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J Ethnopharmacol ; 266: 113404, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32976970


ETHNOPHARMACOLOGICAL RELEVANCE: Danqi Pill, composed of the root of Salvia miltiorrhiza Bunge and the root of Panax notoginseng, is effective in the clinical treatment of myocardial ischemia in coronary heart diseases. A number of studies have shown that autophagy plays an essential role in cardiac function and energy metabolism, and disordered autophagy is associated with the progression of heart failure. However, the effect and mechanism of Danqi pill on autophagy have not been reported yet. AIM OF THE STUDY: This study aims to elucidate whether Danqi pill restores autophagy to protect against HF and its potential mechanism. MATERIALS AND METHODS: Left anterior descending ligation was established to induce an HF rat model, H2O2-stimulated H9C2 cells model was conducted to clarify the effects and potential mechanism of Danqi pill. In vivo, Danqi pill (1.5 g/kg) were orally administered for four weeks and Fenofibrate (10 mg/kg) was selected as a positive group. In vitro, Danqi pill (10-200 µg/mL) was pre-cultured for 24 h and co-cultured with H2O2 stimulation for 4 h. Importantly, transmission electron microscopy and fluorescence GPF-mRFP-LC3 reporter system were combined to monitor autophagy flux. Furtherly, we utilized Compound C, a specific AMPK inhibitor, to validate whether the autophagy was mediated by AMPK-TSC2-mTOR pathway. RESULTS: Danqi pill significantly improved cardiac function and myocardial injury in HF rats. Intriguingly, Danqi pill potently regulated autophagy mainly by promoting the formation of autophagosomes in vivo. Further results demonstrated that expressions of p-AMPK (P < 0.001) and p-TSC2 (P < 0.001) in cardiac tissue were upregulated by Danqi pill, accompanied with downregulation of p-mTOR (P < 0.01) and p-ULK1(P < 0.01). In parallel with the vivo experiment, in vitro study indicated that Danqi pill dramatically restored autophagy flux and regulated expressions of critical autophagy-related molecules. Finally, utilization of Compound C abrogated the effects of Danqi pill on autophagy flux and the expressions of p-TSC2 (P < 0.05), p-mTOR (P < 0.01) and p-ULK1 (P < 0.05). CONCLUSION: Danqi pill could improve cardiac function and protect against cardiomyocytes injury by restoring autophagy via regulating the AMPK-TSC2-mTOR signaling pathway.

Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/prevenção & controle , Infarto do Miocárdio/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/etiologia , Masculino , Infarto do Miocárdio/complicações , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo
J Ethnopharmacol ; 265: 113324, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32890714


ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong (FXST) is a traditional Chinese patent medicine composed of Panax notoginseng (Burkill) F.H.Chen (Araliaceae), Salvia miltiorrhiza Bunge (Lamiaceae), Astragalus propinquus Schischkin (Leguminosae), and Scrophularia ningpoensis Hemsl. (Scrophulariaceae). It has been widely used for the treatment of diabetic retinopathy (DR) and exerts a positive clinical therapeutic effect. AIM OF THE STUDY: The aim of this study was to observe the effect of FXST on diabetic rat retinas and investigate its pharmacological mechanism for improving DR. METHODS: The diabetic rat model was established by intraperitoneal injection of streptozotocin. The rats were divided into a normal group, diabetic group, and FXST group. The rats in the FXST group were treated with FXST by intragastric administration for 12 weeks while other rats were given the same volume of normal saline. The haemodynamic parameters of the central retinal artery in the rats were measured by ultrasound. Haematoxylin-eosin staining was utilised to observe the pathological structural changes in the retina. The apoptosis of retinal nerve cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling. RNA sequencing was used to screen the differentially expressed genes (DEGs), and enrichment analyses were performed. The DEGs were validated through real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The peak systolic velocity, end diastolic velocity, and mean velocity decreased while the resistance index and pulsatility index increased in the diabetic rat retinas. FXST also improved haemodynamics. In contrast with the diabetic group, FXST allayed the disorder and oedema of the retinal structure in addition to reversing the reductions in retinal thickness and retinal ganglion cell number. It also decreased the apoptosis index of retinal cells. A total of 1134 DEGs were identified by RNA sequencing in the FXST group compared to the diabetic group, including 814 upregulated genes and 320 downregulated genes. These genes were enriched in the complement and coagulation cascades as well as the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Several DEGs, including PPAR gamma, perilipin 4, acyl-CoA dehydrogenase long chain, CD55 molecule, and plasminogen activator urokinase, were identified by qRT-PCR, and the results were consistent with the RNA sequencing data. CONCLUSIONS: FXST alleviates DR by improving the haemodynamics and morphological alterations of diabetic rat retinas, which are mediated by complement and coagulation cascades and the PPAR signalling pathway.

Biomed Pharmacother ; 120: 109483, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629252


Lung cancer is the leading cause of cancer-related deaths. Ginsenoside Rg3 is the main ingredient of Ginseng which is used to treat non-small cell lung cancer (NSCLC). It has been found to enhance the efficiency of chemotherapy thereby reducing its side effects. Previous studies found that ginsenoside Rg3 can reduce the occurrence of NSCLC by inducing DNA damage. Yet, its anti-DNA damaging effects and mechanisms in tumor cells are still not fully understood. This study explored the effect of ginsenoside Rg3 on DNA repair and VRK1/P53BP1 signaling pathway. Ginsenoside Rg3 treatment significantly decreased the incidence and invasionin a mouse model of lung cancer induced by urethane. The results of cell survival assay and single cell gel electrophoresis showed that ginsenoside Rg3 protected lung adenocarcinoma cells from DNA damage as well as inhibited the proliferation of tumor cells. Ginsenoside Rg3 increased the mRNA and protein expression of VRK1 in NSCLC cells as measured by RT-qPCR and western blot, respectively. These findings suggests that ginsenoside Rg3 regulates VRK1 signaling. Immunofluorescence assays showed that P53BP1 and VRK1 protein level increased, and the VRK1 protein translocated between the nuclei and cytoplasm. Finally, this conclusion was confirmed by the reverse validation in VRK1-knockdown cells. Taken together, these results show that ginsenoside Rg3 upregulate VRK1 expression and P53BP1 foci formation in response to DNA damage thereby inhibiting the tumorigenesis and viability of cancer cells. These findings reveal the role of Rg3 in lung cancer and provides therapeutic targets for developing new drugs in the prevention and treatment of lung cancer.

Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Ginsenosídeos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Panax/química , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacos
Cell Transplant ; 28(6): 671-683, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30284459


Xiaoshuan enteric-coated capsule (XSECC) is a drug approved by the Chinese State Food and Drug Administration for the treatment of stroke. This study was to investigate the effects of XSECC on white and gray matter injury in a rat model of ischemic stroke by diffusion tensor imaging (DTI) and histopathological analyses. The ischemia was induced by middle cerebral artery occlusion (MCAO). The cerebral blood flow measured by arterial spin labeling was improved by treatment with XSECC on the 3rd, 7th, 14th and 30th days after MCAO. Spatiotemporal white and gray matter changes in MCAO rats were examined with DTI-derived parameters (fractional anisotropy, FA; apparent diffusion coefficient, ADC; axial diffusivity, λ//; radial diffusivity, λ⊥). The increased FA was found in the XSECC treatment group in the corpus callosum, external capsule and internal capsule, linked with the decreased λ//, λ⊥ and ADC on the 3rd day and reduced ADC on the 30th day in the external capsule, suggesting XSECC reduced the axon and myelin damage in white matter after stroke. The relative FA in the striatum, cortex and thalamus in XSECC treatment group was significantly increased on the 3rd, 7th, 14th and 30th days accompanied by the increased λ// on the 3rd day and reduced relative ADC and λ⊥ on the 30th day, indicating that XSECC attenuated cell swelling and membrane damage in the early stage and tissue liquefaction necrosis in the late stage in gray matter after stroke. Additionally, XSECC-treated rats exhibited increased mean fiber length assessed by diffusion tensor tractography. Moreover, histopathological analyses provided evidence that XSECC relieved nerve cell and myelin damage in white and gray matter after stroke. Our research reveals that XSECC could alleviate white and gray matter injury, especially reducing nerve cell damage and promoting the repair of axon and myelin after ischemic stroke.

Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Substância Cinzenta/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Substância Branca/efeitos dos fármacos , Animais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Imagem de Tensor de Difusão , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Masculino , Ratos Sprague-Dawley , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
BMC Complement Altern Med ; 14: 148, 2014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24885228


BACKGROUND: In traditional Chinese medicine, astragalus injection is used to treat diabetic nephropathy (DN). The current study was conducted to determine the effects of astragalus injection on DN by assessing potential modulation of the transforming growth factor beta TGFß/Smad signaling pathway. METHODS: Diabetic, male KKAy mice, aged 14 weeks were randomly divided into a model group and an astragalus treatment group, while age-matched male C57BL/6J mice were selected as controls. The treatment group received daily intraperitoneal injections of astragalus (0.03 ml/10 g.d), while the model group received injections of an equivalent volume of saline. Mice were euthanized after 24 weeks. Serum samples were obtained from animals in each group, and blood glucose, creatinine, and urea nitrogen levels were measured. Tissue samples from the kidney were used for morphometric studies. The expression of TGFß1, TGFßR-Ι, Smad3, and Smad7 were evaluated using reverse transcription-polymerase chain reaction (RT-PCR), and western blot analysis. RESULTS: Mice in the model group became obese, and suffered complications, including hyperglycemia, polyuria, and proteinuria. Astragalus treatment significantly reduced albuminuria, improved renal function, and ameliorated changes in renal histopathology. Moreover, administration of astragalus injection increased Smad7 expression, and inhibited the expression of TGFßR-Ι, Smad3 and its phosphorylation, and decreased the mRNA level of TGFß1. CONCLUSIONS: The TGFß/Smad signaling pathway plays an important role in the development of DN. Administration of astragalus injection could prevent or mitigate DN by rebalancing TGFß/Smad signaling, and could play a protective role in DN-induced renal damage in KKAy mice.

Astrágalo (Planta)/química , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Rim/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Humanos , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/genética , Proteína Smad7/genética , Proteína Smad7/metabolismo