RESUMO
The lipid metabolism disorder is the key role of Nonalcoholic fatty liver disease (NAFLD). Selenoprotein P plays an important role in the pathological process of lipid accumulation. Coix lacryma-jboi seed oil (CLSO) is an active component extracted from Coix lacryma-jobi seed (CLS) which has been found to be effective of reducing blood fat and antioxidative. But the effect and mechanism of CLSO on NAFLD are not clear. The aim of this study was to explore the therapeutic effect and mechanism of CLSO in the treatment of NAFLD. Our result showed that CLSO decreased the liver/body weight ratio, lowered the total cholesterol (TC) and triacylglycerol (TG), and elevated the high density lipoprotein (HDL) in serum. CLSO reduced the lipid deposition in the liver of NAFLD rats. In addition, CLSO could bring down the abnormal expression of superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, CLSO significantly declined the liver apolipoprotein E (apoE), apolipoprotein E receptor (apoER) and selenoprotein P 1 (SePP1) expression. In vivo, CLSO decreased the lipid droplets and TG level, reduced the protein expression of SePP1, apoER, phosphor-adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) in the cytoplasm of HepG2 cells induced by oleic acid and palmitic acid (OP). At the same time, lipid accumulation was observed in the Sepp1 high expression cells induced by endoplasmic reticulum (ER) activator tunicamycin (Tm). CLSO could identically reduce the protein expression of SePP1, apoER, p-AMPK in the cytoplasm of HepG2 cells induced by Tm. This result not only proved the CLSO had therapeutic effect on NAFLD, but also confirmed its mechanism associated with degrading the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) which led to the decrease of the expression SePP1/apoER2 in order to reduce lipid accumulation. The study suggests CLSO has great medicinal value in treating NAFLD besides its edibility.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes , Coix/química , Proteínas Relacionadas a Receptor de LDL/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Sementes/química , Selenoproteína P/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Animais , Depressão Química , Masculino , Fosforilação/efeitos dos fármacos , Ratos WistarRESUMO
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 fármacosRESUMO
Radix Astragali (RA) herb with warm property and significant "tonifying qi" effects is indicated for the syndrome of internal cold due to Yang deficiency. The purpose of this research was to explore effects of Radix Astragali (RA) through PPAR signaling pathway on gene expression profiles related to energy metabolism in rats with the Yang-deficiency cold (YDC) syndrome, for identifying the pathological mechanism of Yang-deficiency cold (YDC) syndrome and the effects mechanism of RA. The results indicated that RA could significantly increase body weight (BM), cold and heat tendency (CT), overall temperature (OT), rectum temperature (RT), toe temperature (TT), energy intake (EI), and V(O2)/V(CO2) ratio (which indicates basal metabolism, BM) (P<0.05), enhancing the depressed metabolic function in YDC syndrome model rat. Our data also indicated differentially expressed genes (DEGs) related to energy metabolism involving lipids, carbohydrates, and amino acids metabolic process; the expression of CPT-1 and FABP4 (ap2) was improved; PPAR, Glycolysis, Wnt, cAMP, MAPK, AMPK, and fatty acid degradation signaling pathway may be related to energy metabolism. However, the Chinese herbal medicine RA plays a certain role in promoting the metabolism of substances and energy in rats by its warming and beneficial effect. Our results suggest that the mechanism underlying the function of RA may take effect through the regulation of PPAR signaling pathway and related gene expression. Lipids, carbohydrates, and amino acids metabolic process may be affected to adjust the reduced metabolic function in the model animals. In general, results indicate that RA could promote energy metabolism in rats with the YDC syndrome via PPAR signaling pathway regulating the expression of CPT-1 and FABP4 (ap2), which reflected the warm and qi tonifying properties of RA.
RESUMO
BACKGROUND: Neurological deficits is one of the most prevalent clinical manifestation after stroke. The effects of astrocytes activated by electroacupunture (EA) after stroke on the neurological recovery in middle cerebral artery occlusion (MCAO) rats was not clear and definite. OBJECTIVE: Our previous study showed that treatment with EA for 7 days contributed to the activation of astrocytes in MCAO rats. The purposes of this study were to 1) confirm the effects of EA for 14 days on activation of astrocytes in MCAO rats, and 2) test the relationships between activation of astrocytes and neurological functional recovery induced by EA in MCAO rats. METHODS: All rats were randomly divided into five groups: naïve control group, sham control control group, MCAO, MCAO/EAn, MCAO/EAd (nâ=â8, for each group). Rats in MCAO/EAn group received EA treatment at acupoints of Neiguan (PC06). MCAO/EAd group received EA stimulus at acupoints of Diji (SP08). The primary indicators were locomotor recovery, histopathology, immunohistochemistry, RT-PCR and Western blot. RESULTS: The neurological deficit and histopathological improvements and activation of astrocytes were observed after EA treatment at acupoints PC06. Parametric correlation analyses revealed a cubic correlation relationship between activation of astrocytes and neurological recovery of MCAO rats treated with EA. CONCLUSION: EA treatment at the acupoints of Neiguan involved in the regulation of activation of astrocytes, which our data suggested has a cubic correlation relationship with the neurological recovery of MCAO rats.
Assuntos
Astrócitos/fisiologia , Isquemia Encefálica/terapia , Eletroacupuntura , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/terapia , Animais , Astrócitos/patologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Neurogênese/fisiologia , Ratos Wistar , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND: Coix seed has the functions of fortifying the spleen and inhibiting the dampness. However, it remains unclear which Coix seed compositions is responsible for these functions. Previous investigations have revealed that the main compositions of Coix seed are proteins, polysaccharides, oils and starches. The objectives of this study are to explore which is the most effective compositions in fortifying the spleen and examine how Coix seed works in regulating the water transport on the spleen deficiency and wet dampness (SDWD) rat model. MATERIALS AND METHODS: The rats used were divided into (i) control group, (ii) model group, (iii) decoction group, (iv) protein group, (v) polysaccharide group, (vi) oil group and (vii) starch group. The urine volume, the drinking volume and the water loading index in each group were calculated. Agilent 8*60K array was used for microarray-based gene expression analysis. The differential mRNAs related to the transport activity were screened. qRT-PCR was used to validate the mRNA microarray. RESULTS: The results demonstrated that all treatment groups could decrease the dampness of SDWD rats. mRNA microarray had significant effect on the protein group and the polysaccharide group in regulating the water transport, among which the most significant mRNA was Fabp6, Slc51a, Slc51b, Slc11a2, Slc4a10 and AQP3 respectively. CONCLUSION: The compositions of proteins and polysaccharides had the most significant effect in regulating the water transport of SDWD rat model. The contributing mRNA focused on Fabp, Slc and AQP family.
Assuntos
Coix/química , Medicamentos de Ervas Chinesas/administração & dosagem , Baço/efeitos dos fármacos , Esplenopatias/tratamento farmacológico , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Hormônios Gastrointestinais/genética , Hormônios Gastrointestinais/metabolismo , Humanos , Masculino , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Sementes/química , Baço/metabolismo , Baço/fisiopatologia , Esplenopatias/genética , Esplenopatias/metabolismo , Esplenopatias/fisiopatologia , Água/metabolismoRESUMO
Radix Astragali (RA) with slight sweet and warm property is a significant "qi tonifying" herb; it is indicated for the syndrome of dampness stagnancy due to spleen deficiency (DSSD). The purpose of this research was to explore effects of RA and its split components on gene expression profiles related to water metabolism in rats with the DSSD syndrome for identifying components representing property and flavor of RA. The results indicated that RA and its split components, especially polysaccharides component, significantly increased the body weight and the urine volume and decreased the water load index of model rats. Our data also indicated differentially expressed genes (DEGs) related to water metabolism involved secretion, ion transport, water homeostasis, regulation of body fluid levels, and water channel activity; the expression of AQP1, AQP3, AQP4, AQP5, AQP6, and AQP8 was improved; calcium, cAMP, MAPK, PPAR, AMPK, and PI3K-Akt signaling pathway may be related to water metabolism. In general, results indicate that RA and its split components could promote water metabolism in rats with the DSSD syndrome via regulating the expression of AQPs, which reflected sweet-warm properties of RA. Effects of the polysaccharides component are better than others.
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.