RESUMO
The purpose of this study was to observe the effect of Inonotus obliquus polysaccharide (IOP) on blood lipids and its regulation on the intestinal flora in hyperlipidemia rats, and explore the modern biological connotation of IOP in reducing blood lipids. In this study, we obtained the crude IOP by the water extraction and alcohol precipitation method, and then classified it by DEAE ion-exchange chromatography to obtain the acidic I. obliquus polysaccharide (IOP-A). After the administration of the IOP-A, the serum TC, TG, and LDL-C levels were significantly lower, while the serum HDL-C levels were significantly higher. The expression of CYP7A1 protein was considerably increased, whereas the expression of SREBP-1C protein was considerably decreased in the rat hepatic tissue. In addition, the IOP-A could significantly alleviate the hepatocyte fatty degeneration in the liver lobule of rats. We believe that the IOP-A can affect the composition of intestinal flora by reducing the relative abundance of Firmicutes and increasing the relative abundance of Bacteroidetes. These findings indicated that the IOP-A can regulate the dyslipidemia of hyperlipidemia rats, and its mechanism may be through regulating the CYP7A1 and SREBP-1C expression in the metabolism of lipids, and correcting the imbalance of intestinal flora structure caused by a high-fat diet.
RESUMO
The aim of this study was to optimize the separation and purification technology of water-soluble Ginkgo biloba leaves polysaccharides (WGBP), analyze its composition characteristics, observe its hair-growth promoting effect in alopecia areata mice, clarify the polysaccharide fraction with bioactive activities, and explore its anti-inflammation mechanism. We isolated acidic polysaccharides (WGBP-A2) and purified a RG-I type polysaccharide (WGBP-A2b) with a molecular weight of 44 kDa. Results showed that WGBP-A2 could significantly increase the contents of VEGF and HGF in the skin tissue of alopecia areata mice, decrease the contents of Inflammatory factors in the serum. On a cellular level, the expressions of p-p65 and p-IκBα, TNF-α and IL-1ß in HUVECs treated with WGBP-A2b were down-regulated. The bioinformatic analysis showed that the inflammation signaling pathway was significantly changed. Its specific mechanism may be related to its regulating the expression of p-p65 p-IκBα, TNF-α and IL-1ß proteins in the inflammation signaling pathway.
Assuntos
Ginkgo biloba/química , Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Cabelo/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificaçãoRESUMO
BACKGROUND: Osteoporosis attacks approximately 10% of the population worldwide. Sika Deer (Cervus nippon), one of China's precious traditional medicinal animals, has been widely recorded in ancient Chinese medical books and claimed for centuries to have numerous medical benefits including bone strengthening. This study aimed to find the use of Sika Deer bone in treating osteoporosis according to traditional records and to investigate the protective effect of Sika Deer bone polypeptide extract on glucocorticoidinduced osteoporosis (GIOP) in rats. RESULTS: Sika Deer bone polypeptide extract could increase serum Ca2+ and BGP, decrease serum P3+, ALP, PTH, and CT, but had no effect on serum NO in rats with GIOP. The immunohistochemical iNOS results of the rats' distal femur were negative in each group. Besides the model group, the eNOS color reaction in osteoblasts was strongly positive in the other three groups. CONCLUSIONS: Sika Deer bone polypeptide extract can improve pathological changes in the microstructure and stimulate the expression of eNOS in osteoblasts. The protective effect on bone might be mediated by eNOS-dependent NO generation.
Assuntos
Animais , Masculino , Ratos , Osteoporose/prevenção & controle , Peptídeos/farmacologia , Osso e Ossos/metabolismo , Cervos , Osteoblastos , Dexametasona , Ratos Wistar , Óxido Nítrico Sintase Tipo III/efeitos dos fármacosRESUMO
The preventive and therapeutic mechanisms of CDBE on osteoporosis were studied by observing the serum bone-related biochemical indicators, bone trabecular micro-structure and intestinal flora in ovariectomized osteoporosis model mice, in order to provide a scientific theoretical basis for the further study on the effect of CDBE on osteoporosis, and the prevention and treatment of osteoporosis with clinical traditional Chinese medicines. The components in CDBE were detected by UHPLC-MS. A mouse osteoporosis model was established by the bilateral ovariectomy in female ICR mice. The biochemical indicators related to osteoporosis were detected, the right proximal tibia was scanned by Micro-CT, the intestinal microflora in the colon contents were examined, and the changes of microflora were taken as the main target to evaluate the effect of CDBE on the intestinal microflora in the model mice. A total of 16 compounds were obtained by the combined application of UHPLC-MS. CDBE could significantly increase the contents of E2, Ca2+ , CT, HyP, OCN, FOXP3, P1NP and CTX-II, in the model mice. CDBE could significantly improve the trabecular micro-structure, Tb.N, Tb.Sp, SMI and Conn.D. CDBE could make the intestinal flora of osteoporosis model mice tend to healthy mice in species and quantity. CDBE can improve the symptoms of postmenopausal osteoporosis in mice, with a positive effect on the intestinal flora of postmenopausal mice. Its mechanism of regulating the symptoms of osteoporosis may be related to the regulation of bone-related biochemical indicators in the serum of mice. PRACTICAL APPLICATIONS: This research has a positive impact on the development of functional food with anti-osteoporosis in the future.
Assuntos
Cervos , Microbioma Gastrointestinal , Osteoporose , Animais , Densidade Óssea , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Osteoporose/tratamento farmacológico , Extratos Vegetais , Ratos , Ratos Sprague-DawleyRESUMO
This experiment mainly optimized the extraction technology of Agaricus blazei polypeptide (ABp) and evaluated its protective effect on aging mice. In this study, a novel single component, the M is 3 kD, was isolated and purified from Agaricus blazei. An aging mouse model was established using D-galactose. After the administration of ABp, the contents of total antioxidant capacity (T-AOC), malondialdehyde (MDA), catalase (CAT), and reactive oxygen species were significantly changed. Through immunofluorescence staining, it was observed that ABp can reduce changes in brain tissue. The differential expression of genes was analyzed by RNA-seq. A total of 295 differentially expressed genes were screened out in the ABp group.RT-qPCR verified important genes and showed that the mRNA expression levels of Hsph1, Trim32, HK1, Hnrnpa1, and Grik5 were significantly increased, and those of ApoE, Atp1a3, Stxbp1, and Mapk8ip1 was significantly decreased. Western blotting showed that the protein expression levels of Keap1 and p53 were significantly lower, while the protein expression levels of Nrf2, HO-1, Hsph1, and Trim32 were significantly higher in the ABP group. ABp played an anti-aging role in an aging mouse model. The specific mechanism of action may be related to the regulation of the expression of the Keap1/Nrf2/P53 signaling pathway and related factors. PRACTICAL APPLICATIONS: The research may contribute to the development of ABp as functional foods or dietary supplements for anti-aging in the future.
Assuntos
Agaricus , Envelhecimento , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Agaricus/metabolismo , Animais , Galactose , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Camundongos , Proteínas Munc18 , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , ATPase Trocadora de Sódio-Potássio , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína LigasesRESUMO
The present research envisaged the effects of Agaricus blazei Murrill polysaccharides (ABPs) on blood lipids and its role in regulation of the intestinal microflora in hyperlipidemic rats. The acidic polysaccharide fraction of Agaricus blazei Murrill was obtained by DEAE-cellulose ion exchange column chromatography. The sugar content of ABP was 75.1%. Compared with the model group (MG), the serum TC, TG, and LDL-C levels decreased (p < .05 or p < .01) and the HDL-C levels increased (p < .01) significantly in the ABP group. Expression of CYP7A1 was up-regulated (p < .01), and that of SREBP-1C (p < .05) was down-regulated significantly in the liver tissue of rats in the ABP group. Additionally, the disordered hepatic lobules and the steatosis of hepatocytes were found to be significantly alleviated in the ABP group. We believe that ABP can reduce the ratio of Firmicutes/Bacteroidetes and reduce the relative abundance of Firmicutes, Ruminococcaceae_unclassified, and Ruminococcaceae, increasing the relative abundance of Proteobacteria, Clostridium_sensu_stricto, Allobaculum, Peptostreptococcaceae, Clostridiaceae_1, and Erysipelotrichaceae as targets to regulate blood lipids. The results showed ABP could regulate the dyslipidemia in rats with hyperlipidemia. The mechanism may be through the regulation of the imbalance of intestinal microflora induced by the high-fat diet in rats, which may be one of the important ways of its intervention on the dyslipidemia induced by high-fat diet.
RESUMO
BACKGROUND: The pathogenesis of the abnormality of the immune system is still not clear at present. Chemosynthetic drugs, human or animal immune products and microbiological drugs are used as the main drugs in clinics currently, but these drugs have different side effects. So researchers turned to safer natural products in order to find immunomodulatory active substances from natural products and their extracts. METHODS: Immunosuppressed mice were induced by cyclophosphamide and administered with Cordyceps militaris polypeptide (CMP) for the study on the effect of CMP on the immune function of mice and its mechanism. Based on the 1748 differential gene sets selected in our previous work, the transcription factors and their corresponding target genes were screened by integrating the TRED (Transcriptional Regulatory Element Database), a transcriptional factor-target gene regulatory network was constructed, then the role of transcription factors in the regulatory network was elucidated by statistically analyzing the key nodes, and finally, the correlation of network genes with diseases was analyzed by using the DAVID database. RESULTS: The results of animal experiments showed that CMP could increase the immune organ indexes, the number of white blood cells, the degree of delayed allergy and the content of hemolysin in the serum of mice. CMP was found to be involved in the regulation of immune function in mice through genes Kdr, Spp1, Ptgs2, Rel, and Smad3, and transcription factors Ets1, E2f2 and E2f1. E2F2 and E2F1 are members of the E2F family, so we speculated that the E2F family might play an important role, and its main regulatory pathways were the PI3K-Akt signaling pathway and TNF signaling pathway. CONCLUSION: CMP can improve the immunity of mice. CMP can regulate the immune function of mice through multiple genes and transcription factors, and may also play a role in immune-related diseases, such as cancer.
Assuntos
Cordyceps/metabolismo , Imunomodulação , Peptídeos/farmacologia , Fatores de Transcrição/genética , Animais , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Ciclofosfamida/toxicidade , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F2/genética , Fator de Transcrição E2F2/metabolismo , Regulação da Expressão Gênica , Genes rel , Proteínas Hemolisinas/sangue , Fenômenos do Sistema Imunitário , Hospedeiro Imunocomprometido/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteopontina/genética , Osteopontina/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo , Fatores de Transcrição/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Polysaccharides are important active constituents of Agaricus blazei Morrill. In the present study, WABM-A was isolated from WABM using DEAE-cellulose, and subsequently purified using sepharose CL-6B to obtain the acidic polysaccharide WABM-A-b. WABM-A-b is mainly composed of Glc dextran, with a molecular weight of 10 KDa and ß-1,6-D-Glcp as its main chain. The results of in vivo experiments show that in comparison with the MG, WABM-A significantly reduced the serum levels of TC, TG, and LDL-C, increased the serum levels of HDL-C (P < 0.01), and upregulated the liver expression of PPARγ, LXRα, ABCA1, and ABCG1 in rats with hyperlipidemia (P < 0.05). The results of in vitro experiments show that in comparison with the MG group, WABM-A-b-H significantly reduced the levels of TC and TG in HepG2 cells induced by oleic acid (P < 0.01), and significantly upregulated the protein expression of PPARγ, LXRα, ABCA1, and ABCG1 (P < 0.05). The present study demonstrates that WABM-A-b is an acidic glucan with lipid-lowering activity. The lipid-lowering mechanism of WABM-A-b is via the activation of the PPARγ/LXRα/ABCA1/ABCG1 cholesterol metabolism pathway. This is the first time that the hypolipidemic effect of Agaricus blazei Morrill acidic polysaccharides has been reported.
Assuntos
Agaricus/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular , Modelos Animais de Doenças , Glucanos , Células Hep G2 , Humanos , Hiperlipidemias/tratamento farmacológico , Fígado/patologia , Masculino , Ácido Oleico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Cordyceps militaris (L.) Link (C. militaris) has been used as a folk medicine for treatment of various diseases in China and some other countries. Recent evidence suggests that aqueous extracts of C. militaris have hypoglycemic activity. So the aim of this study was to isolate and characterize compounds with aiti-PTP1B (protein tyrosine phosphatase 1B) activity from C. militaris. As a result, cordycerebroside B (1) together with other three known cerebrosides (2-4) and a disaccharide (5) were isolated by silica gel column chromatography and semi-preparative high performance liquid chromatography (HPLC) and then elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and chemical method. Among of which, cordycerebroside B was a new compound and isolated from C. militaris for the first time. The results of the activity assays demonstrated that all these four cerebrosides (compounds 1-4) showed marked inhibition activity against PTP1B with IC50 values of 4.68⯱â¯0.18, 16.93⯱â¯1.08, 10.43⯱â¯0.64 and 18.92⯱â¯1.65⯵M. All the compounds had no discernible cytotoxicity for Rat pheochromocytoma (PC12 cells). These findings suggested that C. militaris or its cerebrosides may be considered as potential useful therapeutic agents for type 2 diabetes.
Assuntos
Cerebrosídeos/farmacologia , Cordyceps/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Cerebrosídeos/isolamento & purificação , China , Carpóforos/química , Estrutura Molecular , Células PC12 , Ratos , Testes de ToxicidadeRESUMO
Osteosarcoma (OS) is a malignant primary bone tumor with high metastatic rate. C-X-C motif chemokine ligand 6 (CXCL6) and its receptor C-X-C motif chemokine receptor 1/2 (CXCR1/2) have been found to participate in the process of carcinogenesis. In this study, we evaluated the role of CXCL6/CXCR1/2 axis in proliferation and metastasis of OS cells. According to our results, the mRNA and protein expressions of CXCL6, CXCR1, and CXCR2 in multiple OS cell lines were determined. Treatment with exogenous CXCL6 for more than 72 h significantly promoted the proliferation of OS cells. Blocking the effect of endogenous CXCL6 restrained the migration, invasion and epithelial-mesenchymal transition (EMT) as evidenced by increased E-cadherin level, decreased N-cadherin and Snail levels in OS cells. On the contrary, exogenous CXCL6 administration enhanced the migration and invasive abilities of OS cells. Moreover, silencing of CXCR1/2 suppressed migration, invasion and EMT of OS cells with or without treatment with exogenous CXCL6. In addition, exogenous CXCL6 promoted the activation of PI3K/AKT and ß-catenin signaling pathways, which could be repressed by CXCR2 knockdown. Inactivation of PI3K/AKT or ß-catenin pathway by specific inhibitors effectively suppressed CXCL6-induced migration, invasion and EMT of OS cells. Finally, overexpression of CXCL6 significantly contributed to tumor growth, pulmonary metastasis and activation of PI3K/AKT and ß-catenin pathways in nude mice in vivo, which were repressed by treatment with CXCR2 antagonist. Our results suggest that CXCL6/CXCR1/2 axis promotes the proliferation and metastasis of OS cells.
RESUMO
[This corrects the article DOI: 10.3892/etm.2018.6422.].
RESUMO
The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic potential in metastatic human hepatocarcinoma, possibly through the modulation of matrix metalloproteinase-2 expression. The purpose of the present study was to evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse model. The inhibitory effect on the growth of mouse ascites tumors was monitored by measuring body weight gain, survival time, ascites volume, numbers of tumor cells, DNA synthesis and peritoneal capillary permeability analysis. The present data revealed a significant reduction in ascites volume and cell count in mice that were treated with P-5m plus 5-Fu. Furthermore, the median survival time in mice in the combination group was prolonged compared with the disease control group. Moreover, a significant reduction in the total H22 ascites cell count in mice from the combination group was observed when compared with the disease control group. P-5m plus 5-Fu was able to induce the cell cycle arrest and inhibit the peritoneal capillary permeability of the mice. To conclude, the present study indicated that P-5m may have therapeutic potential in ascites caused by hepatocellular carcinoma.
RESUMO
Our previous research revealed that Cordyceps militaris can improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by which Cordyceps militaris improves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects of Cordyceps polypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes Pik3r5, Il-1ß, and Slc18a2 were involved in the effects of Cordyceps polypeptide on the nervous system of these mice. Our findings suggest that Cordyceps polypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system.
RESUMO
Our previous study found that Deproteinized Extract of Calf Blood (DECB) could protect the acute liver injury induced by carbon tetrachloride in mice, but the target-related transcription factors and their regulatory networks were not comprehensively studied. Based on the mRNA expression microarray data obtained in the previous study, the mRNA transcription factor regulatory networks were constructed by screening the transcription factors of differentially expressed genes and their corresponding target proteins, and the analysis on the functions and pathways of the regulatory network central nodes was performed. Eight genes Ltf, Tnf, Il6, Jun, Il12b, Stat3, Rel and Crem could regulate the inflammatory factors, and TNF signaling pathway and Jak-STAT signaling pathway might play an important role in the mechanism through which DECB protected the liver of mice. DECB can not only inhibit the apoptosis of hepatocytes, but also inhibit the inflammatory cytokines.
Assuntos
Extratos Celulares/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Hepatócitos/fisiologia , Animais , Sangue/metabolismo , Tetracloreto de Carbono , Bovinos , Extratos Celulares/química , Citoproteção/genética , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Janus Quinases/metabolismo , Camundongos , Análise em Microsséries , RNA Mensageiro/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Ativação Transcricional , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: About thirty thousand people globally die every day from infectious diarrhea, mostly caused by pathogenic Escherichia coli (E. coli) O157:H7. METHODS: In order to search for clinical diagnostic biomarkers and novel drug targets for infectious diarrhea, we used a bibliometric method to collect pathogenic genes of E. coli O157:H7 and performed a functional analysis of the important pathogenic genes by pathway enrichment and operon analysis. RESULTS: We found 364 pathogenic genes which may be involved in infection with E. coli O157:H7 including 50 new specific pathogenic genes. It is possible that these newly found pathogenic genes will be of great importance in the treatment of E. coli O157:H7 infected diseases and the discovery of novel diagnostic biomarkers. CONCLUSIONS: Our findings also lay a theoretical foundation for the control, diagnosis, and prognosis of pathogenic E. coli related diseases.
Assuntos
Infecções por Escherichia coli , Escherichia coli O157 , Infecções por Escherichia coli/genética , Escherichia coli O157/genética , Escherichia coli O157/patogenicidade , Genes Bacterianos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Programas de Rastreamento , Óperon , Análise de Sequência de DNARESUMO
Liver injury is a common pathological basis of various liver diseases, and long-term liver injury is often an important initiation factor leading to liver fibrosis and even liver cirrhosis and hepatocellular carcinoma (HCC). It has been reported that deproteinized extract of calf blood (DECB) can inhibit the replication of hepatitis B virus and confers a protective effect on the liver after traumatic liver injury. However, few studies on the regulatory factors and mechanisms of DECB have been reported. In this current study, an acute mouse liver injury model was established with carbon tetrachloride (CCl4). The differentially expressed genes and related cell signal transduction pathways were screened using mRNA expression microarray. STEM software V1.3.6 was used for clustering gene functions, and the DAVID and KEGG databases were applied for the analysis. A total of 1355 differentially expressed genes were selected, among which nine were validated by RT-qPCR. The results showed that the Fas, IL1b, Pik3r1, Pik3r5, Traf2, Traf2, Csf2rb2, Map3k14, Pik3cd and Ppp3cc genes were involved in the regulation of DECB in an acute mouse liver injury model. Targets of the protective effects of DECB and its related mechanisms were found in mice with acute liver injury induced by carbon tetrachloride, which may provide an important theoretical basis for further DECB research.
Assuntos
Tetracloreto de Carbono , Fígado , Actiemil , Animais , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Western Blotting , Tetracloreto de Carbono/toxicidade , Modelos Animais de Doenças , Fígado/lesões , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , SoftwareRESUMO
In this paper, a selenium polysaccharide (PGP1) was isolated from the radix of Platycodon grandiflorum. We investigated the protective capacity of PGP1 against the hydrogen peroxide (H2O2)-induced oxidative damage in cultured rat pheochromocytoma (PC12) cells. Cells were pretreated with various doses of PGP1 (50, 100 and 200µg/mL) for 24h before exposure to 0.5mM H2O2 for 12h. Cell viability, LDH release, apoptotic rates, malondialdehyde (MDA) content, antioxidant enzyme superoxide dismutase (SOD) activity and intracellular accumulation of reactive oxygen species (ROS) were determined. The results showed pretreatment of PC12 cells with PGP1 prior to H2O2 exposure inhibited the decrease of cell viability, decreased the apoptotic rates, prevented membrane damage (LDH release) and attenuated intracellular ROS formation in PC12 cells injured by H2O2. Meanwhile, PGP1 increased SOD activity, while it decreased the level of MDA and the production of lipid peroxidation, in PC12 cells after H2O2 exposure. These findings suggested that PGP1 may be considered as a potential useful antioxidant agent in reducing neuronal oxidative damage via inhibiting oxidative stress.
Assuntos
Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Platycodon/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Selênio/química , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Malondialdeído/metabolismo , Células PC12 , Ratos , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Tuberculosis (TB) is a serious communicable disease throughout the world. Re-emergence of the TB epidemic is aggravated by the circulation of multidrug-resistant Mycobacterium tuberculosis strains, and more than half of new cases have occurred in Asia. Therefore, it is important to understand the gene mutations underlying the development of rifampicin resistance in Asia. METHODS: In this study, we classified the rifampicin-resistant Mycobacterium tuberculosis (MTB) rpoB data downloaded from Genbank, based on 12 mutation points. The relationship between the mutation sites and regional information was analyzed, after which the mutation dates and mutation trends of the rpoB gene were predicted by the Markov Chain Monte Carlo (MCMC) method. RESULTS: We discovered that the mutation sites of the rpoB gene were disparate in different regions of Asia. The results of this study clearly showed that drug-resistant gene mutations in Asia started to increase in 2000 and peaked in 2006, indicating the relationship between drug resistance and outbreak trends of TB. CONCLUSIONS: From our analysis, it was not difficult to see the relationship between the mutation rates of the rpoB gene and the outbreak of TB. Hence, to some degree, outbreak trends of TB can be predicted through genotyping based on the rpoB gene.
Assuntos
Antibióticos Antituberculose/uso terapêutico , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Evolução Molecular , Modelos Genéticos , Mutação , Mycobacterium tuberculosis/genética , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Ásia , Teorema de Bayes , RNA Polimerases Dirigidas por DNA , Bases de Dados Genéticas , Humanos , Cadeias de Markov , Método de Monte Carlo , Mycobacterium tuberculosis/efeitos dos fármacos , Filogenia , Dinâmica Populacional , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
Purpose: Compound K (CK), the metabolic product of protopanaxadiol saponin in vivo, has many pharmacological activities. In this study, we discuss the preparation of CK, and its protective effect on kidneys of diabetic rats. CK was prepared from ginsenoside Rbt after transformation by 3-glucosidase, separation and purification by silica gel column chromatography. In the present study, we established a rat model of diabetes mellitus using high-fat diet and streptozotocin (STZ). After seven weeks of treatment, the levels of fasting blood glucose (FBG), total cholesterol (TC), total glycerin (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), blood urea nitrogen (BUN), uric acid (UA), serum creatinine (Scr), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) were evaluated in normal and diabetic rats. Also, renal pathomorphism changes were observed by HE stain, and TGF-ß1 protein expression in the renal tissue was measured by Western blot. The yield of CK was 14.55 mg/mL, which was higher than that of other methods. After seven weeks, CK could decrease FBG, TC, TG, LDL-C, BUN, UA, Scr and MDA of diabetic rats, while CK also enhanced HDL-C and GSH, SOD and GSH-PX. Additionally, CK improved the pathological changes and decreased TGF-ß1 protein expression in the renal tissue. CK improved the pathological changes in the renal tissue, enhanced the antioxidant capacity, reduced the damage of TGF-ß1 to renal tissue, and protected the diabetic rats.
Assuntos
Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Ginsenosídeos/farmacologia , Animais , Biomarcadores , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Rim/metabolismo , Estrutura Molecular , Panax/química , Ratos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
CONTEXT: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear. OBJECTIVE: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity. MATERIALS AND METHODS: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated. RESULTS: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50 mg/kg b.w., respectively (p < 0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p < 0.05 or p < 0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p < 0.05 or p < 0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p < 0.05 or p < 0.01). DISCUSSION AND CONCLUSION: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.