RESUMO
People often experience cognitive deterioration of various degrees, from early-stage mild cognitive impairment to severe cognitive decline. Cognitive deterioration is related to many diseases and studied to alleviated inflammation reaction or oxidative stress. In the present study, the levels of various memory-related proteins: brain-derived neurotrophic factor (BDNF), amyloid beta (Aß) 42, Aß40, interleukin-6 and tumor necrosis factor-alpha were measured. Among Lactobacillus paracasei HP7 (HP7), Portulaca oleracea Linn. (PO) and HP7 together with PO (HP7A), the HP7A group had the best effect on increasing BDNF expression and suppressing Aß40 expression. Also, we measured the protective effect on scopolamine-induced cognitive decline in mice. In the acquisition test, the HP7A group most reliably relieved cognitive decline from days 2 to 5 of scopolamine injection. When the probe test was performed on the day 6 of scopolamine injection, the HP7A group had the shortest escape latency. Based on the results of the Morris water maze tasks, we suggest that HP7A is most useful for ameliorating cognitive decline. It is suggested that the HP7A ameliorating scopolamine-induced cognitive decline via the increase of BDNF expression and the suppression of Aß40 expression.
RESUMO
Gut dysbiosis is closely connected with the outbreak of psychiatric disorders with colitis. Bifidobacteria-fermented red ginseng (fRG) increases the absorption of ginsenoside Rd and protopanxatriol into the blood in volunteers and mice. fRG and Rd alleviates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Therefore, to understand the gut microbiota-mediated mechanism of fRG against anxiety/depression, we examined the effects of red ginseng (RG), fRG, ginsenoside Rd, and protopanaxatriol on the occurrence of anxiety/depression, colitis, and gut dysbiosis in mice. Mice with anxiety/depression were prepared by being exposed to two stressors, immobilization stress (IS) or Escherichia coli (EC). Treatment with RG and fRG significantly mitigated the stress-induced anxiety/depression-like behaviors in elevated plus maze, light-dark transition, forced swimming (FST), and tail suspension tasks (TST) and reduced corticosterone levels in the blood. Their treatments also suppressed the stress-induced NF-κB activation and NF-κB+/Iba1+ cell population in the hippocampus, while the brain-derived neurotrophic factor (BDNF) expression and BDNF+/NeuN+ cell population were increased. Furthermore, treatment with RG or fRG suppressed the stress-induced colitis: they suppressed myeloperoxidase activity, NF-κB activation, and NF-κB+/CD11c+ cell population in the colon. In particular, fRG suppressed the EC-induced depression-like behaviors in FST and TST and colitis more strongly than RG. fRG treatment also significantly alleviated the EC-induced NF-κB+/Iba1+ cell population and EC-suppressed BDNF+/NeuN+ cell population in the hippocampus more strongly than RG. RG and fRG alleviated EC-induced gut dysbiosis: they increased Bacteroidetes population and decreased Proteobacteria population. Rd and protopanaxatriol also alleviated EC-induced anxiety/depression and colitis. In conclusion, fRG and its constituents Rd and protopanaxatriol mitigated anxiety/depression and colitis by regulating NF-κB-mediated BDNF expression and gut dysbiosis.
Assuntos
Depressão , Alimentos Fermentados , Microbioma Gastrointestinal/efeitos dos fármacos , Ginsenosídeos/farmacologia , Sapogeninas/farmacologia , Animais , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Bifidobacterium/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Disbiose/metabolismo , Disbiose/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Panax/química , Panax/metabolismoRESUMO
Cacao beans from Theobroma cacao are an abundant source of polyphenols, particularly flavonoids. Previous studies demonstrated that cacao flavanols decrease pro-inflammatory cytokines resulting in the alleviation of allergic symptoms. We sought to investigate the effects of cacao extract (CE) on Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like symptoms. CE attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Histopathological analysis revealed that CE suppressed DFE-induced immune cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum immunoglobulin (Ig) E, chemokine; thymus and activation-regulated chemokine and macrophage-derived chemokine as well as the skin-derived cytokines interleukin (IL)-4, IL-5, and interferon-γ. CE also significantly alleviated transepidermal water loss and increased skin hydration. These results suggest that CE, a natural phytochemical-rich food, has potential therapeutic efficacy for the treatment of AD.
Assuntos
Cacau/química , Dermatite Atópica/tratamento farmacológico , Dermatophagoides farinae , Extratos Vegetais/farmacologia , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Dermatite Atópica/etiologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/tratamento farmacológico , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-4/sangue , Interleucina-4/imunologia , Interleucina-5/sangue , Interleucina-5/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos , Compostos Fitoquímicos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacosRESUMO
Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD.
Assuntos
Chlorella vulgaris/química , Dermatite Atópica/tratamento farmacológico , Dermatophagoides farinae/patogenicidade , Suplementos Nutricionais/microbiologia , Imunossupressores/administração & dosagem , Animais , Quimiocinas/sangue , Dermatite Atópica/imunologia , Dermatite Atópica/parasitologia , Modelos Animais de Doenças , Esquema de Medicação , Eosinófilos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Mastócitos/efeitos dos fármacos , CamundongosRESUMO
Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with a number of side effects, including hypertension. However, the presence of alternative bioactive compounds in licorice with anti-carcinogenic effects has long been suspected. Licochalcone A (LicoA) is a prominent member of the chalcone family and can be isolated from licorice root. To date, there have been no reported studies on the suppressive effect of LicoA against solar ultraviolet (sUV)-induced cyclooxygenase (COX)-2 expression and the potential molecular mechanisms involved. Here, we show that LicoA, a major chalcone compound of licorice, effectively inhibits sUV-induced COX-2 expression and prostaglandin E2 PGE2 generation through the inhibition of activator protein 1 AP-1 transcriptional activity, with an effect that is notably more potent than Gc. Western blotting analysis shows that LicoA suppresses sUV-induced phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinases (ERK)1/2/p90 ribosomal protein S6 kinase (RSK) in HaCaT cells. Moreover, LicoA directly suppresses the activity of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK)1, and B-Raf, but not Raf-1 in cell-free assays, indicating that PI3K, MEK1, and B-Raf are direct molecular targets of LicoA. We also found that LicoA binds to PI3K and B-Raf in an ATP-competitive manner, although LicoA does not appear to compete with ATP for binding with MEK1. Collectively, these results provide insight into the biological action of LicoA, which may have potential for development as a skin cancer chemopreventive agent.
Assuntos
Chalconas/farmacologia , Ciclo-Oxigenase 2/metabolismo , Glycyrrhiza/química , MAP Quinase Quinase 1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Ligação Competitiva/efeitos dos fármacos , Western Blotting , Células Cultivadas , Chalconas/química , Chalconas/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/biossíntese , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Ácido Glicirrízico/química , Ácido Glicirrízico/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , MAP Quinase Quinase 1/química , Modelos Moleculares , Estrutura Molecular , Fosfatidilinositol 3-Quinases/química , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Ligação Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas B-raf/química , Raios UltravioletaRESUMO
Atopic dermatitis (AD) is characterized by chronic highly pruritic and relapsing inflammatory skin lesions. Despite its growing prevalence, therapeutic treatments remain limited. Natural immune modulators from herbal extracts or derivatives may be useful for treating AD symptoms. This study examined the effect of 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF), a metabolite of soy isoflavone daidzin, on AD-like symptoms. Repeated epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) was performed on the ear and dorsal skin of NC/Nga mice to induce AD-like symptoms and skin lesions, and 7,8,4'-THIF (200 and 400 nmol) or tacrolimus (100 µg) was applied topically for 3 weeks to assess their anti-pruritic effects. We found that 7,8,4'-THIF alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness, and scratching behavior. Histopathological analysis demonstrated that 7,8,4'-THIF decreased DNCB-induced eosinophil and mast cell infiltration into skin lesions. We also found that 7,8,4'-THIF significantly alleviated DNCB-induced loss of water through the epidermal layer. In addition to reducing the DNCB-induced increase in serum IgE, 7,8,4'-THIF also lowered skin lesion levels of the chemokine thymus and activation regulated chemokine; Th2 cytokines interleukin (IL)-4, IL-5, and IL-13; and Th1 cytokines IL-12 and interferon-γ. These results suggest that 7,8,4'-THIF might be a potential therapeutic candidate for the treatment of atopic dermatitis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno , Isoflavonas/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Animais , Citocinas/análise , Citocinas/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Camundongos , Pele/imunologiaRESUMO
UNLABELLED: Cellular oxidative damage mediated by reactive oxygen species has been reported to inhibit gap-junctional intercellular communication (GJIC). In turn, the inhibition of GJIC can be attenuated by functional food compounds with antioxidant properties. In this study, we compared the protective effects of onion peel extract (OPE) and onion flesh extract (OFE) on oxidative stress-mediated GJIC inhibition, and investigated the mechanisms of action responsible. OPE restored H2 O2 -induced GJIC inhibition to a higher degree than OFE in WB-F344 rat liver epithelial cells. OPE was found to inhibit H2 O2 -induced phosphorylation of ERK1/2 and Cx43. A radical scavenging assay demonstrated superiority of OPE over OFE, suggesting that the observed effects might be mediated via an antioxidant mechanism. Quercetin is the major compound that is likely to be responsible for the protective effect against H2 O2 -mediated GJIC inhibition. This study suggests that OPE, a material often discarded, may be of value for the future development of functional food products. PRACTICAL APPLICATION: This study demonstrates that onion peel extract (OPE) exhibits a protective effect against the inhibition of gap-junctional intercellular communication (GJIC) mediated by H2 O2 , which is likely to occur via its antioxidant activity. OPE contains significant concentrations of bioactive phenolic compounds. Reductions in oxidative stress can lead to recovery of GJIC, which has been reported to be implicated in the prevention and treatment of cancers. These findings suggest that onion peel, a common waste product, could be used as potential resources for functional food development. Onion peel could be processed into a quercetin-rich powder or a pill for the prevention of cancer and other oxidative stress-related diseases.
Assuntos
Antioxidantes/farmacologia , Comunicação Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Cebolas/química , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Animais , Conexina 43/metabolismo , Células Epiteliais/metabolismo , Junções Comunicantes/metabolismo , Fígado/citologia , Fígado/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Oxirredução , Fosforilação/efeitos dos fármacos , Raízes de Plantas , Ratos , Ratos Endogâmicos F344RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng and ginsenosides are frequently used in the treatment of chronic inflammatory diseases. Recently, 20-O-ß-d-glucopyranosyl-20(S)-protopanaxadiol (GPD), the main metabolite of ginsenosides, was reported to have both anti-allergic and anti-pruritic effects. The immunomodulatory effects of GPD-fortified ginseng extract (GFGE) on atopic dermatitis (AD)-like symptoms in mice were investigated. This study was designed to investigate the preventive effect of GFGE on AD-like symptoms. MATERIALS AND METHODS: The effects of orally administered GFGE on Dermatophagoides farinae body extract (DFE)-induced AD-like symptoms in NC/Nga mice were assessed by analyzing dermatitis score, ear thickness, scratching time, skin histological changes, and serum level of macrophage-derived chemokine (MDC). In addition, splenocytes were isolated from the mice and stimulated with anti-CD3 and anti-CD28 monoclonal antibodies to produce cytokines. RESULTS: Oral administration of GFGE significantly attenuated DFE-induced increases in dermatitis score, ear thickness, scratching time, and severity of skin lesions in NC/Nga mice. GFGE treatment also reduced level of MDC in serum, infiltration of eosinophils and mast cells in skin, and production of cytokines in splenocytes. CONCLUSIONS: These results suggest that GFGE might ameliorate DFE-induced AD-like symptoms and be an alternative therapeutic agent for the prevention of AD.