RESUMO
Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.
Assuntos
Apiaceae , Cumarínicos , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Apiaceae/química , Cumarínicos/química , Cumarínicos/farmacologia , Cumarínicos/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Raízes de Plantas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Relação Estrutura-Atividade , Nitrilas/químicaRESUMO
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characteristized by the presence of dyskinesia and the progressive loss of dopaminergic neurons. Although certain drugs can mitigate the symptoms of PD, they are unable to delay the disease progression, and their prolonged use may result in complications. Therefore, there exists an urgent necessity to identify potential agents that can effectively delay PD progression with fewer side effects. Recent research has unveiled that several traditional Chinese medicines (TCM) exhibit neuroprotective properties in various models pertinent to PD. Forsythoside A (FSA), the primary bioactive compound derived from TCM Lianqiao, has undergone extensive research in animal models of Alzheimer's disease and cerebral ischemia. However, the investigation into the impact of FSA on PD is limited in existing research. In this study, we aimed to evaluate the neuroprotective effects of FSA on MPTP-induced PD mouse model. FSA demonstrated significant improvements in the behavioral and neuropathological changes triggered by MPTP in mice. Furthermore, it exerted a suppressive effect on the activations of astrocyte and microglia. Meanwhile, Tandem mass tag (TMT)-based quantitative proteomics of striatal tissue and bioinformatics analysis were performed to elucidate the underlying mechanisms of FSA on PD mouse model. Proteomics demonstrated a total of 68 differentially expressed proteins (DEPs) were identified between HFSA and MPTP groups including 26 upregulated and 42 downregulated. Systematic bioinformatics analysis of the 68 DEPs illustrated that they were predominantly related to estrogen signaling pathway and calcium signaling pathway. The related DEPs (PLCß4, Grm2, HPAC and Cox4i1) expression levels were verified by Western blot. FSA effectively restored the altered expression of the four DEPs induced by MPTP. Summarily, FSA exerted remarkable neuroprotective effects in MPTP-induced mice. Further, our research may provide proteomics insights that contribute to the further exploration of FSA as a potential treatment for PD.
Assuntos
Medicamentos de Ervas Chinesas , Forsythia , Glicosídeos , Intoxicação por MPTP , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Camundongos , Doença de Parkinson/metabolismo , Intoxicação por MPTP/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Proteômica , Neurônios Dopaminérgicos/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologiaRESUMO
Traditional Chinese medicine (TCM) is a promising strategy for effectively treating cancer by inducing cellular senescence with minimal side effects. Si-Wu-Tang (SWT) is a TCM composed of four herbs that is commonly used in China for the treatment of gynecological diseases; SWT can prevent breast cancer (BC), but the molecular mechanism by which SWT induces cellular senescence and its clinical application value remain unknown. We identified 335 differentially expressed genes (DEGs) in SWT-treated MCF-7 cells through Gene Expression Omnibus (GEO) dataset analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the enrichment of biological processes and key signaling pathways including cellular senescence, the cell cycle, the MAPK signaling pathway, and the p53 signaling pathway. Additionally, SWT induced BC cell senescence by upregulating the expression of 33 aging/senescence-induced genes (ASIGs). According to LASSO regression analysis, NDRG1, ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 levels were associated with BC prognosis and were used to develop risk scores. ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 were identified as protective factors (P < 0.05, HR < 1), while NDRG1 was identified as a risk factor (P < 0.05, HR > 1). Notably, patients with low risk scores had increased senescence-associated secretory phenotypes (SASPs) and immune cell infiltration. Overall, we systematically integrated biological databases and biocomputational methods to reveal the mechanisms by which SWT induces senescence in breast cancer and its clinical value.
Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Senescência Celular , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Células MCF-7 , Medicina Tradicional ChinesaRESUMO
Traditional Chinese medicine (TCM) is a promising and effective treatment for cancer with minimal side effects through a multi-active ingredient multitarget network. Radix Bupleuri and Rhizoma Cyperi are listed as herbs dispersing stagnated liver Qi in China. They have been used clinically to treat liver diseases for many years and recent pharmacological studies have shown that they inhibit the proliferation of hepatocellular carcinoma (HCC). However, the pharmacological mechanisms, potential targets, and clinical value of the Radix Bupleuri-Rhizoma Cyperi herb pair (CXP) for suppressing HCC growth have not been fully elucidated. We identified 44 CXP targets involved in the treatment of HCC using the GEO dataset and HERB database. An analysis of the Traditional Chinese Medicine System Pharmacology Database (TCMSP) showed that CXP exerts synergistic effects through 4 active ingredients, including quercetin, stigmasterol, isorhamnetin, and kaempferol. GO and KEGG analyses revealed that CXP mainly regulates HCC progression through metabolic pathways, the p53 signaling pathway, and the cell cycle. Additionally, we applied The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) database to perform the expression patterns, clinical features, and prognosis of 6 genes (CCNB1, CDK1, CDK4, MYC, CDKN2A, and CHEK1) in cell cycle pathways to reveal that CXP suppresses HCC clinical therapeutic value. Moreover, based on molecular docking, we further verified that CXP exerts its anti-HCC activity through the interaction of multiple active components with cell cycle-related genes. We systematically revealed the potential pharmacological mechanisms and targets of CXP in HCC using multilevel data integration and molecular docking strategies.
Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Medicina Tradicional ChinesaRESUMO
OBJECTIVE: To observe the clinical therapeutic effect of the combination of electroacupuncture (EA) at Baliao points (bilateral Shangliao [BL 31], Ciliao [BL 32], Zhongliao [BL 33] and Xialiao [BL 34]) and oral administration of mifepristone tablets and its influence on uterine volume restoration after uterine curettage of incomplete abortion as compared with simple oral administration of mifeprstone tablets. METHODS: A total of 58 patients after uterine curettage of incomplete abortion were randomized into an EA group and a western medication group, 29 cases in each one. In the western medication group, mifepristone tablets were administered orally, 2 tablets each time, once daily. In the EA group, on the base of the treatment as the western medication group, EA was applied to Baliao points, with disperse-dense wave, once daily, 50 min each time. The treatment for 3 days was as one course and 2 courses of treatment were required, at the interval of 1 day in the two courses. Before and after treatment, the area of intrauterine residue and blood flow signal positive rate of color Doppler flow imaging (CDFI) were recorded in patients of the two groups respectively. The days of vaginal bleeding and the rate of second operation were recorded after treatment in patients of the two groups. Using the three-dimensional ultrasound B reconstruction, the uterine endometrial volume after menstruation resumption was measured in patients of the two groups, and the clinical therapeutic effect was evaluated. RESULTS: After treatment, the intrauterine residue area and CDFI blood flow signal positive rate were all reduced as compared with the values before treatment in patients of the two groups (P<0.05). After treatment, the intrauterine residue area and CDFI blood flow signal positive rate in the EA group were less than those in the western medication group (P<0.05). After treatment, the days of vaginal bleeding in patients of the EA group were less than that in the western medication group and the rate of second operation was lower than the western medication group (P<0.05). The uterine endomentrial volume after menstruation resumption in the EA group was larger than that in the western medication group after treatment (P<0.05). The total effective rate was 55.2% (16/29) in the EA group, higher than 37.9% (11/29) in the western medication group (P<0.05). CONCLUSION: The combined treatment of electroacupuncture at Baliao points and oral administration of mifepristone tablets effectively promotes uterine contraction, softens and discharges intrauterine residue and contributes to uterine volume restoration in the patients after uterine curettage of incomplete abortion. The therapeutic effect of this combined therapy is better than simple oral administration of mifepristone tablets.
Assuntos
Aborto Incompleto , Aborto Induzido , Eletroacupuntura , Aborto Incompleto/terapia , Pontos de Acupuntura , Curetagem , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Post-stroke depression (PSD) is the most common emotional problem after stroke. It can lower the quality of life and increase the recurrence and mortality. Pharmacological agents have been shown to treat PSD. However, the benefits of pharmacotherapy are debatable and the side-effects are significant. More and more clinical trials suggest that acupuncture plays an important role in patients with PSD. The primary purposes of the study are to conduct a Bayesian analysis of randomized trials to determine the effect of acupuncture and investigate the effect of several acupuncture therapies on PSD. METHODS: We will retrieve articles from 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, and WHO International Clinical Trials Registry (TCTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. The publication period will be from inception to January 2019. All randomized controlled trials that evaluate the safety and efficacy of acupuncture on PSD will be included. The primary outcomes will be the change in the degree of depression as measured by the Hamilton Depression Scale and Beck Depression Inventory. Two reviewers will separately extract the data and assess the risk of bias by using the Cochrane Collaboration's risk of bias tool. Bayesian analysis will be conducted to pool the effects of several acupunctures. The ranking probabilities for several acupunctures (simple acupuncture, fire needle, warm acupuncture, auriculo-acupuncture, or electroacupuncture) will be estimated by the surface under the cumulative ranking curve. RESULT: This study will provide reliable evidence for acupuncture on PSD. CONCLUSION: The results of this review will introduce a safe and effective treatment and provide reliable evidence to evaluate the effectiveness of several acupuncture therapies on PSD. TRIAL REGISTRATION NUMBER: CRD42019132725.
Assuntos
Terapia por Acupuntura/métodos , Teorema de Bayes , Depressão/etiologia , Depressão/terapia , Acidente Vascular Cerebral/complicações , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de PesquisaRESUMO
RATIONALE: Moxibustion, an important therapeutic measure of TCM, can stimulate acupoints to unblock the meridians and collaterals, regulate the function of qi and blood, support health, and expel pathogens. So it could be an effective and safe for the treatment of constipation and improvement of the quality of life in poststroke patients with constipation. PATIENT CONCERNS: He has a history of constipation, with the defecation of hard, bound stool every 2 to 3 days with the help of glycerin enema. DIAGNOSES: Constipation for >6 months; Cerebral infarction for 9 months; Type 2 diabetes for 3 years. Hypertension for approximately 1 month. INTERVENTIONS: From the fifth day after admission, 5 rounds of moxibustion with moxa cones were administered at the bilateral ST25 and CV6 acupoints. OUTCOMES: The patient successfully defecated within 1hour. Subsequently, the patient could maintain daily unobstructed defecation with a normal total stool weight and moderate hardness. LESSONS: Moxibustion is effective and safe for the treatment of constipation and improvement of the quality of life in post-stroke patients with constipation.