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1.
J Ethnopharmacol ; 328: 118000, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38527574

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. AIM OF THE STUDY: This study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. MATERIALS AND METHODS: The present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. RESULTS: The results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p-NF-κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p-NF-κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p-NF-κB P65 were downregulated when TLR4 signaling was inhibited. CONCLUSIONS: XNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.


Assuntos
Medicamentos de Ervas Chinesas , Vírus da Influenza A , Influenza Humana , Camundongos , Animais , Humanos , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Pós , Transdução de Sinais
2.
J Hazard Mater ; 468: 133773, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382337

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) in urban fugitive dust, known for their toxicity and ability to generate reactive oxygen species (ROS), are a major public health concern. This study assessed the spatial distribution and health risks of 15 PAHs in construction dust (CD) and road dust (RD) samples collected from June to November 2021 over the cities of Tongchuan (TC), Baoji (BJ), Xianyang (XY), and Xi'an (XA) in the Guanzhong Plain, China. The average concentration of ΣPAHs in RD was 39.5 ± 20.0 µg g-1, approximately twice as much as in CD. Four-ring PAHs from fossil fuels combustion accounted for the highest proportion of ΣPAHs in fugitive dust over all four cities. Health-related indicators including benzo(a)pyrene toxic equivalency factors (BAPTEQ), oxidative potential (OP), and incremental lifetime cancer risk (ILCR) all presented higher risk in RD than those in CD. The multilayer perceptron neural network algorithm quantified that vehicular and industrial emissions contributed 86 % and 61 % to RD and CD BAPTEQ, respectively. For OP, the sources of biomass and coal combustion were the key generator which accounted for 31-54 %. These findings provide scientific evidence for the direct efforts toward decreasing the health risks of fugitive dust in Guanzhong Plain urban agglomeration, China.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Poeira/análise , Monitoramento Ambiental , Medição de Risco , China , Cidades , Redes Neurais de Computação , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise
3.
Front Pharmacol ; 15: 1328632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375037

RESUMO

Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.

4.
J Ethnopharmacol ; 324: 117728, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38216101

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.


Assuntos
Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Animais , Ratos , Espectrometria de Massas em Tandem , Farmacologia em Rede , NF-kappa B , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Receptor Toll-Like 9 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
5.
Oncol Rep ; 51(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38240088

RESUMO

Bone marrow stromal cell antigen 2 (BST2) is a type II transmembrane protein that serves critical roles in antiretroviral defense in the innate immune response. In addition, it has been suggested that BST2 is highly expressed in various types of human cancer and high BST2 expression is related to different clinicopathological parameters in cancer. The molecular mechanism underlying BST2 as a potential tumor biomarker in human solid tumors has been reported on; however, to the best of our knowledge, there has been no review published on the molecular mechanism of BST2 in human solid tumors. The present review focuses on human BST2 expression, structure and functions; the molecular mechanisms of BST2 in breast cancer, hepatocellular carcinoma, gastrointestinal tumor and other solid tumors; the therapeutic potential of BST2; and the possibility of BST2 as a potential marker. BST2 is involved in cell membrane integrity and lipid raft formation, which can activate epidermal growth factor receptor signaling pathways, providing a potential mechanistic link between BST2 and tumorigenesis. Notably, BST2 may be considered a universal tumor biomarker and a potential therapeutical target.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Humanos , Feminino , Antígeno 2 do Estroma da Médula Óssea/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Neoplasias da Mama/patologia , Transdução de Sinais , Biomarcadores Tumorais/genética , Biologia
6.
Virol J ; 20(1): 260, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957630

RESUMO

Influenza A viruses (IAV) are a prevalent respiratory pathogen that can cause seasonal flu and global pandemics, posing a significant global public health threat. Emerging research suggests that IAV infections may disrupt the balance of gut microbiota, while gut dysbiosis can affect disease progression in IAV patients. Therefore, restoring gut microbiota balance may represent a promising therapeutic target for IAV infections. Traditional Chinese medicine, with its ability to regulate gut microbiota, offers significant potential in preventing and treating IAV. This article provides a comprehensive review of the relationship between IAV and gut microbiota, highlighting the impact of gut microbiota on IAV infections. It also explores the mechanisms and role of traditional Chinese medicine in regulating gut microbiota for the prevention and treatment of IAV, presenting novel research avenues for traditional Chinese medicine-based IAV treatments.


Assuntos
Microbioma Gastrointestinal , Vírus da Influenza A , Influenza Humana , Humanos , Medicina Tradicional Chinesa
7.
Toxics ; 11(8)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37624181

RESUMO

Urban fugitive dust is a significant contributor to atmospheric PM2.5 and a potential risk to humans. In 2019, both road dust and construction dust were collected from four cities, including Xi'an, Xianyang, Baoji, and Tongchuan, in Guanzhong Plain, China. Elements, water-soluble ions, and carbonaceous fractions were determined to establish the chemical source profile. High enrichment degrees of Se, Sc, Cl, and Zn in both road dust and construction dust indicated that the industrial system and energy consumption influenced Guanzhong Plain strongly. According to the coefficient of divergence, the two datasets within Xianyang and Tongchuan were similar. Combined with the chemical profile, road dust was affected by more stationary emission sources than construction dust in Xi'an, while biomass burning and vehicle exhaust contributed more to road dust than construction dust in Baoji. Moreover, the health risk of heavy metal was assessed, and corresponding influencing factors were identified. Road dust in all cities showed a non-negligible non-carcinogenic risk for children. Ingestion and inhalation were the main exposure pathways to which As and Co contributed the most, respectively. The land-use regression model revealed that the first-class road in a 100 m radius impacted all high-risk level metals, and the commercial building material and enterprises weakly influenced Co and Pb, respectively.

8.
Biomed Pharmacother ; 157: 114056, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36446240

RESUMO

Ischemic stroke is a common issue that severely affects the human health. Between the central nervous system and the enteric system, the " Gut-Brain " axis, the bidirectional connection involved in the neuro-immuno-endocrine network, is crucial for the occurrence and development of ischemic stroke. Ischemic stroke can lead to change in the gut microbiota and gastrointestinal hormones, which will then reversely affect the disease development. Traditional Chinese Medicine (TCM) has unique advantages with reference to the treatment for ischemic stroke. The latest research revealed that a significant portion of medicines and prescriptions of TCM exert their therapeutic effects by improving the gut microbiota and regulating the secretion of gastrointestinal hormones. The present review summarized the Chinese medicines that play a therapeutic role in cerebral ischemia through regulating the "Gut-Brain" axis and described the corresponding mechanisms. This study attempts to provide reference for clinical selection of Chinese medicines and helps better understand the relevant mechanisms of action.


Assuntos
Hormônios Gastrointestinais , AVC Isquêmico , Humanos , Eixo Encéfalo-Intestino , Medicina Tradicional Chinesa
9.
Front Neurol ; 13: 951536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110390

RESUMO

Ischemic stroke is a highly disabling and potentially fatal disease. After ischemic stroke, autophagy plays a key regulatory role as an intracellular catabolic pathway for misfolded proteins and damaged organelles. Mounting evidence indicates that astrocytes are strongly linked to the occurrence and development of cerebral ischemia. In recent years, great progress has been made in the investigation of astrocyte autophagy during ischemic stroke. This article summarizes the roles and potential mechanisms of astrocyte autophagy in ischemic stroke, briefly expounds on the crosstalk of astrocyte autophagy with pathological mechanisms and its potential protective effect on neurons, and reviews astrocytic autophagy-targeted therapeutic methods for cerebral ischemia. The broader aim of the report is to provide new perspectives and strategies for the treatment of cerebral ischemia and a reference for future research on cerebral ischemia.

10.
Biomed Pharmacother ; 138: 111460, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33711554

RESUMO

Ischaemic stroke (IS) is a common type of stroke characterised by sudden fainting and communication disorders, alongside a number of other symptoms. It is characterised by high morbidity, disability, and mortality rates. Tongqiao Huoxue Decoction (THD) is effective in the treatment of stroke. As a representative prescription for promoting blood circulation and removing blood stasis, THD has been widely used clinically. This paper systematically introduces clinical and experimental studies of THD in the treatment of IS, summarising its clinical application, pharmacological mechanisms, and active components in the treatment of IS. It also explores its key pathways in the treatment of IS through network pharmacology analyses, thereby speculating on its underlying mechanisms. It is of great significance for the secondary development of this classic prescription as well as for the research and development of new drugs.


Assuntos
Pesquisa Biomédica/tendências , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Animais , Isquemia Encefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , AVC Isquêmico/metabolismo , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-33014117

RESUMO

Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) is an important factor in the development of hypertension. Excessive aldosterone can lead to myocardial extracellular matrix collagen proliferation, fibrosis, and cardiomyocyte hypertrophy and aggravate maladaptive remodeling. The results of our previous clinical and animal experiments suggested that Zi Shen Huo Luo Formula (ZSHLF) combined with perindopril can effectively control the process of left ventricular hypertrophy (LVH). The purpose of this study was to investigate whether ZSHLF-treated serum inhibits the membrane localization of the striatin-mediated mineralocorticoid receptor (MR) and affects MR-mediated nongenomic effects and the downstream epidermal growth factor receptor (EGFR)/extracellular regulated kinase (ERK) signaling pathways, thereby improving aldosterone-induced myocardial remodeling. Serum containing ZSHLF was prepared and used to treat rat cardiomyocytes and cardiac fibroblasts in vitro after aldosterone induction and striatin knockdown by small interfering RNA (siRNA). Cell-based assays were carried out to determine the cardiomyocyte surface area and assess the proliferation rate and hydroxyproline secretion of cardiac fibroblasts. Quantitative real-time PCR (qRT-PCR), immunoprecipitation (IP), and Western blotting were performed to evaluate the striatin-mediated MR/EGFR/ERK signaling pathway. In the present study, ZSHLF attenuated the aldosterone-induced hypertrophy of cardiomyocytes and inhibited the proliferation and collagen synthesis of cardiac fibroblasts. ZSHLF also reduced striatin mRNA expression and inhibited striatin and MR binding, membrane MR protein expression, and EGFR and ERK1/2 phosphorylation. Furthermore, after striatin silencing with siRNA, some of the effects of ZSHLF were not changed significantly. In conclusion, ZSHLF inhibits the downstream EGFR/ERK signaling pathway by blocking the striatin-mediated membrane localization of MR, which may be an important molecular mechanism by which ZSHLF improves aldosterone-induced myocardial remodeling.

12.
Front Pharmacol ; 11: 500137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041787

RESUMO

Non-small cell lung cancer (NSCLC), the major form of primary lung cancer, is a common cause of cancer-related death worldwide. Cell adhesion-mediated drug resistance (CAM-DR), a form of chemotherapy resistance, has been reported to confer resistance to various chemotherapeutic agents. Integrin ß1 signaling plays an important role in CAM-DR and has been proposed as a potential target for NSCLC. Wenxia Changfu Formula (WCF) is a Traditional Chinese Compound Prescription for the intervention treatment of NSCLC combined with cisplatin (DDP). This study aims to investigate the effect and mechanism of WCF combined with DDP in reversing CAM-DR. Firstly, the chemical profile of WCF was characterized by UPLC/Q-TOF-MS analysis. A total of 237 compounds with mzCloud Best Match of greater than 70 were identified by using the online database mzCloud. Secondly, we established A549 three-dimensional(3D) cells cultured in vitro and nude mice xenografts models of the A549 cell line with Integrin ß1 overexpression. In vitro, the cell viability, migration and adhesion were measured though MTT Assay, Wound Healing Assay and Cell Adhesion Assay, the Integrin ß1 expression of the A549 cells was assessed through immunocytochemistry; in vitro, the transplanted tumor morphology and the colocalization of Integrin ß1 and its ligands were tested by HE staining and immunofluorescence. As a result, we found that the combination effectively reduced cell viability, suppressed migration and adhesion, and downregulated the protein level of Integrin ß1 in three-dimensional cultured A549 cells. And the combination of WCF with DDP significantly inhibited tumor growth, increased organelle vacuolations and decreased colocalization of Integrin ß1 and its ligands including fibulin-2 and laminin. Taken together, our results confirm that the combination of WCF with DDP could reverse the lung cancer CAM-DR through the Integrin ß1 signaling pathway.

13.
Biomed Pharmacother ; 129: 110380, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32554250

RESUMO

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-ß, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-ß/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-ß/CCL9 pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quimiocinas CC/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/prevenção & controle , Pulmão/efeitos dos fármacos , Proteínas Inflamatórias de Macrófagos/metabolismo , Células Supressoras Mieloides/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Quimiocinas CC/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Proteínas Inflamatórias de Macrófagos/genética , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Carga Tumoral/efeitos dos fármacos
14.
Front Pharmacol ; 11: 383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32317965

RESUMO

Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the efficacy of perindopril in the treatment of hypertensive LVH, but its mechanism is unclear. This study aimed to investigate the possible mechanism to improve the efficacy of perindopril. First, we identified 23 compounds in ZSHLF by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis, among which ferulic acid, caffeic acid, vanillic acid, berberine, rutin, quercetin, kaempferol, stachydrine, and tiliroside have been reported to reduce blood pressure and exhibit cardioprotective effects. Second, we treated spontaneously hypertensive rats (SHRs) with perindopril and ZSHLF for 12 continuous weeks and found that chronic use of perindopril could increase the aldosterone (ALD) levels and cause aldosterone breakthrough (ABT). ZSHLF combined with perindopril reduced the ALD levels, interfered with ABT, decreased blood pressure, improved left ventricular diastolic dysfunction, and decreased the collagen volume fraction; these effects were superior to those of perindopril alone. In vitro experiments, ALD-induced cardiomyocytes (H9c2 cells) and cardiac fibroblasts were treated with ZSHLF-containing serum, which suppressed ALD-induced cardiomyocyte hypertrophy and cardiac fibroblast proliferation, increased mineralocorticoid receptor (MR) and Cav-1 colocalization and decreased phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK) protein expression the cells. In conclusion, ZSHLF can interfere with ABT and affect the pathological role of ALD by affecting MR and Cav-1 interactions and EGFR/ERK signaling pathway. These effects represent a possible mechanism by which ZSHLF improves the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive LVH treatment. However, the major bioactive components or metabolites responsible for the effects and the implications of these findings in patients need further verification.

15.
Genes Brain Behav ; 19(5): e12649, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32129566

RESUMO

According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main signaling pathways underlying the multi-target therapeutic effects of LBRD against depression.


Assuntos
Antidepressivos/farmacologia , Depressão/genética , Extratos Vegetais/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Estresse Psicológico/genética , Transcriptoma , Animais , Antidepressivos/química , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Lilium/química , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Córtex Pré-Frontal/metabolismo , Rehmannia/química , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
16.
J Cancer ; 10(2): 293-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719123

RESUMO

In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin ß1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin ß1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin ß1/PI3K/AKT and apoptosis induction.

17.
Artigo em Inglês | MEDLINE | ID: mdl-28286533

RESUMO

The aim of this study is to investigate the mechanisms of Chinese herbal medicine called "Baoyuan Jiedu" (BYJD for short) decoction, improving life quality and preventing muscle atrophy of cancer cachexia model mice. We showed that the effect of BYJD decoction increased body weights of mice and reduced tumor volume and tumor mass. Furthermore, BYJD decoction increased the gastrocnemii mass and the transverse diameter of muscle fiber morphology. Moreover, BYJD reduced the expression of Atrogin-1 and MuRF-1 protein. Collectively, our results show that BYJD decoction improves the life quality of cancer cachexia mice and prevents muscle atrophy by downregulating expression of Atrogin-1 and MuRF-1.

18.
Chin J Integr Med ; 22(10): 752-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26666762

RESUMO

OBJECTIVE: To explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo. METHODS: Thirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively. RESULTS: Compared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05). CONCLUSION: WCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Apoptose , Resistencia a Medicamentos Antineoplásicos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Feminino , Imunofluorescência , Humanos , Marcação In Situ das Extremidades Cortadas , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carga Tumoral/efeitos dos fármacos , Receptor fas/metabolismo
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(12): 3282-5, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24611387

RESUMO

Rock spectrum research is the base of the remote sensing geology. It's of great significance of exploring the relations between rock spectrum and other rock natures. In the present study, 36 fine crushed lava samples each measuring 5 cmX5 cmX 5 cm were tested for its spectrums by SVC HR-768 portable spectrometer. But before measuring each sample, white boards should be calibrated and after measuring the curves of spectrum of each sample should make a 5 nm smooth resample so that meteoric water and noise caused by external environment can be eliminated. After such smooth resample, at the spectrum scope of 1 112-1322 nm, taking band value as horizontal axis and reflectivity as vertical axis, linear equations of rock samples can be obtained. Taking the slopes as the horizontal axis and volume magnetic susceptibility as vertical axis, y= -0. 256 31n(x) + 0. 913 7 was thus obtained and its equation correlation coefficient is up to 0. 78. The result shows that volume magnetic susceptibility is mainly caused by Fe2+ , and that the amount of Fe2+ can be almost measured in the spectrum scope of 1112 approximately 1322 nm that has a good correlation with volume magnetic susceptibility.

20.
Oncol Rep ; 28(1): 147-54, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22552406

RESUMO

Lung adenocarcinoma, with increased incidence in the world, exhibits poor prognosis and is usually resistant to conventional chemotherapy due to drug resistance. The enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in tumorigenesis and cancer development through chromatin remodeling in various types of cancer. However, its potential role in lung adenocarcinoma has not been well defined. In this study, the expression of EZH2 was examined in lung adenocarcinoma tissues and cell lines. Most interestingly, EZH2 overexpression was detected in tumor tissue and significantly correlated with histological differentiation, pathological tumor-node-metastasis stage and smoking history, but not with gender or age. Furthermore, EZH2 overexpression was also detected in cisplatin-resistant cancer cells rather than cisplatin-sensitive cells. Short hairpin RNA targeted against EZH2 inhibited cell proliferation and migration, and led to G(2)/M cell cycle arrest and apoptosis in both cisplatin-resistant and cisplatin-sensitive cell lines. Moreover, EZH2 knockdown enhanced cisplatin sensitivity of cisplatin-resistant cells and reduced the expression levels of multidrug resistance-related protein 1. Our study suggests that EZH2 contributes to the progression of lung adenocarcinoma, and the deletion of EZH2 inhibits cancer and resensitizes cells to cisplatin in lung adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma de Pulmão , Adulto , Idoso , Antineoplásicos/farmacologia , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Cisplatino/farmacologia , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Complexo Repressor Polycomb 2 , Interferência de RNA , Fatores de Transcrição/genética
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