS: Therapeutic effect indices on hepatic function, including ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT, were measured. To further investigate the protective mechanism of PLP, the mRNA and protein expression levels of NF-κB-NLRP3 inflammasome pathway were detected. RESULTS: Our results showed that compared with the model group, PLP could significantly reduce the increased serum indices such as ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT induced by ANIT in a dose-dependent way. Moreover, we found that PLP downregulated the mRNA expression levels including IKK, p65, NLRP3, caspase-1 and IL-1ß, especially at the large dose. Furthermore, PLP also significantly inhibited NF-κB-NLRP3 inflammasome pathway by decreasing the protein levels of p65, p-p65, p-IKK, NLRP3, caspase-1 and IL-1ß. CONCLUSIONS: The results indicated that PLP could ameliorate ANIT-induced cholestasis in rats and the anti-inflammatory effect of PLP might be related to regulating NF-κB-NLRP3 inflammasome pathway. This study will provide scientific evidence for PLP as a potential drug candidate for cholestasis.


Assuntos
Inflamassomos/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/biossíntese , Paeonia , Extratos Vegetais/farmacologia , 1-Naftilisotiocianato/farmacologia , Animais , Biomarcadores , Colestase/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Testes de Função Hepática , Medicina Tradicional Chinesa , RNA Mensageiro , Ratos , Ratos Sprague-Dawley
15.
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.

16.
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.

17.
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.

18.
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.

19.
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
20.
Chin J Integr Med ; 24(7): 502-511, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26688180

RESUMO

OBJECTIVE: To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis. METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor ß1 (TGF-ß1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase. RESULTS: Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-ß1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01). CONCLUSION: SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-ß1/Smad signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteína HMGB1/metabolismo , Cirrose Hepática/tratamento farmacológico , Proteínas Smad/metabolismo , Animais , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
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