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1.
J Ethnopharmacol ; 279: 114371, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181957

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diterpene Ginkgolides Meglumine Injection (DGMI) is made of extracts from Ginkgo biloba L, including Ginkgolides A, B, and K and some other contents, and has been widely used as the treatment of cerebral ischemic stroke in clinic. It can be learned from the "Compendium of Materia Medica" that Ginkgo possesses the effect of "dispersing toxin". The ancient Chinese phrase "dispersing toxin" is now explained as elimination of inflammation and oxidative state in human body. And it led to the original ideas for today's anti-oxidation studies of Ginkgo in apoptosis induced by optic nerve crush injury. AIM OF THE STUDY: To investigate the underlying molecular mechanism of the DGMI in retinal ganglion cells (RGCs) apoptosis. MATERIALS AND METHODS: TUNEL staining was used to observe the anti-apoptotic effects of DGMI on the adult rat optic nerve injury (ONC) model, and flow cytometry and hoechst 33,342 staining were used to observe the anti-apoptotic effects of DGMI on the oxygen glucose deprivation (OGD) induced RGC-5 cells injury model. The regulation of apoptosis and MAPKs pathways were investigated with Immunohistochemistry and Western blotting. RESULTS: This study demonstrated that DGMI is able to decrease the conduction time of F-VEP and ameliorate histological features induced by optic nerve crush injury in rats. Immunohistochemistry and TUNEL staining results indicated that DGMI can also inhibit cell apoptosis via modulating MAPKs signaling pathways. In addition, treatment with DGMI markedly improved the morphological structures and decreased the apoptotic index in RGC-5 cells. Mechanistically, DGMI could significantly inhibit cell apoptosis by inhibiting p38, JNK and Erk1/2 activation. CONCLUSION: The study shows that DGMI and ginkgolides inhibit RGCs apoptosis by impeding the activation of MAPKs signaling pathways in vivo and in vitro. Therefore, the present study provided scientific evidence for the underlying mechanism of DGMI and ginkgolides on optic nerve crush injury.


Assuntos
Apoptose/efeitos dos fármacos , Lesões por Esmagamento/tratamento farmacológico , Ginkgolídeos/farmacologia , Traumatismos do Nervo Óptico/tratamento farmacológico , Animais , Linhagem Celular , Lesões por Esmagamento/patologia , Modelos Animais de Doenças , Ginkgo biloba/química , Ginkgolídeos/administração & dosagem , Ginkgolídeos/química , Marcação In Situ das Extremidades Cortadas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Meglumina/administração & dosagem , Traumatismos do Nervo Óptico/patologia , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia
2.
Cell Physiol Biochem ; 45(4): 1455-1471, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466787

RESUMO

BACKGROUND/AIMS: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. METHODS: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. RESULTS: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. CONCLUSION: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Isquemia Miocárdica/tratamento farmacológico , Animais , Creatina Quinase Forma MB/sangue , Ciclo-Octanos/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Ginsenosídeos/uso terapêutico , Coração/efeitos dos fármacos , Isoproterenol/toxicidade , L-Lactato Desidrogenase/sangue , Lignanas/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Infarto do Miocárdio/patologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Hormônios Neuro-Hipofisários/toxicidade , Compostos Policíclicos/uso terapêutico , Espirostanos/uso terapêutico , Troponina I/sangue
3.
Neurochem Int ; 103: 45-56, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28049027

RESUMO

Identification and validation of disease-relevant target proteins for natural products is an essential component of modern pharmaceutical research. In the present study, an integrated shotgun proteomics and bioinformatics approach was established to profile the interaction of active small molecules derived from ShengMai preparations (SMXZF) with hundreds of endogenously expressed proteins from middle cerebral artery occlusion (MCAO) model. Affinity-based proteomic strategies for isolation and identification of targets for the bioactive components is a classic, but still powerful approach. The proteins bound by SMXZF of the brain tissue proteins from MCAO model via serial affinity chromatograph were analyzed by nano liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) and all MS/MS spectra were then automatically searched by the SEQUEST program. A total of 154 proteins had been identified, with the molecular weight ranging from 21,369.6 to 332,393.21 and the pI from 4.32 to 10.88. Bioinformatic analysis was also implemented to better understand the identified proteins. In the gene ontology (GO) annotation, all the identified proteins were classified into 39, 18 and 12 groups according to biological process, cellular component and molecular function, respectively. KEGG pathways analysis of the identified proteins was conducted with 46 corresponding pathways found. In addition, the gene network was also constructed to analyze the relationship of these genes each other. Further validation of some targets were performed in MCAO model by Western blotting. The results indeed supported the notion that proteins MAPK/ERK1/2, CaMKII and VIM were involved in the disease development of MCAO and played an essential role in the protective effect of SMXZF. This study highlights the effectiveness and reliability of this integrated shotgun proteomics and bioinformatics approach, which is a promising paradigm for target identification and elucidating the mechanism of natural products in future research.


Assuntos
Encéfalo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteômica , Animais , Encéfalo/metabolismo , Cromatografia Líquida/métodos , Biologia Computacional/métodos , Combinação de Medicamentos , Infarto da Artéria Cerebral Média/metabolismo , Ligantes , Masculino , Camundongos , Anotação de Sequência Molecular/métodos , Proteômica/métodos , Reprodutibilidade dos Testes
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