RESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM), known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD) or to FL83B cells treated with free fatty acid (FFA). Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay. In mice, AM significantly reduced the body and liver weight, lipid accumulation in the liver, and levels of biochemical markers such as fatty acid synthase, hepatic triglyceride and leptin. Serum transaminases, indicators for hepatocyte injury, were also suppressed, while superoxide dismutase activity and liver antioxidant capacity were significantly increased. In FL83B cells, AM significantly reduced FFA-induced lipid droplet accumulation. Protein synthesis of an adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2) was inhibited in vivo. Furthermore, transcriptional activity of PPARγ2 was down-regulated in vitro, and mRNA expression of PPARγ2 and its downstream target genes, adipocyte protein 2 and lipoprotein lipase were down-regulated by AM both in vitro and in vivo. These results show beneficial effects of AM against hepatic lipid accumulation through the inhibition of PPARγ2 expression along with improvements in body weight, liver functions, lipid profiles and antioxidant capacity suggesting the potential therapeutic efficacy of AM on NAFLD.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , PPAR gamma/genética , Photinia/química , Extractos Vegetales/farmacología , Animales , Peso Corporal/efectos de los fármacos , Línea Celular , Dieta Alta en Grasa , Ácidos Grasos no Esterificados/farmacología , Leptina/análisis , Leptina/sangre , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , PPAR gamma/antagonistas & inhibidores , Photinia/metabolismo , Extractos Vegetales/química , Interferencia de ARN , Superóxido Dismutasa/metabolismo , Transaminasas/sangre , Triglicéridos/análisisRESUMEN
This study investigated the potential neuroprotective effect of a mushroom extract from Phellinus igniarius (Piwep) after transient cerebral ischemia. Ph. Igniarius, which has a history of traditional medicinal use, contains immunomodulatory compounds that have been described to have effects on the human immune system. Using a model of transient cerebral ischemia induced by both common carotid artery occlusion and hypovolemia, a water-ethanol extract precipitate of Ph. Igniarius (Piwep) was delivered intraperitoneally immediately after the insult and was injected subsequently every other day for the experimental course. Neuronal death was examined by Fluoro-Jade B staining 1 week after the insult. Piwep injection lead to decreased hippocampal neuronal death, suppression of oxidative injury, activation of microglia, and disruption of the blood-brain barrier. We conclude that Piwep potently inhibits hippocampal neuronal death following ischemia and may have a high therapeutic potential for ameliorating stroke-induced neuron death in the clinical setting.
Asunto(s)
Basidiomycota , Productos Biológicos/uso terapéutico , Hipocampo/efectos de los fármacos , Ataque Isquémico Transitorio/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Productos Biológicos/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Hipocampo/patología , Ataque Isquémico Transitorio/patología , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ratas , Accidente Cerebrovascular/patologíaRESUMEN
The present study aimed to evaluate the therapeutic potential of a mushroom extract from Phellinus igniarius in an animal model of multiple sclerosis. The medicinal mushroom, Phellinus igniarius, contains biologically active compounds that modulate the human immune system. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with myelin oligodendrocyte glycoprotein (MOG 35-55) in C57BL/6 female mice. A water-ethanol extract of Phellinus igniarius (Piwep) was delivered intraperitoneally every other day for the entire experimental course. Three weeks after the initial immunization, demyelination and immune cell infiltration in the spinal cord were examined. Piwep injection profoundly decreased the daily incidence rate and clinical score of EAE. The Piwep-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, macrophages, and B cells in the spinal cord. Piwep reduced expression of vascular cell adhesion molecule-1 (VCAM-1) in the spinal cord and integrin-α 4 in the lymph node of EAE mice. Piwep also inhibited proliferation of lymphocytes and secretion of interferon-γ in the lymph node of EAE mice. The results suggest that a mushroom extract, Piwep, may have a high therapeutic potential for ameliorating multiple sclerosis progression.
Asunto(s)
Agaricales/química , Productos Biológicos/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Linfocitos/patología , Médula Espinal/patología , Animales , Productos Biológicos/farmacología , Cerebelo/efectos de los fármacos , Cerebelo/patología , Progresión de la Enfermedad , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Integrina alfa4/genética , Integrina alfa4/metabolismo , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Linfocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito , ARN Mensajero/genética , ARN Mensajero/metabolismo , Médula Espinal/efectos de los fármacos , Molécula 1 de Adhesión Celular Vascular/metabolismo , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patologíaRESUMEN
Herbal medicine has been used in the orient for thousands of years to treat large and small ailments, including microbial infections. Although there are treatments for influenza virus infection, there is no treatment for drug-resistant viruses. It is time that we explored and exploited the multi-component nature of herbal extracts as multi-drug combination therapies. Here, we present data on the anti-influenza virus effect of a medicinal mushroom, Phellinus igniarius. The P. igniarius water extract was effective against influenza A and B viruses, including 2009 pandemic H1N1, human H3N2, avian H9N2, and oseltamivir-resistant H1N1 viruses. Virological assays revealed that the extract may interfere with one or more early events in the influenza virus replication cycle, including viral attachment to the target cell. Therefore, our results provide new insights into the use of P. igniarius as an anti-influenza medicine.
Asunto(s)
Antivirales/aislamiento & purificación , Basidiomycota/química , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza B/efectos de los fármacos , Humanos , Virus de la Influenza A/fisiología , Virus de la Influenza B/fisiología , Pruebas de Sensibilidad Microbiana , Orthomyxoviridae , Acoplamiento Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Cordyceps species have been known since long as a multi-utility ethnomedicinal herbal in Korea, China and Japan. It has been reported to exhibit a number of properties such as anti-oxidative, anti-cancer, antiinflammatory, anti-diabetic, and anti-obesity effects. In a previously conducted study, we had demonstrated that the ethanol extract of Cordyceps bassiana was able to suppress the production of interleukin (IL)-12 and interferon (IFN)-gamma in macrophages and T lymphocytes. In this study, we were able to further explore the molecular basis of its inhibitory mechanism using a butanol fraction of this herbal (Cb-BF) preparation. Similarly, this fraction also blocked the expression of cytokines such as IL-12 and tumor necrosis factor (TNF)-alpha as well as the proliferation of splenic lymphocytes and their production of IFN-gamma but not IL-4. Cb-BF suppressed the luciferase activities that are mediated by nuclear factor (NF)-kappaB, activator protein (AP)-1, and signal transducers and activators of transcription (STAT)-1. In agreement with this, these fractions diminished the translocation of the transcription factors into the nucleus. The study also demonstrated that the upstream signaling events for the activation of these factors such as spleen tyrosine kinase (Syk), janus kinase (JAK)-2, and extracellular signal-regulated kinase (ERK) were suppressed. Therefore, these results suggest that the butanol extract of Cordyceps bassiana may contain more than one active component capable of inhibiting the inflammatory signaling cascade and this can be considered as a potential candidate for treatment of diseases that require suppression of immune system.
Asunto(s)
Cordyceps/química , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Animales , Western Blotting , Butanoles , Colorantes , Genes Reporteros/efectos de los fármacos , Humanos , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-4/biosíntesis , Lipopolisacáridos/farmacología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Extractos Vegetales/farmacología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Solventes , Bazo/citología , Bazo/efectos de los fármacos , Sales de Tetrazolio , Tiazoles , Factores de Transcripción , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesisRESUMEN
Cordyceps species have been known as ethnopharmacologically valuable mushroom in Korea, China, and Japan. This plant has been reported to exhibit a variety of pharmacological activities such as antioxidative, anticancer, anti-inflammatory, antidiabetic, and antiobesity effects. Although numerous pharmacological potentials of Cordyceps spp. have been demonstrated, immunomodulatory effect of Cordyceps bassiana has not been published yet. To evaluate its immunomodulatory activity, macrophages activated by lipopolysaccharide (LPS) were employed and the production of interleukin-12 (IL-12) was explored in terms of understanding its molecular inhibitory mechanism. Seventy percent of ethanol extract from Cordyceps bassiana (Cb-EE) was able to suppress the expression of IL-12, a cytokine regulating interferon-γ (IFN-γ)-producing T helper type 1 (Th1) polarization response, at the transcriptional levels. The inhibitory effect of Cb-EE seemed to be due to activator protein-1 (AP-1) translocation inhibition, according to immunoblotting analysis with nuclear fraction and luciferase assay. In agreement with this, Cb-EE strongly suppressed the phosphorylation of p38, a prime signal to stimulate AP-1 translocation and IL-12 production, strongly suppressed by SB203580, a p38 inhibitor. Furthermore, this extract also suppressed IFN-γ production in both phytohemaglutinin A and LPS-activated splenocytes. Our results suggest that Cb-EE can be applied as a Th1 response regulatory herbal medicine.
Asunto(s)
Cordyceps/química , Factores Inmunológicos/farmacología , Interleucina-12/biosíntesis , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/fisiología , Etanol , Células HEK293 , Humanos , Immunoblotting , Factores Inmunológicos/aislamiento & purificación , Interferón gamma/biosíntesis , Interleucina-12/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Luciferasas/genética , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo/citología , Bazo/efectos de los fármacos , Bazo/inmunología , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/fisiología , TransfecciónRESUMEN
ETHNOPHARMACOLOGICAL SIGNIFICANCE: The Cordyceps species are insect-borne mushrooms that have been ethnopharmacologically used for skin diseases such as eczema and dermatitis. AIM OF THE STUDY: In this study, we investigated the curative effects of the butanol fraction (CBBF) of Cordyceps bassiana on atopic dermatitis. MATERIALS AND METHODS: Dermatitis was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. After a topical application of CBBF on the skin lesions, the dermatitis score, epidermal thickness, mast cell number, and interleukin (IL)-4 and interferon (IFN)-γ, as well as the levels of histamine and immunoglobulin E (IgE) in the serum, were measured. Moreover, effect of CBBF on histamine release was examined using RBL-2H3 under stimulation with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA). RESULTS: CBBF inhibited atopic dermatitis symptoms and signs in the DNFB-treated NC/Nga mice. The suppressive activity of topically applied CBBF may be due to the dose-dependent blockade of a series of immunopathological events, including the release of histamine, the production of IgE, and the secretion of IL-4 and IFN-γ. However, this extract did not directly suppress the degranulation process, assessed by measuring ß-hexosaminidase release. CONCLUSIONS: Our results suggest that CBBF can be applied as an effective herbal remedy to treat atopic dermatitis.