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ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.
Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos C57BL , Mitofagia , Miócitos Cardíacos , Resposta a Proteínas não Dobradas , Animais , Mitofagia/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Camundongos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/ultraestrutura , Comprimidos , Linhagem Celular , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.
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Doença das Coronárias , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Humanos , Medicina Tradicional Chinesa , Deficiência da Energia Yang , Deficiência da Energia Yin , Estudos Transversais , Estudos Retrospectivos , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Síndrome , ÁguaRESUMO
Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.
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Doença das Coronárias , Medicina Tradicional Chinesa , Humanos , Depressão/diagnóstico , Doença das Coronárias/diagnóstico , Muco , Síndrome , AnsiedadeRESUMO
BACKGROUND: Coronary heart disease(CHD) with stable angina pectoris is a common cardiovascular disease. It has been reported that 10%-81.4% of these patients suffer from psychological conditions,such as depression, which has been associated with more frequent angina, lower treatment satisfaction and lower perceived quality of life. Ginkgo biloba extract (GBE), the raw material of Ginkgo biloba dropping pills (GBDPs), is widely used to treat various conditions, including cardiovascular disease, ischaemic cerebrovascular disease, and depression. This clinical trial aimed to examine the efficacy and safety of GBDPs in improving the frequency of angina pectoris and the life quality of patients with stable angina pectoris and depression symptoms. METHODS: This randomised, double-blind, placebo-controlled, parallel-group and multicentre clinical trial will be conducted in four medical centres in China. We aim to recruit approximately 72 participants aged 18-75 years with depression and coronary heart disease with stable angina pectoris. Based on conventional drug treatment, participants will be randomly assignedto the treatment group (GBDPs group; n=36) or the control group (placebo group; n=36) at a 1:1 allocation ratio. After randomisation,follow-up will be done at 4 weeks, 8 weeks and 12 weeks (±3 days). Additionally, 30 healthy individuals will be enrolled to investigate the underlying pharmacological mechanisms of the effects of GBE. The primary outcomes will be the Seattle Angina Questionnaire score and the frequency of angina pectoris-related symptoms each week. The secondary outcomes will include the 36-item Short Form Health Survey quality-of-life scale, Hamilton Depression Scale and composite endpoint incidence of major adverse cardiovascular events. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYECK [2020]030). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04529148 and ChiCTR2200066908.
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Angina Estável , Doença das Coronárias , Medicamentos de Ervas Chinesas , Humanos , Angina Estável/tratamento farmacológico , Ginkgo biloba , Medicamentos de Ervas Chinesas/farmacologia , Grupos Controle , Depressão/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento , Método Duplo-Cego , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.
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Aterosclerose , Doença das Coronárias , Humanos , Medicina Tradicional Chinesa , Muco , LipídeosRESUMO
Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.
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Catecóis , Produtos Finais de Glicação Avançada , Animais , Camundongos , Autofagia , Catecóis/farmacologia , Fibrose , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Transição Epitelial-MesenquimalRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cardiorenal syndrome type 4 (CRS type 4), with high rates of morbidity and mortality, has become a social and economic problem worldwide over the last few decades. Zhen-Wu decoction, a traditional medicine used in East Asia, has been widely used in the treatment of cardiovascular disease and kidney disease, and has shown potential therapeutic effects for the clinical treatment of CRS type 4. However, the underlying mechanism has not been extensively explored. AIM OF THE STUDY: The purpose of this study was to investigate the effect and underlying mechanism of Zhen-Wu decoction on uremic cardiomyopathy, offering a potential target for clinical treatment of CRS type 4. MATERIALS AND METHODS: Five/six nephrectomized mice were utilized for experiments in vivo. The cardioprotective effects of Zhen-Wu decoction were evaluated by echocardiography and tissue staining. RNA-Seq data were used to investigate the potential pharmacological mechanism. The prediction of targets and active components was based on our previous strategy. Subsequently, the protective effect of the selected compound was verified in experiments in vitro. RESULTS: Zhen-Wu decoction alleviated cardiac dysfunction and endothelial injury in 5/6 nephrectomized mice, and the mechanism may involve the inflammatory process and oxidative stress. The activation of the Nrf2 signaling pathway was predicted to be a potential target of Zhen-Wu decoction in protecting endothelial cells. Through our machine learning strategy, we found that lactiflorin as an ingredient in Zhen-Wu decoction, alleviates IS-induced endothelial cell injury by blocking Keap1 and activating Nrf2. CONCLUSIONS: The present study demonstrated that Zhen-Wu decoction and lactiflorin could protect endothelial cells against oxidative stress in mice after nephrectomy by activating the Nrf2 signaling pathway.
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Medicamentos de Ervas Chinesas , Uremia , Animais , Simulação por Computador , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/metabolismo , Glicosídeos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Monoterpenos , Fator 2 Relacionado a NF-E2/metabolismo , Uremia/tratamento farmacológicoRESUMO
BACKGROUND: Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted. METHODS AND RESULTS: Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFß1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling. CONCLUSIONS: The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Coração , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Farmacologia em Rede , Ratos , Remodelação VentricularRESUMO
BACKGROUND: Sepsis-induced myopathy (SIM) is a disease that causes motor dysfunction in patients with sepsis. There is currently no targeted treatment for this disease. Acupuncture has shown considerable efficacy in the treatment of sepsis and muscle weakness. Therefore, our research aims to explore the effects of acupuncture on the improvement of muscle structure and function in SIM patients and on activities of daily living. METHODS: The ACU-SIM pilot study is a single-center, propensity-score stratified, assessor-blinded, prospective pragmatic controlled trial (pCT) with a 1-year follow-up period. This study will be deployed in a multi-professional critical care department at a tertiary teaching hospital in Guangzhou, China. Ninety-eight intensive care unit subjects will be recruited and assigned to either the control group or the acupuncture group. Both groups will receive basic treatment for sepsis, and the acupuncture group will additionally receive acupuncture treatment. The primary outcomes will be the rectus femoris cross-sectional area, the Medical Research Council sum-score and time-to-event (defined as all-cause mortality or unplanned readmission to the intensive care unit due to invasive ventilation). The activities of daily living will be accessed by the motor item of the Functional Independence Measure. Recruitment will last for 2 years, and each patient will have a 1-year follow-up after the intervention. DISCUSSION: There is currently no research on the therapeutic effects of acupuncture on SIM. The results of this study may contribute to new knowledge regarding early muscle atrophy and the treatment effect of acupuncture in SIM patients, and the results may also direct new approaches and interventions in these patients. This trial will serve as a pilot study for an upcoming multicenter real-world study. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR-1900026308, registered on September 29th, 2019.
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Terapia por Acupuntura/métodos , Debilidade Muscular/terapia , Atrofia Muscular/terapia , Doenças Musculares/terapia , Sepse/terapia , Atividades Cotidianas , Terapia por Acupuntura/efeitos adversos , China/epidemiologia , Cuidados Críticos/organização & administração , Seguimentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Mortalidade/tendências , Debilidade Muscular/etiologia , Debilidade Muscular/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Doenças Musculares/etiologia , Readmissão do Paciente/tendências , Projetos Piloto , Pontuação de Propensão , Estudos Prospectivos , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Sepse/complicações , Centros de Atenção Terciária/organização & administração , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the rules of acupoint selection and drug use in treatment of hypertension with acupoint application therapy. METHODS: The articles of the clinical research of hypertension treated with acupoint application therapy were retrieved from Chinese journal full-text database (CNKI), VIP database (VIP) and Wanfang databases from the time of establishment to January 20, 2019. The database was set up with Microsoft Excel 2010. Using the cloud platform of the ancient and modern medicine record, the frequency statistical and clustering analyses were conducted. RESULTS: A total of 117 articles were collected, including 191 prescriptions, 60 aucpoints and 236 kinds of herbal drugs. It was found in the frequency statistical analysis that the top 6 acupoints in use frequency were Yongquan (KI 1), Quchi (LI 11), Taichong (LR 3), Shenque (CV 8), Sanyinjiao (SP 6) and Neiguan (PC 6). According to the correlation analysis, corresponding to these top 6 acupoints, the pairs of acupoints were Sanyinjiao (SP 6) and Yongquan (KI 1), Shenque (CV 8) and Yongquan (KI 1), Neiguan (PC 6) and Yongquan (KI 1), Zusanli (ST 36) and Sanyinjiao (SP 6), Sanyinjiao (SP 6) and Neiguan (PC 6) with Yongquan (KI 1), as well as Yongquan (KI 1) and Neiguan (PC 6) with Sanyinjiao (SP 6). The dominant meridians were the kidney meridian, the conception vessel and the bladder meridian. The special acupoints referred to yuan-source point, luo-connecting point, back-shu point and front-mu point. The top 3 herbal drugs in use frequency included fructus evodiae, semen sinapis and rhizoma chuanxiong. The herbs used were mainly warm and slight cold in nature and neutral in property. The frequencies of the drug use were similar in the application for cold and heat purposes. The common flavors of the herbal medicines were pungent, sweat and bitter and the liver, kidney and spleen meridians were generally involved in meridian tropism. CONCLUSION: In treatment of hypertension with acupoint application therapy, the commonly used single acupoint is Yongquan (KI 1), which is generally combined with Sanyinjiao (SP 6), Shenque (CV 8), Neiguan (PC 6) and Zusanli (ST 36). The correlation is emphasized on the application of special acupoints, meridian points and zangfu organs. The vesicatory herbal drugs are predominant in the drug use. In generally, this therapy embodies the treatment principles as tonifying for the deficiency and reducing for the excess, as well as balancing of cold and heat.
Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Hipertensão/terapia , Meridianos , HumanosRESUMO
Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.
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BACKGROUND AND PURPOSE: Liquorice is the root of Glycyrrhiza glabra, which is a popular food in Europe and China that has previously shown benefits for skeletal fatigue and nutrient metabolism. However, the mechanism and active ingredients remain largely unclear. The aim of this study was to investigate the active ingredients of liquorice for muscle wasting and elucidate the underlying mechanisms. EXPERIMENTAL APPROACH: RNA-Seq and bioinformatics analysis were applied to predict the main target of liquorice. A machine learning model and a docking tool were used to predict active ingredients. Isotope labelling experiments, immunostaining, Western blots, qRT-PCR, ChIP-PCR and luciferase reporters were utilized to test the pharmacological effects in vitro and in vivo. The reverse effects were verified through recombination-based overexpression. KEY RESULTS: The liposoluble constituents of liquorice improved muscle wasting by inhibiting protein catabolism and fibre atrophy. We further identified FoxO1 as the target of liposoluble constituents of liquorice. In addition, hispaglabridin B (HB) was predicted as an inhibitor of FoxO1. Further studies determined that HB improved muscle wasting by inhibiting catabolism in vivo and in vitro. HB also markedly suppressed the transcriptional activity of FoxO1, with decreased expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. CONCLUSIONS AND IMPLICATIONS: HB can serve as a novel natural food extract for preventing muscle wasting in chronic kidney disease and possibly other catabolic conditions.
Assuntos
Benzopiranos/farmacologia , Biologia Computacional , Proteína Forkhead Box O1/antagonistas & inibidores , Glycyrrhiza/química , Aprendizado de Máquina , Extratos Vegetais/farmacologia , Animais , Benzopiranos/química , Benzopiranos/isolamento & purificação , Relação Dose-Resposta a Droga , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Relação Estrutura-Atividade , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genéticaRESUMO
OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).
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Aerossóis/uso terapêutico , Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Aerossóis/efeitos adversos , Estudos de Casos e Controles , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
We aimed to examine the effects of zinc supplementation on nutritional status, lipid profile, and antioxidant and anti-inflammatory therapies in maintenance hemodialysis (MHD) patients. We performed a systematic review and meta-analysis of randomized, controlled clinical trials of zinc supplementation. Metaregression analyses were utilized to determine the cause of discrepancy. Begg and Egger tests were performed to assess publication bias. Subgroup analysis was utilized to investigate the effects of zinc supplementation in certain conditions. In the crude pooled results, we found that zinc supplementation resulted in higher serum zinc levels (weighted mean difference [WMD] = 28.489; P < 0.001), higher dietary protein intake (WMD = 8.012; P < 0.001), higher superoxide dismutase levels (WMD = 357.568; P = 0.001), and lower levels of C-reactive protein (WMD = -8.618; P = 0.015) and malondialdehyde (WMD = -1.275; P < 0.001). The results showed no differences in lipid profile. In the metaregression analysis, we found that serum zinc levels correlated positively with intervention time (ß = 0.272; P = 0.042) and varied greatly by ethnicity (P = 0.023). Results from Begg and Egger tests showed that there was no significant bias in our meta-analysis (P > 0.1). Results of subgroup analysis supported the above results. Our analysis shows that zinc supplementation may benefit the nutritional status of MHD patients and show a time-effect relationship.
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Suplementos Nutricionais , Metabolismo dos Lipídeos/efeitos dos fármacos , Diálise Renal , Zinco/uso terapêutico , Antioxidantes/uso terapêutico , Proteína C-Reativa/metabolismo , Humanos , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Zinco/sangueRESUMO
OBJECTIVE: To investigate the expressions of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) mRNA and miR-25-3p/5p in myocardium of rats with heart failure and the therapeutic effects of Xiefei Lishui recipe(Traditional Chinese Medicine). METHODS: SD rats were randomly divided into five groups:control group, model group, Traditional Chinese Medicine group(TCM group), captopril group and digoxin group(n=10). Heart failure rat model was induced by intraperitoneal injections of doxorubicin(6 injections within 2 weeks; total dose:15 mg/kg). Five weeks after the first injection, Distilled water(10 ml/(kg·d)), TCM(22 g/(kg·d)), captopril(19 mg/(kg·d)),and digoxin(32µg/(kg·d))were administrated by gastrogavage for 35 days,respectively. Myocardial expressions of SERCA2a mRNA and miR-25-3p/5p were detected;myocardial activities of SERCA2a were measured; cardiac output(CO) and left ventricular ejection fraction(LVEF) and plasma level of B-type natriuretic peptide (BNP) were measured. RESULTS: Myocardial mRNA expression of SERCA2a was significantly down-regulated in rats with heart failure which could be significantly up-regulated by TCM or captopril or digoxin,while expressions of miR-25-3p and miR-25-5p in myocardium were significantly up-regulated which could be significantly down-regulated by TCM or captopril. SERCA2a activity, CO and LVEF in rats with heart failure were decreased significantly which could be significantly increased by TCM,while plasma level of BNP was increased significantly which could be significantly decreased by TCM or captopril or digoxin. CO in rats with heart failure could be signifi-cantly increased by captopril or digoxin. CONCLUSIONS: In rats with heart failure, myocardial mRNA expression of SERCA2a was downregulated, expression of miR-25-3p and miR-25-5p in myocardium was upregulated. Xiefei Lishui recipecan upregulate myocardial mRNA expression of SERCA2a, downregulate expression of miR-25-3p and miR-25-5p in myocardium and improve cardiac function.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , MicroRNAs/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Animais , Captopril/farmacologia , Débito Cardíaco , Digoxina/farmacologia , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/sangue , Ratos , Ratos Sprague-Dawley , Volume SistólicoRESUMO
OBJECTIVES: To investigate the safety and efficacy of yangxinkang tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention. METHODS: In a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment. RESULTS: Totally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P<0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P<0.01), which were significantly lower than those in the control group (P<0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P<0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P<0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P>0.05). There was no obvious adverse reaction in either group noted during the study. CONCLUSIONS: Yangxinkang tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.
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Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Doença Crônica , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Qualidade de Vida , Inquéritos e Questionários , ComprimidosRESUMO
This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.
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Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Fibras Colinérgicas/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Ácido Ibotênico , Nootrópicos/farmacologia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fibras Colinérgicas/metabolismo , Colinesterases/metabolismo , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso , Ratos Sprague-Dawley , Receptor trkA/metabolismo , Receptores de Fatores de Crescimento , Receptores de Fator de Crescimento Neural/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Fatores de TempoRESUMO
It is of vital significance to conduct active postmarketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China Food and Drug Administration. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The expert consensus for postmarketing surveillance focuses on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.
RESUMO
OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.
Assuntos
Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Óleos Voláteis/uso terapêutico , Fitoterapia , Idoso , Doença das Coronárias/tratamento farmacológico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
It is of vital significance to conduct active post-marketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China food and drug administration. The standards for technological specifications based on expert consensus have been drafted. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The technological specifications for post-marketing surveillance focus on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.