RESUMEN
Metabolic dysfunction-associated fatty liver disease is a metabolic disease caused by abnormal lipid accumulation in the liver. Excessive lipid accumulation results in liver inflammation and fibrosis. Previous studies have demonstrated that the chalcone licochalcone D, which is isolated from Glycyrrhiza inflata Batal, has anti-tumor and anti-inflammatory effects. The present study explored whether licochalcone D can regulate lipid accumulation in fatty liver cells. FL83B hepatocytes were incubated with oleic acid to establish a fatty liver cell model, and then treated with licochalcone D to evaluate the molecular mechanisms underlying the regulation of lipid metabolism. In addition, male C57BL/6 mice were fed a methionine/choline-deficient diet to induce an animal model of metabolic dysfunction-associated steatohepatitis (MASH) and given 5 mg/kg licochalcone D by intraperitoneal injection. In cell experiments, licochalcone D significantly reduced lipid accumulation in fatty liver cells and reduced sterol regulatory element-binding protein 1c expression, blocking fatty acid synthase production. Licochalcone D increased adipose triglyceride lipase and carnitine palmitoyltransferase 1 expression, enhancing lipolysis and fatty acid ß-oxidation, respectively. Licochalcone D also significantly increased SIRT-1 and AMPK phosphorylation, reducing acetyl-CoA carboxylase phosphorylation and inhibiting fatty acid synthesis. Licochalcone D also increased the fusion of autophagosomes and lysosomes to promote autophagy, reducing oil droplet accumulation in fatty liver cells. In the animal experiments, licochalcone D effectively reduced the number of lipid vacuoles and degree of fibrosis in liver tissue and inhibited liver inflammation. Thus, licochalcone D can improve MASH by reducing lipid accumulation, inhibiting inflammation, and increasing autophagy.
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Autofagia , Chalconas , Hepatocitos , Metabolismo de los Lípidos , Lipogénesis , Ratones Endogámicos C57BL , Animales , Autofagia/efectos de los fármacos , Chalconas/farmacología , Lipogénesis/efectos de los fármacos , Masculino , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Línea Celular , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Hígado Graso/patologíaRESUMEN
Punicalagin (PUN) was isolated from the peel of pomegranate (Punica granatum L.), is a polyphenol with anti-inflammatory, hepatoprotective, and antioxidant activities. However, it remains unclear whether PUN alleviates the inflammation and anti-inflammatory mechanisms in pro-inflammatory cytokines-induced human keratinocyte HaCaT cells. Here, we investigated that tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mixture-stimulated HaCaT cells were treated with various concentrations of PUN, followed by analyzed the expression of inflammation-related mediators and evaluate anti-inflammatory-related pathways. Our results demonstrated that PUN ≤ 100 µM did not reduce HaCaT cell viability, and PUN ≥ 3 µM was sufficient to decrease interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 5 (CCL5), CCL17 and CCL20 concentrations. We found that PUN ≥ 10 µM and ≥ 3 µM significantly increased sirtuin 1 (SIRT1) expression and inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. PUN downregulated inflammation-related proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), enhanced nuclear factor erythroid-2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, PUN decreased intercellular adhesion molecule-1 (ICAM-1) expression and inhibited monocyte adhesion to inflamed HaCaT cells. PUN also suppressed inflammatory-related pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in TNF-α/IFN-γ- stimulated HaCat cells. Collectively, there is significant evidence that PUN has effective protective defenses against TNF-α/IFN-γ-induced skin inflammation by enhancing SIRT1 to mediate STAT3 and Nrf2/HO-1 signaling pathway.
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Taninos Hidrolizables , Granada (Fruta) , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Sirtuina 1/metabolismo , Interferón gamma/metabolismo , Granada (Fruta)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Hemo-Oxigenasa 1/metabolismo , Células HaCaT , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , FN-kappa B/metabolismo , Antiinflamatorios/uso terapéutico , Inflamación/metabolismoRESUMEN
Myricetin, a flavonoid isolated from many edible vegetables and fruits, has multiple biological effects, including anti-inflammatory and anti-tumor effects. Myricetin could inhibit mast cell degranulation in vitro, and it reduced the eosinophil content in bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-sensitized mice. However, it remains unclear whether myricetin alleviates airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthma. Here, we investigated whether myricetin attenuated AHR, airway inflammation, and eosinophil infiltration in lungs of asthmatic mice. Mice were sensitized with OVA, then injected intraperitoneally with myricetin to investigate anti-inflammatory and antioxidant effects of myricetin. Moreover, we examined its effects on human bronchial epithelial BEAS-2B cells stimulated with TNF-α and IL-4, in vitro. Myricetin effectively mitigated eosinophil infiltration, AHR, and goblet cell hyperplasia in lung, and it reduced Th2 cytokine expression in BALF from asthmatic mice. Myricetin effectively promoted glutathione and superoxide dismutase productions and mitigated malondialdehyde expressions in mice by promoting Nrf2/HO-1 expression. Myricetin also reduced the production of proinflammatory cytokines, eotaxins, and reactive oxygen species in BEAS-2B cells. Myricetin effectively suppressed ICAM-1 expression in inflammatory BEAS-2B cells, which suppressed monocyte cell adherence. These results suggested that myricetin could effectively improve asthma symptoms, mainly through blocking Th2-cell activation, which reduced oxidative stress, AHR, and airway inflammation.
Asunto(s)
Asma , Humanos , Animales , Ratones , Ovalbúmina/toxicidad , Asma/inducido químicamente , Asma/tratamiento farmacológico , Asma/patología , Pulmón , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/metabolismo , Citocinas/metabolismo , Inflamación/metabolismo , Líquido del Lavado Bronquioalveolar , Estrés Oxidativo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
Mulberroside F is isolated from the leaves and roots of Morus alba L. Here, we investigated whether mulberroside F could alleviate airway inflammation and eosinophil infiltration in the lungs of asthmatic mice. We also examined whether mulberroside F attenuated inflammatory responses in human tracheal epithelial BEAS-2B cells. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and administered different doses of mulberroside F via intraperitoneal injection. Additionally, tumor necrosis factor (TNF)-α-stimulated BEAS-2B cells were treated with various doses of mulberroside F, followed by detection of the expressions of inflammatory cytokines and chemokines. The results demonstrated that mulberroside F mitigated the levels of proinflammatory cytokines and chemokines, and CCL11, in inflammatory BEAS-2B cells. Mulberroside F also suppressed reactive oxygen species (ROS) production and ICAM-1 expression in TNF-α-stimulated BEAS-2B cells, which effectively suppressed monocyte cell adherence. In an animal model of asthma, mulberroside F treatment attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia. Mulberroside F treatment also decreased lung fibrosis and airway inflammation in OVA-sensitized mice. Moreover, mulberroside F significantly reduced expressions of Th2-associated cytokines (including interleukin(IL)-4, IL-5, and IL-13) in bronchoalveolar lavage fluid compared to OVA-sensitized mice. Our results confirmed that mulberroside F is a novel bioactive compound that can effectively reduce airway inflammation and eosinophil infiltration in asthmatic mice via inhibition of Th2-cell activation.
Asunto(s)
Asma , Hipersensibilidad Respiratoria , Femenino , Humanos , Animales , Ratones , Ovalbúmina/metabolismo , Ovalbúmina/farmacología , Ovalbúmina/uso terapéutico , Asma/tratamiento farmacológico , Asma/metabolismo , Pulmón/patología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/patología , Citocinas/metabolismo , Quimiocinas/metabolismo , Inflamación/patología , Factor de Necrosis Tumoral alfa/metabolismo , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Olive (Olea europaea Linn) leaves contain a phenolic compound oleuropein (Ole) has antioxidant, anti-inflammatory, and immunomodulatory activities. However, whether Ole might be an effective treatment for atopic dermatitis (AD) remains unknown. OBJECTIVE: This study investigated the functional role of oleuropein in a 2,4-dinitrochlorobenzene-induced AD-like mouse model, with a focus on allergic inflammation. METHODS: We evaluated cytokine gene expression, COX-2 inflammatory protein production, and Th2 related cytokine regulation of mast cells and eosinophils that infiltrated AD-like skin lesions. RESULTS: A topical application of Ole significantly reduced Th2-related cytokine gene expression (IL-4 and IL-5) and inflammatory COX-2 protein production in AD-like skin lesions. Additionally, Ole suppressed serum IgE levels. Furthermore, Ole effectively reduced ear swelling and epidermal and dermal thickening. CONCLUSIONS: These results suggested that, mechanistically, Ole treatment improved allergic inflammation by blocking the Th2-driven inflammatory axis. In conclusion, our findings indicated that Ole showed promise in treating AD by regulating serum IgE and Th2 cytokine levels. Although the effects of Ole on AD in humans require clinical trials, our results provided insights into how AD treatments might be improved.
RESUMEN
Our previous study found that oral administration of Gynostemma pentaphyllum extract can attenuate airway hyperresponsiveness (AHR) and reduce eosinophil infiltration in the lungs of asthmatic mice. Gypenoside A is isolated from G. pentaphyllum. In this study, we investigated whether gypenoside A can effectively reduce asthma in mice. Asthma was induced in BALB/c mice by ovalbumin injection. Asthmatic mice were treated with gypenoside A via intraperitoneal injection to assess airway inflammation, AHR, and immunomodulatory effects. In vitro, gypenoside A reduced inflammatory and oxidative responses in inflammatory tracheal epithelial cells. Experimental results showed that gypenoside A treatment can suppress eosinophil infiltration in the lungs, reduce tracheal goblet cell hyperplasia, and attenuate AHR. Gypenoside A significantly reduced Th2 cytokine expression and also inhibited the expression of inflammatory genes and proteins in the lung and bronchoalveolar lavage fluid. In addition, gypenoside A also significantly inhibited the secretion of inflammatory cytokines and chemokines and reduced oxidative expression in inflammatory tracheal epithelial cells. The experimental results suggested that gypenoside A is a natural compound that can effectively reduce airway inflammation and AHR in asthma, mainly by reducing Th2 cell activation.
Asunto(s)
Asma , Células Th2 , Animales , Asma/tratamiento farmacológico , Asma/metabolismo , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Eosinófilos/metabolismo , Gynostemma , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Pulmón/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/metabolismo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Células Th2/metabolismoRESUMEN
Fisetin is isolated from many fruits and vegetables and has been confirmed to improve airway hyperresponsiveness in asthmatic mice. However, whether fisetin reduces inflammatory response and oxidative stress in bronchial epithelial cells is unclear. Here, BEAS-2B human bronchial epithelial cells were treated with various concentrations of fisetin and then stimulated with tumor necrosis factor-α (TNF-α) or TNF-α/interleukin-4. In addition, ovalbumin-sensitized mice were treated with fisetin to detect inflammatory mediators and oxidative stress expression. Fisetin significantly reduced the levels of inflammatory cytokines and chemokines in TNF-α-stimulated BEAS-2B cells. Fisetin also attenuated intercellular adhesion molecule-1 expression in TNF-α-stimulated BEAS-2B cells, suppressing THP-1 monocyte adhesion. Furthermore, fisetin significantly suppressed airway hyperresponsiveness in the lungs and decreased eosinophil numbers in the bronchoalveolar lavage fluid of asthmatic mice. Fisetin decreased cyclooxygenase-2 expression, promoted glutathione levels, and decreased malondialdehyde levels in the lungs of asthmatic mice. Our findings indicate that fisetin is a potential immunomodulator that can improve the pathological features of asthma by decreasing oxidative stress and inflammation.
Asunto(s)
Asma , Hipersensibilidad Respiratoria , Animales , Asma/patología , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Células Epiteliales/metabolismo , Flavonoles , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/metabolismo , Estrés Oxidativo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation in visceral adipocyte tissue. Here we investigated whether acacetin regulated the mechanisms of lipogenesis and inflammation in non-alcoholic fatty liver disease (NAFLD) in obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), and then administered acacetin by intraperitoneal injection. Acacetin reduced body weight and liver weight in obese mice. Acacetin-treated obese mice exhibited decreased lipid accumulation, increased glycogen accumulation, and improved hepatocyte steatosis. Acacetin regulated triglycerides and total cholesterol in the liver and serum. Acacetin decreased low-density lipoprotein and leptin concentrations, but increased high-density lipoprotein and adiponectin levels in obese mice. Acacetin effectively weakened the gene expressions of transcription factors related to lipogenesis, and promoted the expressions of genes related to lipolysis and fatty acid ß-oxidation in liver. Acacetin also reduced expressions of inflammation-related cytokines in the serum and liver. Oleic acid induced lipid accumulation in murine FL83B hepatocytes, and the effects of acacetin treatment indicated that acacetin may regulate lipid metabolism through the AMPK pathway. Acacetin may protect against hepatic steatosis by modulating inflammation and AMPK expression.
Asunto(s)
Flavonas , Enfermedad del Hígado Graso no Alcohólico , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Flavonas/farmacología , Flavonas/uso terapéutico , Inflamación/metabolismo , Metabolismo de los Lípidos , Lipogénesis/genética , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Triglicéridos/metabolismoRESUMEN
Urolithin A is an active compound of gut-microbiota-derived metabolites of polyphenol ellagic acid that has anti-aging, antioxidative, and anti-inflammatory effects. However, the effects of urolithin A on polyinosinic acid-polycytidylic acid (poly(I:C))-induced inflammation remain unclear. Poly(I:C) is a double-stranded RNA (dsRNA) similar to a virus and is recognized by Toll-like receptor-3 (TLR3), inducing an inflammatory response in immune cells, such as macrophages. Inflammation is a natural defense process of the innate immune system. Therefore, we used poly(I:C)-induced RAW264.7 cells and attenuated the inflammation induced by urolithin A. First, our data suggested that 1-30 µM urolithin A does not reduce RAW264.7 cell viability, whereas 1 µM urolithin A is sufficient for antioxidation and the decreased production of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and C-C chemokine ligand 5. The inflammation-related proteins cyclooxygenase-2 and inducible nitric oxide synthase were also downregulated by urolithin A. Next, 1 µM urolithin A inhibited the levels of interferon (INF)-α and INF-ß. Urolithin A was applied to investigate the blockade of the TLR3 signaling pathway in poly(I:C)-induced RAW264.7 cells. Moreover, the TLR3 signaling pathway, subsequent inflammatory-related pathways, and antioxidation pathways showed changes in nuclear factor-κB (NF-κB) signaling and blocked ERK/mitogen-activated protein kinase (MAPK) signaling. Urolithin A enhanced catalase (CAT) and superoxide dismutase (SOD) activities, but decreased malondialdehyde (MDA) levels in poly(I:C)-induced RAW264.7 cells. Thus, our results suggest that urolithin A inhibits TLR3-activated inflammatory and oxidative-associated pathways in macrophages, and that this inhibition is induced by poly(I:C). Therefore, urolithin A may have antiviral effects and could be used to treat viral-infection-related diseases.
Asunto(s)
Cumarinas , FN-kappa B , Receptor Toll-Like 3 , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Animales , Antioxidantes/farmacología , Cumarinas/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Ratones , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Poli I-C/farmacología , Células RAW 264.7 , ARN Bicatenario/farmacología , Factor de Transcripción STAT1/antagonistas & inhibidores , Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Receptor Toll-Like 3/antagonistas & inhibidores , Receptor Toll-Like 3/metabolismoRESUMEN
CONTEXT: Astragaloside IV isolated from Astragalus membranaceus (Fisch.), which was reported to have anti-tumor, anti-asthma, and suppressed cigarette smoke-induced lung inflammation in mice. OBJECTIVES: This study investigated whether astragaloside IV reduced the expression of inflammatory mediators and oxidative stress in BEAS-2B cells. METHODS: BEAS-2B cells treated with astragaloside IV, and then stimulated with TNF-α or TNF-α/IL-4. The levels of cytokine and chemokine were analysed with ELISA and real-time PCR. RESULTS: Astragaloside IV significantly inhibited the levels of CCL5, MCP-1, IL-6 and IL-8. Astragaloside IV also reduced ICAM-1 expression for blocked THP-1 monocyte adhesion to BEAS-2B cells. Furthermore, astragaloside IV attenuated the phosphorylation of MAPK, and reduced the translocation of p65 into the nucleus. Astragaloside IV could increase the expression of HO-1 and Nrf2 for promoting the oxidant protective effect. CONCLUSION: Aastragaloside IV has an anti-inflammatory and oxidative effect via regulated NF-κB, MAPK and HO-1/Nrf2 signalling pathways in human bronchial epithelial cells.
Asunto(s)
Células Epiteliales , Sistema de Señalización de MAP Quinasas , FN-kappa B , Saponinas , Triterpenos , Línea Celular , Células Epiteliales/efectos de los fármacos , Humanos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , FN-kappa B/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Proinflammatory mediators such as interleukin (IL)-1ß cause retinal pigment epithelium (RPE) inflammation, which is related to visual deterioration, including age-related macular degeneration and diabetic retinopathy. Oleuropein is a polyphenol compound that shows potent anti-inflammatory, antioxidant, and anti-cancer activities, but its effects on IL-1ß-induced inflammation have not been examined in the adult RPE cell line ARPE-19. Here, we assessed the ability of oleuropein to attenuate this inflammation in ARPE-19 cells. IL-1ß induced secretion of the inflammatory cytokines IL-6, monocyte chemoattractant protein-1 (MCP)-1, and soluble intercellular adhesion molecule (sICAM)-1. As measured by enzyme-linked immunosorbent assay, oleuropein significantly inhibited levels of all three proteins and led to decreased monocyte adhesiveness to ARPE-19 cells. To clarify the underlying anti-inflammatory mechanisms, we used western blots to evaluate the effect of oleuropein on inactivation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results showed that oleuropein significantly decreased levels of the inflammatory mediator cyclooxygenase-2 and increased anti-inflammatory protein HO-1 expression. We next examined if the anti-inflammatory activity of oleuropein arises via inactivated NF-κB. We found that suppressing phosphorylation of the JNK1/2 and p38 MAPK signaling pathways inhibited IL-6, MCP-1, and sICAM-1 secretion, implicating these pathways and NF-κB suppression in the effects of oleuropein. These results indicate that oleuropein shows potential for the prevention and treatment of inflammatory diseases of the retina.
Asunto(s)
Antiinflamatorios/farmacología , Células Epiteliales/efectos de los fármacos , Glucósidos Iridoides/farmacología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Retinitis/tratamiento farmacológico , Adulto , Antiinflamatorios/uso terapéutico , Biomarcadores/metabolismo , Línea Celular , Células Epiteliales/metabolismo , Humanos , Interleucina-1beta , Glucósidos Iridoides/uso terapéutico , Epitelio Pigmentado de la Retina/metabolismo , Retinitis/inducido químicamente , Retinitis/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Tomatidine, which is isolated from green tomato, can ameliorate inflammation and oxidative stress in cells and animal experiments and has been shown to improve airway inflammation in a murine model of asthma. Here, we investigated whether tomatidine can ameliorate acute lung injury in mice. Mice were given tomatidine by intraperitoneal injection for 7 consecutive days, and then, lung injury was induced via intratracheal instillation of lipopolysaccharide (LPS). Tomatidine reduced inflammatory cytokine expressions in bronchoalveolar lavage fluid (BALF), attenuated neutrophil infiltration in the BALF and lung tissue, increased superoxide dismutase activity and glutathione levels, and alleviated myeloperoxidase expression in the lung tissue of mice with lung injury. Tomatidine also decreased inflammatory cytokine and chemokine gene expression in inflammatory lungs and attenuated the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B. Furthermore, tomatidine enhanced the production of heme oxygenase-1, decreased the secretion of inflammatory cytokines and chemokines in LPS-stimulated lung epithelial cells, and attenuated THP-1 monocyte adhesion. Our findings suggest that tomatidine attenuates oxidative stress and inflammation, improving acute lung injury in mice.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Inflamación , Neumonía/tratamiento farmacológico , Tomatina/análogos & derivados , Células A549 , Animales , Líquido del Lavado Bronquioalveolar , Adhesión Celular , Quimiocinas/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Humanos , Lipopolisacáridos/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos BALB C , Subunidad p50 de NF-kappa B/metabolismo , Neutrófilos/metabolismo , Estrés Oxidativo , Peroxidasa/biosíntesis , Superóxido Dismutasa/metabolismo , Tomatina/farmacologíaRESUMEN
Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.
Asunto(s)
Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Hipersensibilidad Respiratoria/tratamiento farmacológico , Xantófilas , Animales , Línea Celular , Citocinas/metabolismo , Células Epiteliales , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Xantófilas/administración & dosificación , Xantófilas/farmacologíaRESUMEN
Tomatidine is isolated from the leaves and green fruits of some plants in the Solanaceae family, and has been reported to have anti-inflammatory and antitumor effects. Previous studies have found that tomatidine decreases hepatic lipid accumulation via regulation of vitamin D receptor and activation of AMP-activated protein kinase (AMPK) phosphorylation. However, whether tomatidine reduces weight gain and improves nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated how tomatidine ameliorates NAFLD in obese mice and evaluated the regulatory mechanism of lipogenesis in hepatocytes. Male C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity and NAFLD, and treated with tomatidine via intraperitoneal injection. In vitro, FL83B hepatocytes were incubated with oleic acid and treated with tomatidine to evaluate lipid metabolism. Our results demonstrate that tomatidine significantly decreases body weight and fat weight compared to HFD-fed mice. In addition, tomatidine decreased hepatic lipid accumulation and improved hepatocyte steatosis in HFD-induced obese mice. We also found that tomatidine significantly regulated serum total cholesterol, fasting blood glucose, low-density lipoprotein, and triglyceride levels, but the serum high-density lipoprotein and adiponectin concentrations were higher than in the HFD-fed obese mice. In vivo and in vitro, tomatidine significantly suppressed the expression of fatty acid synthase and transcription factors involved in lipogenesis, and increased the expression of adipose triglyceride lipase. Tomatidine promoted the sirtuin 1 (sirt1)/AMPK signaling pathway to increase lipolysis and ß-oxidation in fatty liver cells. These findings suggest that tomatidine potentially ameliorates obesity and acts against hepatic steatosis by regulating lipogenesis and the sirt1/AMPK pathway.
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Antiinflamatorios/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Tomatina/análogos & derivados , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/patología , Tomatina/uso terapéuticoRESUMEN
Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1ß-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1ß-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.
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Interleucina-1beta/farmacología , Luteolina/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Hemo-Oxigenasa 1/metabolismo , Humanos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células THP-1RESUMEN
BACKGROUND: Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. METHODS: HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. RESULTS: Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid ß-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. CONCLUSIONS: These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.
RESUMEN
Licochalcone A is a chalcone isolated from Glycyrrhiza uralensis. It showed anti-tumor and anti-inflammatory properties in mice with acute lung injuries and regulated lipid metabolism through the activation of AMP-activated protein kinase (AMPK) in hepatocytes. However, the effects of licochalcone A on reducing weight gain and improving nonalcoholic fatty liver disease (NAFLD) are unclear. Thus, the present study investigated whether licochalcone A ameliorated weight loss and lipid metabolism in the liver of high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed an HFD to induce obesity and NAFLD, and then were injected intraperitoneally with licochalcone A. In another experiment, a fatty liver cell model was established by incubating HepG2 hepatocytes with oleic acid and treating the cells with licochalcone A to evaluate lipid metabolism. Our results demonstrated that HFD-induced obese mice treated with licochalcone A had decreased body weight as well as inguinal and epididymal adipose tissue weights compared with HFD-treated mice. Licochalcone A also ameliorated hepatocyte steatosis and decreased liver tissue weight and lipid droplet accumulation in liver tissue. We also found that licochalcone A significantly regulated serum triglycerides, low-density lipoprotein, and free fatty acids, and decreased the fasting blood glucose value. Furthermore, in vivo and in vitro, licochalcone A significantly decreased expression of the transcription factor of lipogenesis and fatty acid synthase. Licochalcone A activated the sirt-1/AMPK pathway to reduce fatty acid chain synthesis and increased lipolysis and ß-oxidation in hepatocytes. Licochalcone A can potentially ameliorate obesity and NAFLD in mice via activation of the sirt1/AMPK pathway.
Asunto(s)
Chalconas/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Dieta Alta en Grasa , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Obesidad/inducido químicamente , Sirtuina 1/metabolismoRESUMEN
Spilanthol (SP) is a bioactive compound found in Spilanthes acmella, giving the flowers and leaves a spicy taste. Studies found that phyto-ingredients stored in spice plants act against obesity-related diseases. SP has antimicrobial, anti-inflammatory, and analgesic properties, but the effects on obesity are not yet known. We investigated the effects of SP in differentiated adipocytes (3T3-L1 cells) and mice fed a high-fat diet (HFD). SP significantly inhibited intracellular lipid accumulation and significantly reduced the expression of lipogenesis-related proteins, including acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FAS). In contrast, SP increased the expression of carnitine palmitoyltransferase (CPT)1 and AMP-activated protein kinase (AMPK) in adipocytes. However, SP suppressed the levels of cyclooxygenase-2 (COX-2), phospho-p38 (pp38), and phospho-JNK (cJun N-terminal kinase) (pJNK) in LPS (lipopolysaccharide)-stimulated murine pre-adipocytes. SP administered to HFD-induced obese mice via intraperitoneal injections twice a week for 10 weeks decreased body weight gain, visceral adipose tissue weight, and adipocyte size. SP inhibited lipogenic proteins FAS and ACC, and suppressed adipogenic transcription factors, enhancing lipolysis and AMPK protein expression in the liver. SP has anti-obesity effects, upregulating AMPK to attenuate lipogenic and adipogenic transcription factors.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Fármacos Antiobesidad/farmacología , Metabolismo de los Lípidos , Obesidad/tratamiento farmacológico , Alcamidas Poliinsaturadas/farmacología , Células 3T3-L1 , Adipocitos , Adipogénesis/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Dieta Alta en Grasa , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Factores de Transcripción/metabolismoRESUMEN
Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.
Asunto(s)
Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Alcamidas Poliinsaturadas/uso terapéutico , Animales , Antialérgicos/administración & dosificación , Antialérgicos/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dermatitis Atópica/etiología , Dermatitis Atópica/metabolismo , Dinitroclorobenceno/toxicidad , Femenino , Inmunoglobulinas/genética , Inmunoglobulinas/metabolismo , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Alcamidas Poliinsaturadas/administración & dosificación , Alcamidas Poliinsaturadas/farmacologíaRESUMEN
A compound isolated from Glycyrrhizauralensis, licochalcone A (LA) exhibits anti-inflammatory and anti-tumor properties in various cell lines. LA has been found to promote autophagy and suppress specificity protein 1, inducing apoptosis in breast cancer cells. However, the regulation of breast cancer cell invasion and migration by LA is elusive. Thus, the present study investigated whether LA induces apoptosis and cellular motility in MDA-MB-231 breast cells, and investigated the underlying molecular mechanisms. MDA-MB-231 cells treated with LA and cell viability measured by cell counting kit-8 assay. Apoptotic signal proteins checked by flow cytometry, fluorescent staining, and Western blot. LA effectively suppressed cell migration, and modulated E-cadherin and vimentin expression by blocking MAPK and AKT signaling. LA inhibited cell proliferation and cell cycle, modulated mitochondrial membrane potential and DNA damage, and reduced oxidative stress in MDA-MB-231 cells. LA also activated cleaved-caspase 3 and 9, significantly decreased Bcl-2 expression, ultimately causing the release of cytochrome c from the mitochondria into the cytoplasm. Overall, our findings suggest that LA decreases cell proliferation and increases reactive oxygen species production for induced apoptosis, and regulates E-cadherin and vimentin by reducing MAPK and AKT signaling, resulting in suppressed MDA-MB-231 cell migration and invasion.