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Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.
Assuntos
Betaína , Disfunção Cognitiva , Camundongos , Masculino , Animais , Humanos , Betaína/efeitos adversos , Betaína/metabolismo , Microglia , Sistema Hipotálamo-Hipofisário , Pandemias , Solução Salina/efeitos adversos , Solução Salina/metabolismo , Sistema Hipófise-Suprarrenal , Hipocampo , Isolamento Social/psicologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamenteRESUMO
Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 µg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 µg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.
Assuntos
Óleos Voláteis , Origanum , Preparações Farmacêuticas , Toxoplasma , Toxoplasmose , Animais , Humanos , Óleos Voláteis/farmacologia , Toxoplasmose/tratamento farmacológicoRESUMO
Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
Assuntos
Antioxidantes/farmacologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Selênio/farmacologia , Selenoproteína W/metabolismo , Células Th1/citologia , Diferenciação Celular/imunologia , Polaridade Celular , Colo/imunologia , Colo/patologia , Glicina Hidroximetiltransferase/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Ribonucleoproteínas/metabolismo , Células Th1/imunologia , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Modified citrus pectin (MCP) is a carbohydrate enriched complex, which has been implicated in cancer treatment and prevention. However, the effects of MCP on urinary bladder cancer (UBC) are unknown. In this study, MCP was first tested in T24 and J82 human UBC cells and showed the inhibition of cell viability by the sulforhodamine B (SRB) assay. The MCP-treated UBC cells exhibited G2/M phase arrest with the decrease of Cyclin B1 and phosphorylated Cdc2. Caspase-3 was also activated, leading to the cleavage of Caspase-3 and PARP. We further explored the possible molecular mechanisms upon MCP treatment in UBC cells. Reduction of galectin-3 was observed and followed with the inactivation of Akt signaling pathway. Of note, galectin-3 knockdown by RNA interference recapitulated the MCP-mediated anti-proliferation, cell cycle arrest and apoptosis. Moreover, oral administration of MCP to the T24 xenograft-bearing nude mice inhibited the tumor growth significantly (P < 0.05). Quantification analysis of immunohistochemistry staining for Ki67 and cleaved Caspase-3 confirmed the decrease of proliferation index (P < 0.05) and the increase of apoptosis index (P < 0.01) in 700 mg/kg MCP-fed UBC xenografts. Using the information from TCGA database, we revealed that the overexpression of galectin-3 was associated with high tumor grade with lymph node metastasis, poor overall survival in UBC patients. Considering the remarkable inhibitory effects of MCP on UBC cell proliferation and survival in vitro and in vivo mainly through galectin-3, which is upregulated in UBCs, MCP may become an attractive agent, as a natural dietary fiber, for prevention and therapy of UBCs.
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Antineoplásicos/uso terapêutico , Regulação para Baixo , Galectina 3/genética , Pectinas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas , Caspase 3/metabolismo , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Galectinas , Humanos , Masculino , Camundongos Nus , Pectinas/farmacologia , Neoplasias da Bexiga Urinária/genéticaRESUMO
Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.
RESUMO
Total flavonoids isolated from Radix Tetrastigmae (RTFs) possess immunomodulatory activity, particularly on inflammation. In mice with lipopolysaccharide (LPS)induced acute lung injury (ALI), treatment with RTFs at 40, 80 and 160 mg/kg significantly reduced leukocyte infiltration, improved histopathological changes in lung tissues and decreased the LPSinduced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colonystimulating factor, monocyte inflammatory protein1α and Blymphocyte colony inflammatory cytokines, including interleukin (IL)1ß, IL6, IL12p40 and tumor necrosis factorα, in a dosedependent manner. In addition, the expression of the Tolllike receptor 4 (TLR4)/myeloid differentiation factor2 (MD2) compound, the phosphorylation of p38 mitogenactivated protein kinase (p38MAPK), cJun Nterminal kinase (JNK) and nuclear transcription factorκB (NFκB), in addition to the DNA binding activity of NFκB p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signalregulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPSinduced ALI through the TLR4/MD-2-mediated NFκB, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.
Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Flavonoides/farmacologia , Lipopolissacarídeos/efeitos adversos , Antígeno 96 de Linfócito/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/biossíntese , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica , Mediadores da Inflamação/sangue , Contagem de Leucócitos , Antígeno 96 de Linfócito/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Fosforilação , Receptor 4 Toll-Like/genéticaRESUMO
OBJECTIVE: To observe the protective effect of active fractions of Huanglian Jiedu Decoction (HJD) on primary cortical neuron injury after oxygen-glucose deprivation (OGD)/reperfusion (R) injury. Methods Using macroporous resin method, HJDFE30, HJDFE50, HJDFE75, and HJDFE95 with 30%, 50%, 75%, and 95% alcohol were respectively prepared. Then the content of active components in different HJD fractions was determined with reverse phase high-performance liquid chromatography (RP-HPLC). The OGD/R injury model was induced by sodium dithionite on primary cortical neurons in neonate rats. MTT assay was used to observe the effect of four fractions (HJDFE30, HJDFE50, HJDFE75, and HJDFE95) and seven index components of HJD on the neuron viability. RESULTS: RP-HPLC showed active component(s) contained in HJDFE30 was geniposide; baicalin, palmatine, berberine, and wogonside contained in HJDFE50; baicalin, berberine, baicalein, and wogonin contained in HJDFE75. The neuron viability was decreased after OGD for 20 min and reperfusion for 1 h, (P <0. 01), and significantly increased after administered with HJD, HJDFE30, HJDFE50, and HJDFE75 (P <0. 05, P <0. 01). Geniposide, baicalin, baicalein, palmatine, wogonside, and wogonin could increase the cortical neuron viability (P <0. 05, P <0. 01). CONCLUSIONS: HJDFE30, HJDFE50, and HJDFE75, as active fractions of HJD, had protective effect on primary cortical neuron injury after OGD/R. Furthermore, geniposide, baicalin, and baicalein were main active components of HJD.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glucose/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Berberina , Alcaloides de Berberina , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas , Flavonoides , Iridoides , Modelos Animais , Neurônios , RatosRESUMO
OBJECTIVE: To study the effect of Tangshenkang Granule (TG) containing serum on renal mesangial cells' (RMCs) proliferation and TGF-ß1/Smad2/3 pathway in the high glucose condition. METHODS: Twelve SD rats were randomly divided into four groups, i.e., the low dose TG group, the middle dose TG group, the high dose TG group, and the blank control group, 3 in each group. After 7-day gastrogavage via portal vein blood, rats were sacrificed and their serum samples were collected. RMCs were cultured in common rat serum and TG containing serum respectively. The proliferation of mesangial cells was determined by methly thiazolyl tetrazolium (MTT) assay to determine the optimal TG containing serum concentration. Expression levels of TGF-ß1 mRNA and protein were determined by real time quantitative PCR and ELISA. Smad2/3 protein expression and phosphorylation were determined by Western blot and immunofluorescence. RESULTS: TG containing serum at different doses could inhibit high glucose induced RMC cells' proliferation, TGF-ß1 over-expression and Smad2/3 phosphorylation. CONCLUSION: TG containing serum could inhibit high glucose induced RMC cells' proliferation, and its mechanism might be possibly associated with inhibiting TGF-ß1/Smad2/3 signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Proliferação de Células , Glucose , Células Mesangiais , Fosforilação , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Soro , Transdução de Sinais , Proteína Smad2/metabolismoRESUMO
Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Crocus/química , Neoplasias Pulmonares/patologia , Extratos Vegetais/farmacologia , Animais , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Undisturbed sediment cores were collected from Meiliang Bay, Taihu Lake. Immobilized nitrogen cycling bacteria (INCB), Elodea nuttallii were added to four groups of restoration incubation chambers respectively to explore the nitrogen removal mechanism in different restoration treatments. uN tracer and isotope pairing technique were used to determine the rates of plant uptake and denitrification in different treatments. The results showed that denitrification rates were significantly different among the treatments, while cores with addition of both INCB and Elodea nuttallii achieved the highest denitrification rate of 99.35 µmol · (m2 · h)( -1) and plant uptake rate of 36.55 µg · (m2 · h) -1. Elodea nuttallii in the cores could assimilate nitrate itself and enhance coupled nitrification- denitrification. Compared with plant uptake, denitrification was the main pathway of nitrogen removal. The results also showed that the combination of Elodea nuttallii and INCB could promote benthic nitrogen removal and purification of water body.
Assuntos
Bactérias/metabolismo , Ciclo do Nitrogênio , Nitrogênio/análise , Plantas/metabolismo , Microbiologia da Água , China , Desnitrificação , Lagos/química , Lagos/microbiologia , Nitratos/análise , NitrificaçãoRESUMO
OBJECTIVE: To study effects of Chinese Herbal Compounds (CHC) for blood activating stasis removing (BASR), qi benefiting Shen invigorating (QBSI) on high glucose stimulated proliferation of renal mesangial cells (RMCs) and expressions of fibronectin (FN). METHODS: Rats' RMCs were dealt with high glucose and different concentrations of Chinese medicine for 24 and 48 h respectively. The proliferation of RMCs was detected with 4-A thiazolyl blue. mRNA expressions of FN was detected by real time quantitative PCR. The protein expression of FN was detected by ELISA. RESULTS: Compared with the control group, the proliferation obviously increased (P < 0.05, P < 0.01) after 24 and 48 h of treatment in the high glucose group, mRNA and protein expressions of FN also increased (P < 0.01). There was no statistical difference in the proliferation of RMCs or expressions of FN at 24 h between each CHC group and the high glucose group (P > 0.05). Compared with the high glucose group, the proliferation of RMCs and expressions of FN at 24 h each obviously decreased in the CHC group (P < 0.05, P < 0.01). CONCLUSIONS: High glucose could promote the proliferation of RMCs and induce expressions of FN. No obvious effect could be stimulated by CHC treatment for 24 h. The proliferation of RMCs, protein and mRNA expressions of FN could be reversed by CHC treatment for 48 h.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fibronectinas/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Animais , Células Cultivadas , Glucose/efeitos adversos , Túbulos Renais/citologia , Masculino , RNA Mensageiro/genética , RatosRESUMO
Traditional Chinese medicine (TCM) has been extensively applied as preferable herbal remedy for menopausal symptoms. In the present work, the potential of a TCM recipe named RRF, composed of Radix Astragali, Radix Angelicae Sinensis, and Folium Epimedii, was investigated on a natural aging rat model. After administration of RRF (141, 282, and 564 mg/kg/d), the circulated estradiol (E2) level increased accompanied by a reduction of serum follicle stimulating hormone (FSH). But no significant impact on serum lutenizing hormone (LH) level was observed. As a result of the E2-FSH-LH adjustment, the histomorphology degenerations of ovary, uterus, and vagina of the 11.5-month female rats were alleviated. And lumbar vertebrae trabecular microstructure was also restored under RRF exposure by means of increasing the trabecular area and area rate. Moreover, levels of hypothalamic dopamine (DA) and norepinephrine (NE) rallied significantly after RRF treatment. Results from our studies suggest that RRF possesses a positive regulation on the estrogen imbalance and neurotransmitter disorder, thereby restoring reproductive organ degeneration and skeleton deterioration. The above-mentioned benefits of RRF on the menopause syndromes recommend RRF as a potential candidate for the treatment of perimenopausal syndrome.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (Pae) is extracted from the root of paeonia lactiflora which have attracted attention for anti-rheumatic and immune modulating properties. AIM OF THE STUDY: To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen-induced arthritis (CIA). MATERIALS AND METHODS: CIA rats were randomly separated into different groups and treated with Pae (25, 100mg/kg) from day 18 to day 38 after immunization. The effects of Pae on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF-R, PI3K, p-Akt and mTOR. RESULTS: In CIA rats, the levels of anti-CII antibody, IgA, IgG and IgM in serum enhanced, BAFF, BAFF-R, PI3K, p-Akt and mTOR were highly expressed. Pae (100mg/kg) obviously decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology in CIA rats, decreased the levels of IgA, IgM, IgG and anti-CII antibody, and significantly decreased the expressions of BAFF, BAFF-R, PI3K, p-Akt and mTOR. CONCLUSION: PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats. Pae had therapeutic effects on rats with CIA. These effects might be relative to regulating PI3K/Akt/mTOR signal mediated by BAFF/BAFF-R, and down regulate the antibodies production further.
Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Autoanticorpos/sangue , Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/imunologia , Benzoatos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Glucosídeos/farmacologia , Paeonia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Articulação do Tornozelo/efeitos dos fármacos , Articulação do Tornozelo/enzimologia , Articulação do Tornozelo/imunologia , Articulação do Tornozelo/patologia , Anti-Inflamatórios/isolamento & purificação , Artrite Experimental/enzimologia , Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/enzimologia , Linfócitos B/imunologia , Benzoatos/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Glucosídeos/isolamento & purificação , Masculino , Monoterpenos , Paeonia/química , Fosforilação , Fitoterapia , Raízes de Plantas , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/enzimologia , Baço/imunologia , Baço/patologia , Fatores de TempoRESUMO
The products of the FIS genes play important regulatory roles in diverse developmental processes, especially in seed formation after fertilization. In this study, a FIS-class gene MhFIE was isolated from apple. It encoded a predicted protein highly similar to polycomb group (PcG) protein FERTILIZATION-INDEPENDENT ENDOSPERM (FIE). MhFIE functioned as an Arabidopsis FIE homologue, as indicated by functional complementation experiment using Arabidopsis fie mutant. In addition, BiFC assay showed that MhFIE protein interacted with AtCLF. Furthermore, transgenic Arabidopsis ectopically expressing MhFIE produced less APETALA3 (AtAP3) and AGAMOUS (AtAG) transcripts than WT control, and therefore exhibited abnormal flower, seed development. These results suggested that polycomb complex including FIE and CLF proteins played an important role in reproductive development by regulating the expression of its downstream genes. In addition, it was found that MhFIE constitutively expressed in various tissues tested. Its expression levels were lower in apomictic apple species than the sexual reproductive species, suggested it was possibly involved into apomixis in apple. Furthermore, the hybrids of tea crabapple generated MhFIE transcripts at different levels. The parthenogenesis capacity was negatively correlated with MhFIE expression level in these hybrids. These results suggested that MhFIE was involved into the regulation of flower development and apomixis in apple.