RESUMO
BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors with the highest mortality in the world. Modern pharmacological studies have shown that Syringin has an inhibitory effect on many tumors, but its anti-BC efficacy and mechanism are still unclear. METHODS: First, Syringin was isolated from Acanthopanax senticosus (Rupr. & Maxim.) Harms (ASH) by systematic solvent extraction and silica gel chromatography column. The plant name is composed of genus epithet, species additive words and the persons' name who give its name. Then, the hub targets of Syringin against BC were revealed by bioinformatics. To provide a more experimental basis for later research, the hub genes which could be candidate biomarkers of BC and a ceRNA network related to them were obtained. And the potential mechanism of Syringin against BC was proved in vitro experiments. RESULTS: Syringin was obtained by liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC). Bioinformatics results showed that MAP2K1, PIK3CA, HRAS, EGFR, Caspase3, and PTGS2 were the hub targets of Syringin against BC. And PIK3CA and HRAS were related to the survival and prognosis of BC patients, the PIK3CA-hsa-mir-139-5p-LINC01278 and PIK3CA-hsa-mir-375 pathways might be closely related to the mechanism of Syringin against BC. In vitro experiments confirmed that Syringin inhibited the proliferation and migration and promoted apoptosis of BC cells through the above hub targets. CONCLUSIONS: Syringin against BC via PI3K-AKT-PTGS2 and EGFR-RAS-RAF-MEK-ERK pathways, and PIK3CA and HRAS are hub genes for adjuvant treatment of BC.
Assuntos
Neoplasias da Mama , Glucosídeos , MicroRNAs , Fenilpropionatos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Ciclo-Oxigenase 2/metabolismo , Receptores ErbB/metabolismo , Feminino , Glucosídeos/farmacologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fenilpropionatos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases raf/metabolismo , Proteínas ras/metabolismoRESUMO
It remains a technical challenge to accurately identify close species of herbal medicines, especially from adulterants, because of their highly identical phenotypes and chemical compositions. Here, we report a direct, sequencing-free, high-curvature nanostructuring-based electrochemical herb sensor (nanoE-herb sensor) to identify herbal species quickly and accurately using ITS2 barcodes. We engineer a nano-roughened carbon-supported gold nanostructuring array by photolithograph-free, one-step electrodeposition. The 3D fractal nanostructures exhibit a high deflection angle that largely enhances DNA hybridization efficiency, particularly for the midcomplementary hybridization, as compared to the 2D planar surface. More importantly, such a trans-scale array biointerface (including macroscale carbon and nanoscale gold branches) can overcome the detection barrier of slow diffusion of a long genomic sequence and inaccessibility of the sequestered variations in ITS2 secondary structures through the out-protruded 3D functional nanostructures. Our nanoE-herb sensor achieves a detection limit of 0.18 fM for the 64-mer fragment of saffron ITS2 barcode with midhybridization and shows superior specificity against even single-base mismatch. The sensor also precisely differentiates saffron from six other adulterants by directly detecting unpurified asymmetric PCR amplicons (â¼500 bp) with ITS2 sequences, suggesting its great potential in the field identification of herbal medicinal species and pathogenic bacteria with specific DNA barcodes.
Assuntos
Código de Barras de DNA Taxonômico , DNA de Plantas/genética , Medicamentos de Ervas Chinesas/análise , Nanoestruturas/química , Técnicas Eletroquímicas , Hibridização de Ácido Nucleico , Plantas Medicinais/genéticaRESUMO
Rubia cordifolia L. is widely used in Asia and its antihepatoma effect has been proved by in vitro and in vivo experiments. However, there are few studies on its specific mechanism. In the present study, the network pharmacology method was used to construct the component/target/pathway molecular regulatory network for the antihepatoma effect of Rubia cordifolia L. to explore the effective components of Rubia cordifolia L. and its potential mechanism. The chemical components of Rubia cordifolia L. were identified through literature and databases, and the components were evaluated and screened by drug likeness and pharmacokinetic characteristics (ADMET). The targets of active components were predicted according to the reverse pharmacophore matching model. The hepatic carcinoma-related genes were found in databases, and antihepatoma-related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the Database for Annotation, Visualization and Integrated Discovery, and the component/target/pathways network of antihepatoma effect of Rubia cordifolia L. was constructed using Cytoscape software. Finally, 16 active compounds were screened from Rubia cordifolia L., and 39 gene targets, including AKT1, mitogen-activated protein kinase 1, and epidermal growth factor receptor, were involved. Rubia cordifolia L. also affected the hepatitis B, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase signaling pathways. Many direct-acting tumor-related signaling pathways and indirect-acting hepatitis pathways inhibit the generation of liver cancer. The present study provided a scientific basis for further elucidating the mechanism of Rubia cordifolia L. against liver cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rubia/química , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologiaRESUMO
Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.
Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Matriz Extracelular/metabolismo , Extratos Vegetais/farmacologia , Plectranthus/química , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Asma/metabolismo , Tosse/metabolismo , Citocinas/metabolismo , Cobaias , Inflamação/tratamento farmacológico , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that chinensinaphthol methyl ether and neojusticin B may target the integrin αIIbß3 protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin αIIbß3 protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that chinensinaphthol methyl ether and neojusticin B target the integrin αIIbß3 protein.
Assuntos
Acanthaceae/química , Derivados de Benzeno/farmacologia , Dioxolanos/farmacologia , Éteres/farmacologia , Lignanas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Derivados de Benzeno/química , Derivados de Benzeno/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Relação Dose-Resposta a Droga , Éteres/química , Éteres/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Testes de Função Plaquetária , Relação Estrutura-AtividadeRESUMO
Systemic lupus erythematosus (SLE) is a serious disorder of immune regulation characterized by overproduction of autoantibodies, lupus nephritis, CD4+ T cell aberrant activation, and immune complex-mediated inflammation. The chronic graft vs. host disease (cGVHD) mouse model is a well-established model of SLE. Quercitrin is a natural compound found in Tartary buckwheat with a potential anti-inflammatory effect that is used to treat heart and vascular conditions. In our previous study, we determined that quercitrin is an immunosuppressant with beneficial effects in mouse models of immune diseases. We hypothesized that quercitrin could prevent lupus nephritis in the cGVHD mouse model by decreasing the production of autoantibodies and inflammatory cytokines, and reducing immune cell activation. cGVHD was induced by injecting DBA/2 spleen cells into the tail vein of BDF1 mice. The cGVHD mice exhibited significant proteinuria, which is a marker of nephritis. Quercitrin decreased the number of serum antibodies, CD4+ T cell activation, as well as the expression levels of T-bet, GATA-3, and selected cytokines. Moreover, quercitrin treatment decreased the expression of inflammatory genes and cytokines in the kidney, as well as in peritoneal macrophages. In addition, quercitrin inhibited LPS-induced cytokines as well as the phosphorylation of ERK, p38 MAPK, and JNK in Raw264.7 cells. Overall, quercitrin ameliorated the symptoms of lupus nephritis in the cGVHD mouse model, which may be due to the inhibition of CD4 T cell activation and anti-inflammatory effects on macrophages.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Quercetina/análogos & derivados , Animais , Autoanticorpos/biossíntese , Linfócitos T CD4-Positivos/efeitos dos fármacos , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/biossíntese , Fator de Transcrição GATA3/genética , Lipopolissacarídeos/antagonistas & inibidores , Ativação Linfocitária/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos DBA , Proteinúria/etiologia , Quercetina/uso terapêutico , Células RAW 264.7 , Baço/citologia , Baço/transplanteRESUMO
At the urgent request of Coptis chinensis planting,growth suitability as assessment indicators for C. chinensis cultivation was proposed and analyzed in this paper , based on chemical quality determination and ecological fators analysis by Maxent and ArcGIS model. Its potential distribution areas at differernt suitability grade and regionalization map were formulated based on statistical theory and growth suitability theory. The results showed that the most suitable habitats is some parts of Chongqing and Hubei province, such as Shizhu, Lichuan, Wulong, Wuxi, Enshi. There are seven ecological factor is the main ecological factors affect the growth of Coptidis Rhizoma, including altitude, precipitation in February and September and the rise of precipitation and altitude is conducive to the accumulation of total alkaloid content in C. chinensis. Therefore, The results of the study not only illustrates the most suitable for the surroundings of Coptidis Rhizoma, also helpful to further research and practice of cultivation regionalization, wild resource monitoring and large-scale cultivation of traditional Chinese medicine plants.
Assuntos
Coptis/crescimento & desenvolvimento , Alcaloides/análise , China , Coptis/química , Ecologia , Ecossistema , Sistemas de Informação Geográfica , Rizoma/química , Rizoma/crescimento & desenvolvimentoRESUMO
Ten flavonoids were isolated from the 95% ethanol extract of the seeds of Alpinia galanga Willd. with a combination of various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. On the basis of spectroscopic data analysis, they were elucidated as (2R, 3S)-pinobaksin-3-cinnamate (1), (2R, 3R)-pinobaksin-3-cinnamate (2), pinocembrin (3), pinobaksin (4), 3-O-acetylpinobaksin (5), galangin (6), galangin-3-methylether (7), kumatakenin (8), 3-methylkaempferol (9) and (2R, 3R)-3, 5-dihydroxy-7-methoxyflavanone (10). Among them, compound 1 is a new compound, compounds 2, 5 and 10 were isolated from the genus Alpinia for the first time, and others were isolated from this plant for the first time.
Assuntos
Alpinia/química , Cinamatos/isolamento & purificação , Plantas Medicinais/química , Benzopiranos/química , Benzopiranos/isolamento & purificação , Cinamatos/química , Flavanonas/química , Flavanonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Quempferóis/química , Quempferóis/isolamento & purificação , Estrutura Molecular , Sementes/químicaRESUMO
To study ecology suitability rank dividing of the total alkaloid content of Coptis Rhizoma for selecting artificial planting base and high-quality industrial raw material in Chongqing province. Based on the investigation of PCB and DEM data of Chongqing province, the relationship between the total alkaloid content in Coptis Rhizoma and topographical conditions was analyzed by statistical analysis. The geographic information systems (GIS)-based assessment and landscape ecological principles were applied to assess eco logy suitability areas of Coptis Rhizoma in Chongqing. slope, aspect and altitude are main topographical factors that affect the content of the total alkaloid content in Coptis Rhizoma The total alkaloid content in Coptis Rhizoma is higher in the lower altitude, shady slope and bigger slope areas. The total alkaloid content is higher in the south areas of Chongqing province and lower in the northeast. Terrain conditions of the southern region of Chongqing are most suitable for The accumulated of total alkaloid Coptis Rhizoma content.
Assuntos
Alcaloides/análise , Coptis/química , Rizoma/química , Alcaloides/metabolismo , China , Ecologia , Meio Ambiente , Sistemas de Informação Geográfica , Geografia , Plantas MedicinaisRESUMO
The existing processing methods, commercial specification and grades, and the marketing of Coptidis Rhizoma were systematical researched, referring to ancient, modern and contemporary medical literatures with the combination of our fieldwork on main origins of Coptidis Rhizoma and some herbs markets. Results showed that Coptidis Rhizoma processing methods mainly included sun-dried method and baked method anciently. For now, the processing methods become various, including thin paper-covering under the sun drying, direct drying, oven drying and microflame-fry drying. In the literatures, the main chemical constituent berberine was determined of its content to analyze the processing methods, finding that the sun drying and baked drying affect the berberine content, so the temperature must be controlled when drying. The thin paper-covering drying method is so cumbersome for large quantities of medicinal herbs and in wind conditions that it has been eliminated. Eventually, direct drying, oven drying and microflame-fry drying are chosen to the large-scale socialized production for their convenient and simple operation, making up the current main processing methods. Coptidis Rhizoma products have 3 specifications of Weilian, Yalian, Yunlian, of each specification there are 2 levels, but in fact the market of Weilian commodities overtakes the Yunlian, which only sold in parts of Yunnan, and the no-sale Yalian. The mainstream commercial Weilian are often sold in general way, gradeless and uniformly-priced. There are regional differences of the processing methods on Coptidis Rhizoma, which needs unified research and development of relevant standard operating procedures to ensure the quality of medicine, urgently. Coptidis Rhizoma product specifications and the intrinsic quality-grade correlation need to be further improved, which could provide a more reliable standard for quality at competitive prices, and it is recommended that "medicinal commercial specification and grade standard" content be increased into the Herbs part of Chinese Pharmacopoeia.
Assuntos
Química Farmacêutica/métodos , Coptis/química , Medicamentos de Ervas Chinesas/química , Rizoma/química , China , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
BACKGROUND: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). PURPOSE: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. METHODS: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. RESULTS: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1ß in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.
Assuntos
Lesão Pulmonar Aguda , Anti-Inflamatórios , Cinnamomum aromaticum , Macrófagos , Óleos Voláteis , Casca de Planta , Animais , Masculino , Camundongos , Acroleína/análogos & derivados , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Anti-Inflamatórios/farmacologia , Cinnamomum aromaticum/química , Modelos Animais de Doenças , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Casca de Planta/química , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.
Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Fator 2 Relacionado a NF-E2 , Óxido Nítrico Sintase Tipo III , Animais , Ratos , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/metabolismo , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , AVC Isquêmico/prevenção & controle , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Hugan Buzure Granule (HBG) is a traditional prescription of Uygur nationality in China mainly used to treat liver cold, stomachache, spleen and rib pain, arthralgia, rheumatism and urinary system diseases. Its mechanism of action in treating acute kidney injury (AKI) continues to remain unconfirmed. This study's objective was to investigate the pharmacodynamics and mechanism of HBG in the management of AKI. METHODS: The damage to the kidney tissue was examined by using H&E (Hematoxylin-eosin) staining. The BUN (Blood Urea Nitrogen) and Cr (Creatinine) in serum were examined by biochemical kit. The content of ROS (Reactive oxygen species) in kidney tissue was determined by ROS frozen section staining, while the amount of MDA (Malondialdehyde), GSH (Glutathione), and the enzymes of CAT (Catalase) and SOD (Superoxide dismutase) were assessed by using a biochemical kit. The tissue apoptosis was seen by using the TUNEL assay. ELISA kit was utilized to assess the content of IL-6, TNF-α, and IL-1ß in serum. Immunohistochemistry and Western blot were utilized to identify the translation of proteins associated to the NLRP3/Caspase-1 pathway and the TLR4/NF-κB pathway in various tissues. RESULTS: HBG considerably improved the renal injury in mice and decreased their kidney coefficient in contrast with the Control group. Immunohistochemistry and Western blot demonstrated that the translation of NLRP3, Caspase-1, IL-18, IL-1ß, TLR4, NF-κB, IL-6, TNF-α were down-regulated in HBG groups. CONCLUSIONS: HBG may have a protective effect against AKI through anti-oxidative stress, inhibition of apoptosis and reduction of serum inflammatory factor levels. The mechanisms involved inhibiting NLRP3/Caspase-1 pathway and TLR4/NF-κB pathway.
Assuntos
Injúria Renal Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Caspase 1/metabolismo , Fator de Necrose Tumoral alfa , Transdução de Sinais , Interleucina-6 , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismoRESUMO
BACKGROUND: Benign and malignant liver tumors are prevalent worldwide. However, there is no effective and comprehensive treatment option for many patients with malignant tumors. Thus, it is critical to prevent benign tumors from worsening, increasing the number of treatment options and effective medications against malignant liver tumors. Oleuropein is a natural and non-toxic product and inhibits tumor growth in various ways. METHODS: We employed bioinformatics analysis and molecular docking to identify potential targets of oleuropein. Surface plasmon resonance (SPR) was used to determine the direct binding strength of the target and compounds. Essential functionalities of the targets were analyzed using gene interference approaches. Transcriptomic studies were performed to observe the global genomic alterations occurring inside cells. Changes in glycolytic metabolites and gene and protein expressions were also detected. The anti-tumor benefits of oleuropein in vivo were determined using a tumor-bearing mouse model. RESULTS: Glucose-6-phosphate isomerase (GPI) was found to be a direct target of oleuropein. GPI discontinuation in liver tumor cells altered the expression of many genes, causing glycogenolysis. GPI interference was associated with PYGM and PFKFB4 inhibitors to inhibit glycolysis in liver tumors. Oleuropein inhibited glycolysis and showed good anti-tumor activity in vivo without adverse side effects. CONCLUSIONS: GPI is a crucial enzyme in glycolysis and the immediate target of oleuropein. GPI expression inside tumor cells affects different physiological functions and signal transduction. Oleuropein has depicted anti-tumor action in vivo without harmful side effects. Moreover, it can control tumor glycolysis through GPI.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Simulação de Acoplamento Molecular , Glucosídeos Iridoides , Glicólise , Iridoides/farmacologiaRESUMO
In this review, the authors summarized the new technologies and methods for identifying traditional Chinese medicinal materials, including molecular identification, chemical identification, morphological identification, microscopic identification and identification based on biological effects. The authors introduced the principle, characteristics, application and prospect on each new technology or method and compared their advantages and disadvantages. In general, new methods make the result more objective and accurate. DNA barcoding technique and spectroscopy identification have their owner obvious strongpoint in universality and digitalization. In the near future, the two techniques are promising to be the main trend for identifying traditional Chinese medicinal materials. The identification techniques based on microscopy, liquid chromatography, PCR, biological effects and DNA chip will be indispensable supplements. However, the bionic identification technology is just placed in the developing stage at present.
Assuntos
Medicamentos de Ervas Chinesas/química , Código de Barras de DNA Taxonômico , Medicina Tradicional Chinesa , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da PolimeraseRESUMO
Objective: To predict the mechanism of Shengmai Injection (SMI) in the acute treatment of COVID-19 by network pharmacology and molecular docking. Methods: Search the compounds in the Traditional Chinese Medicine Systems Pharmacology (TCMSP), and screen them by Drug-like properties (DL) and Oral bioavailability (OB); Using PharmMapper database and GeneCards database to collect compounds targets and COVID-19 targets, and using UniProt database to standardize the names of target genes; Using DAVID database for KEGG pathway annotation and GO bioinformatics analysis; Using Cytoscape 3.8.2 software and STRING 10.5 database to construct "Component-Target-Pathway" network and Protein-Protein Interaction network (PPI); Using molecular docking to predict the binding ability of key compounds and key proteins. Results: A total of 34 active components, 38 core targets and 180 signaling pathways were screened out. The results of molecular docking showed that Schisantherin A and Moupinamide have strong binding with EGFR and MAPK1. Conclusion: The key active compounds of SMI in the treatment of COVID-19 may be Schisantherin A and Moupinamide, and the molecular mechanism may be related to key targets such as EGFR and MAPK1, and may be involved in the PI3K-Akt signaling pathway and MAPK signaling pathway.
RESUMO
Mollugin has been proven to have anti-tumor activity. However, its potential anti-tumor mechanism remains to be fully elaborated. Herein, we investigated the growth inhibition of HepG2 cells, as well as the anti-tumor effect of mollugin and its molecular mechanism on H22-tumor bearing mice. In vitro, mollugin was shown to have a strong inhibitory effect on HepG2 cells in a concentration-dependent manner. Mollugin induced S-phase arrest of HepG2 cells, and increased intracellular reactive oxygen species (ROS) levels. Comet assay demonstrated that mollugin induced DNA damage in HepG2 cells, as well as an increase in the expression of p-H2AX. In addition, mollugin induced changes in cyclin A2 and CDK2. However, the addition of antioxidant glutathione (GSH) was able to reverse the effect of mollugin. In vivo, mollugin significantly inhibited tumor growth and reduced the tendency of tumor volume growth in mice. The tumor cell density was found to be decreased in the administration group, and the content of ROS in the tumor tissue significantly increased. The expression of p-H2AX, cyclin A2 and CDK2 were consistent with in vitro results. Mollugin demonstrated anti-hepatocellular carcinoma activity in vitro and in vivo, and its anti-hepatocellular carcinoma activity was found to be related to DNA damage and cell cycle arrest induced by excessive ROS production in cells.
Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Piranos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Antioxidantes/química , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Ciclina A2/genética , Ciclina A2/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Dano ao DNA/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Piranos/química , Piranos/uso terapêuticoRESUMO
[This corrects the article DOI: 10.7150/ijbs.57164.].
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. is a traditional Chinese medicine, first recorded in "Shen Nong's Herbal Classic", for the treatment of lumbar pain and fever. As a widely distributed herb, it has also been documented in India, Nepal, and Malaysia. In "Tang Materia Medica", a famous medicinal book of Tang Dynasty in ancient China, it was first used to treat diseases associated with blood stasis. Blood stasis syndrome is closely related to thrombus formation and platelet aggregation. Although some compounds isolated from this plant have anti-platelet aggregation effects, the main chemical components and mechanism of J. procumbens in terms of these effects are little known. AIMS OF THE STUDY: Through in vivo and in vitro experiments, this studsy revealed the characteristic components and action mechanism of anti-platelet aggregation by J. procumbens from an overall perspective. MATERIALS AND METHODS: The effective crude extracts of the whole plant were screened via an in vitro anti-platelet aggregation test. After incubating these extracts with apheresis platelets, high affinity compounds were detected by HPLC-MS and regulatory genes were detected using gene chips. The effective components and potential target proteins were analyzed using computational docking technology. Furthermore, the compound with the strongest predicted activity was evaluated in vivo via an anti-thrombotic test. RESULTS: Integrin aâ ¡bß3, PKCα, PI3Kγ, and mitogen-activated protein kinase 14 were found to be potential targets. Justicidin B, tuberculatin, chinensinaphthol methyl ether, and neojusticin B were effective compounds that inhibited human platelet aggregation by suppressing Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways. Among the compounds that bind to platelets, justicidin B showed the strongest virtual binding force. The test of carotid artery thrombosis induced by ferric chloride in SD rats confirmed that justicidin B inhibited thrombus formation. CONCLUSION: Experimental investigation showed that arylnaphthalene lignan aglycones with one methylenedioxy group and two methoxy groups are effective components for anti-platelet aggregation by J. procumbens. These compounds inhibit Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways by suppressing the expression of genes such as ITGB3, PRKCA, PIK3CG, and MAPK14. These results reflected the characteristics of multi-component and multi-target synergistic treatment of Chinese medicine.
Assuntos
Justicia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Justicia/química , Fosfatidilinositol 3-Quinases , Agregação Plaquetária , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
We have shown previously that glycyrol has an inhibitory effect on the immune response in mice by reducing calcineurin activity (Li et al., 2010, Pharm Biol 48:11771184). Here, we investigated the interaction of glycyrol with calcineurin A (CNA, catalytic A subunit of calcineurin) by spectroscopic methods and docking. We showed that glycyrol binds to CNA via hydrophobic interactions in a ratio of 1:1, and the main binding site is in the catalytic domain of CNA close to the calcineurin B subunit-binding domain. Binding of glycyrol changes the secondary structure of CNA, and this effect may possibly inhibit CN activity.