RESUMEN
A plant factory is a closed cultivation system that provides a consistent and modified environment for plant growth. We speculated that treatment of kale (Brassica oleracea) grown in a plant factory with NaCl, Na2SeO3, or both would increase the bioactive phytochemical levels including glucosinolates (GLSs) and isothiocyanates (ITCs), the key molecules in cancer prevention. The kale was harvested and analysed after treatment with NaCl and Na2SeO3 alone or in combination for 1 or 2 weeks. Exposure to NaCl alone but not Na2SeO3 increased plant root growth. Levels of sinigrin were increased by a 2-week exposure to Na2SeO3 alone or in combination with NaCl, whereas no changes were observed in glucoraphanin and gluconasturtiin gluconasturtiin levels. Importantly, the ITC concentration was affected by 2-week treatment with both compounds. To evaluate the bioactivity of kale, HepG2 human hepatoma cells were treated with plant extract for 6 h. Only the extract of kale roots exposed to a combination NaCl and Na2SeO3 for 2 weeks showed an increased expression of nuclear factor erythroid 2-related factor (Nrf2), which regulates genes encoding antioxidant proteins. These data suggest that co-treatment with NaCl and Na2SeO3 increased the ITC content and chemopreventive effects of kale root.
Asunto(s)
Brassica , Isotiocianatos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Raíces de Plantas/efectos de los fármacos , Óxidos de Selenio/metabolismo , Transducción de Señal , Cloruro de Sodio/farmacología , Cromatografía Líquida de Alta Presión , Glicósido Hidrolasas/metabolismo , Células Hep G2 , Humanos , Raíces de Plantas/enzimología , Raíces de Plantas/crecimiento & desarrolloRESUMEN
OBJECTIVES: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells. METHODS: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically. KEY FINDINGS: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells. CONCLUSION: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.
Asunto(s)
Antiinflamatorios/farmacología , Quimiocinas/metabolismo , Dermatitis Atópica/prevención & control , Queratinocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Rhamnaceae/química , Piel/efectos de los fármacos , Ácido Vanílico/análogos & derivados , Ácido Vanílico/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Quimiocina CCL17/metabolismo , Quimiocina CCL22/metabolismo , Quimiocinas/sangre , Quimiocinas/inmunología , Dermatitis Atópica/sangre , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/inmunología , Dinitroclorobenceno , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Interferón gamma/farmacología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Transducción de Señal/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Piel/patología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/metabolismo , Balance Th1 - Th2/efectos de los fármacos , Células Th2/efectos de los fármacos , Células Th2/inmunología , Células Th2/metabolismo , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Ácido Vanílico/aislamiento & purificaciónRESUMEN
The aim of our study is to investigate the molecular mechanism of gomisin J from Schisandra chinensis on the oleic acid (OA)-induced lipid accumulation in HepG2 cells. Gomisin J attenuated lipid accumulation in OA-induced HepG2 cells. It also suppressed the expression of lipogenic enzymes and inflammatory mediators and increased the expression of lipolytic enzymes in OA-induced HepG2 cells. Furthermore, the use of specific inhibitors and fetuin-A siRNA and liver kinase B1 (LKB1) siRNA transfected cells demonstrated that gomisin J regulated lipogenesis and lipolysis via inhibition of fetuin-A and activation of an AMP-activated protein kinase (AMPK)-dependent pathway in HepG2 cells. Our results showed that gomisin J suppressed lipid accumulation by regulating the expression of lipogenic and lipolytic enzymes and inflammatory molecules through activation of AMPK, LKB1, and Ca(2+)/calmodulin-dependent protein kinase II and inhibition of fetuin-A in HepG2 cells. This suggested that gomisin J has potential benefits in treating nonalcoholic fatty liver disease.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Lignanos/farmacología , Lipogénesis/efectos de los fármacos , Hígado/efectos de los fármacos , Ácido Oléico/metabolismo , Extractos Vegetales/farmacología , Compuestos Policíclicos/farmacología , Schisandra/química , alfa-2-Glicoproteína-HS/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Hígado/enzimología , Hígado/metabolismo , Transducción de Señal/efectos de los fármacos , alfa-2-Glicoproteína-HS/genéticaRESUMEN
Cassia tora seed is widely used due to its various biological properties including anticancer, antidiabetic, and anti-inflammatory effects. However, there has been no report of the effects of C. tora seed extract (CTE) on immunoglobulin E (IgE)-mediated allergic responses. In this research, we demonstrated the effects of CTE and its active compound aurantio-obtusin on IgE-sensitized allergic reactions in mast cells and passive cutaneous anaphylaxis (PCA). CTE and aurantio-obtusin suppressed degranulation, histamine production, and reactive oxygen species generation and inhibited the production and mRNA expression of tumor necrosis factor-α and interleukin-4. CTE and aurantio-obtusin also suppressed the prostaglandin E2 production and expression of cyclooxygenase 2. Furthermore, CTE and aurantio-obtusin suppressed IgE-mediated FcεRI signaling such as phosphorylation of Syk, protein kinase Cµ, phospholipase Cγ, and extracellular signal-regulated kinases. CTE and aurantio-obtusin blocked mast cell-dependent PCA in IgE-mediated mice. These results suggest that CTE and aurantio-obtusin are a beneficial treatment for allergy-related diseases.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Antraquinonas/administración & dosificación , Antialérgicos/administración & dosificación , Cassia/química , Inmunoglobulina E/inmunología , Mastocitos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Anafilaxia/inmunología , Animales , Humanos , Masculino , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Anafilaxis Cutánea Pasiva , Semillas/químicaRESUMEN
This study investigated the effects of youngiaside A (YA), youngiaside C (YC), and Youngia denticulatum extract (YDE) on extrinsic aging and assessed its molecular mechanisms in UVB-irradiated HaCaT keratinocytes and human dermal fibroblasts (HDFs). The results showed that YA, YC, and YDE decreased matrix metalloproteinase (MMP) expression and production in HaCaT cell and HDFs and increased collagen expression and production in HDFs. In addition, YA, YC, and YDE significantly increased antioxidant enzyme expression, thereby down-regulating UVB-induced reactive oxygen species (ROS) production and ROS-induced mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) signaling in HaCaT cells. Furthermore, YA, YC, and YDE reduced phosphorylation of IκBα and IKKα/ß, blocked nuclear factor-κB (NF-κB) p65 nuclear translocation, and strongly suppressed pro-inflammatory mediators. Finally, YA, YC, and YDE augmented UVB-induced adenosine monophosphate activated protein kinase (AMPK) phosphorylation and YA and YC did not inhibit MMP-1 production in AMPK inhibitor or nuclear factor-erythroid 2-related factor-2 (Nrf2) siRNA-treated HaCaT cells. The results suggest that these compounds could be potential therapeutic agents for prevention and treatment of skin photoaging.
Asunto(s)
Asteraceae/química , Fibroblastos/efectos de los fármacos , Metaloproteinasas de la Matriz/genética , Extractos Vegetales/farmacología , Procolágeno/biosíntesis , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Protectores Solares/farmacología , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Células Cultivadas , Colágeno Tipo I/biosíntesis , Fibroblastos/enzimología , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Humanos , Metaloproteinasas de la Matriz/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Transducción de Señal/efectos de la radiación , Piel/enzimología , Piel/metabolismo , Piel/efectos de la radiación , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Rayos UltravioletaRESUMEN
Hovenia dulcis Thunb. (Rhamnaceae) is a hardy tree native to Europe, the Middle East, and North Africa, and it is also grown in parts of Asia and has been used in traditional medicine to treat liver toxicity, stomach disorders, and inflammation. This study investigated the anti-allergy potential of an extract of the branches of H. dulcis (HDB) using the antigen-stimulated mast cell-like cell line rat basophilic leukemia (RBL)-2H3 and a passive cutaneous anaphylaxis (PCA) mouse model. Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses, and PCA were performed to measure allergic responses and proinflammatory mediators in antigen-stimulated rat basophilic leukemia (RBL)-2H3 mast cells and the PCA mouse model. In antigen-stimulated RBL-2H3 cells, HDB inhibited the secretion of ß-hexosaminidase (indicating the inhibition of degranulation) and histamine release; decreased expression and production of the inflammatory mediators, cyclooxygenase-2 and prostaglandin E2, and cytokines interleukin-4 and tumor necrosis factor-α; and suppressed activation of nuclear factor κB, a transcription factor involved in the response to cytokines. HDB attenuated phosphorylation of the mast cell downstream effectors Lyn, Syk, phospholipase Cγ, protein kinase Cµ, extracellular signal-regulated kinase and p38. In IgE-sensitized mice, HDB inhibited mast cell-dependent PCA. Furthermore, HDB contained pinosylvin and possessed significant anti-allergic activities. These results suggest that HDB would be of value in the prevention and treatment of allergic diseases.
Asunto(s)
Inmunoglobulina E/inmunología , Mastocitos/inmunología , Anafilaxis Cutánea Pasiva/inmunología , Rhamnaceae/química , Estilbenos/farmacología , Animales , Antialérgicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/genética , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipersensibilidad/tratamiento farmacológico , Interleucina-4/genética , Interleucina-4/metabolismo , Mastocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Ratas , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia anomala L. is used in Mongolian traditional medicine to treat various diseases including indigestion, abdominal pain, kidney disorders, inflammation, and female diseases. In this study we examined the effects of Paeonia anomala extract (PAE) and compounds derived from Paeonia anomala on immunoglobulin E (IgE)-mediated type I hypersensitivity responses in vitro. MATERIALS AND METHODS: Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses were performed to measure allergic and proinflammatory mediators in IgE-stimulated rat basophilic leukemia (RBL)-2H3 mast cells treated with or without PAE or gnetin H. RESULTS: Seventeen compounds were isolated, and ß-hexosaminidase release from IgE-stimulated RBL-2H3 mast cells was measured. Of the seventeen isolated compounds, gnetin H, a resveratrol derivative, significantly inhibited ß-hexosaminidase release from RBL-2H3 cells with an IC50 value of 0.3 µM. Notably, Gnetin H reduced ß-hexosaminidase release at lower concentrations than resveratrol. Furthermore, PAE and gnetin H inhibited histamine secretion, decreased the production and mRNA expression of tumor necrosis factor-α and interleukin-4 and suppressed translocation of nuclear factor κB. PAE and gnetin H also reduced the expression of cyclooxygenase-2 and production of prostaglandin E2. PAE and gnetin H suppressed the phosphorylation of Syk, protein kinase C (PKC)µ, phospholipase Cγ, and the mitogen-activated protein kinases, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. CONCLUSIONS: These results suggest that PAE and its active compound gnetin H could be promising therapeutic agents for allergic disorders.
Asunto(s)
Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Paeonia/química , Receptores de IgE/antagonistas & inhibidores , Resorcinoles/farmacología , Transducción de Señal/efectos de los fármacos , Estilbenos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Ratas , Receptores de IgE/metabolismo , Resorcinoles/química , Resorcinoles/aislamiento & purificación , Estilbenos/química , Estilbenos/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
Aceriphyllum rossii contains an abundant source of natural flavonoids with potential antioxidant, anticancer and anti-inflammatory properties. However, the effect of A. rossii extract (ARE) on immunoglobulin E(IgE)-mediated allergic responses remains unknown. In the present study, the effects of ARE and its active compounds, quercetin and kaempferol, on IgE-mediated rat basophilic leukemia mast cell activation and passive cutaneous anaphylaxis (PCA) were investigated. ARE, quercetin, and kaempferol inhibited secretion of ß-hexosaminidase and histamine, and reduced the production and mRNA expression of interleukin-4 and tumor necrosis factor-α. ARE also decreased the production of prostaglandin E2 and leukotriene B4 and expression of cyclooxygenase 2 and 5-lipoxygenase. Furthermore, ARE, quercetin, and kaempferol inhibited IgE-mediated phosphorylation of Syk, phospholipase Cγ, protein kinase C (PKC)µ, and the mitogen-activated protein kinases, extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. ARE, quercetin, and kaempferol markedly suppressed mast cell-dependent PCA in IgE-sensitized mice. These results indicate that ARE and its active constituents, quercetin and kaempferol, may be a useful therapy for immediate-type hypersensitivity.