RESUMEN
The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects.
Asunto(s)
Zingiber officinale , alfa-Defensinas , Ratones , Animales , Muramidasa , Claudina-1/genética , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Antibacterianos/efectos adversos , AzúcaresRESUMEN
This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases.
Asunto(s)
FN-kappa B , Piranocumarinas , Humanos , FN-kappa B/metabolismo , Piranocumarinas/uso terapéutico , Lipopolisacáridos/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/metabolismo , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.
Asunto(s)
Interleucina-6 , Factor de Necrosis Tumoral alfa , Interleucina-6/genética , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Macrófagos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , FN-kappa B/metabolismo , ARN Mensajero/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An Aquimarina sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C (1), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, ent-caprolactin C (2), was synthesized. Both 1 and 2 inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-ß (TGF-ß)-treated A549 cells, 2 inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, ß-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound 1 did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound 2 could be a potential candidate for antimetastatic agent development, because it suppresses TGF-ß-induced EMT.
Asunto(s)
Antineoplásicos/farmacología , Caproatos/farmacología , Flavobacteriaceae/química , Lactonas/farmacología , Células A549 , Animales , Organismos Acuáticos , Línea Celular Tumoral/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
To increase the contents of medicinally effective ginsenosides, we used high-temperature and high-pressure thermal processing of ginseng by exposing it to microwave irradiation. To determine the anti-melanoma effect, the malignant melanoma SK-MEL-2 cell line was treated with an extract of microwave-irradiated ginseng. Microwave irradiation caused changes in the ginsenoside contents: the amounts of ginsenosides Rg1, Re, Rb1, Rb2, Rc, and Rd were disappeared, while those of less polar ginsenosides, such as Rg3, Rg5, and Rk1, were increased. In particular, the contents of Rk1 and Rg5 markedly increased. Melanoma cells treated with the microwave-irradiated ginseng extract showed markedly increased cell death. The results indicate that the microwave-irradiated ginseng extract induced melanoma cell death via the apoptotic pathway and that the cytotoxic effect of the microwave-irradiated ginseng extract is attributable to the increased contents of specific ginsenosides.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Ginsenósidos/farmacología , Melanoma/tratamiento farmacológico , Microondas , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ginsenósidos/química , Ginsenósidos/aislamiento & purificación , Glicosilación , Humanos , Melanoma/patología , Estructura Molecular , Panax/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD.
Asunto(s)
Antiinflamatorios/farmacología , Evaluación Preclínica de Medicamentos , Extractos Vegetales/farmacología , Animales , Colitis/tratamiento farmacológico , Colitis/etiología , Colitis/metabolismo , Colitis/patología , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Células Epiteliales/metabolismo , Femenino , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Ratones , Monocitos/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Glutamate-induced excitotoxicity and oxidative stress is a major causative factor in neuronal cell death in acute brain injuries and chronic neurodegenerative diseases. The prevention of oxidative stress is a potential therapeutic strategy. Therefore, in the present study, we aimed to examine a potential therapeutic agent and its protective mechanism against glutamate-mediated cell death. We first found that chebulinic acid isolated from extracts of the fruit of Terminalia chebula prevented glutamate-induced HT22 cell death. Chebulinic acid significantly reduced intracellular reactive oxygen species (ROS) production and Ca2+ influx induced by glutamate. We further demonstrated that chebulinic acid significantly decreased the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38, as well as inhibiting pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 protein expression. Moreover, we demonstrated that chebulinic acid significantly reduced the apoptosis induced by glutamate in HT22 cells. In conclusion, our results in this study suggest that chebulinic acid is a potent protectant against glutamate-induced neuronal cell death via inhibiting ROS production, Ca2+ influx, and phosphorylation of MAPKs, as well as reducing the ratio of Bax to Bcl-2, which contribute to oxidative stress-mediated neuronal cell death.
Asunto(s)
Calcio/metabolismo , Ácido Glutámico/metabolismo , Taninos Hidrolizables/farmacología , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frutas/química , Humanos , Taninos Hidrolizables/química , Taninos Hidrolizables/aislamiento & purificación , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Estructura Molecular , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Relación Estructura-Actividad , Terminalia/químicaRESUMEN
Metastasis is responsible for the great majority of deaths in cancer patients. Matrix metalloproteinases (MMPs) have critical functions in cancer metastasis. Especially, MMP-2 and MMP-9 play a major role in tumor-cell migration and invasion. Therefore, to first find out the inhibitory effect of eupatilin on expression of MMPs in SNU182 cells, we used quantitative real-rime PCR to measure MMP-2 and MMP-9 mRNA levels. Eupatilin suppressed transcription of MMP-2 in SNU182 cells more than did the corresponding controls. Also, eupatilin significantly blocked tube formation when treated with a concentration of 3.125 or 6.25⯵g/mL on human umbilical vein vascular endothelial cells (HUVECs). Eupatilin induced significant anti-angiogenic potential associated with down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated Akt expression. Thus, tube-formation inhibition and MMP-2-mediated migration are likely to be important therapeutic targets of eupatilin in hepatocellular carcinoma metastasis.
Asunto(s)
Carcinoma Hepatocelular/secundario , Flavonoides/farmacología , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Metástasis de la Neoplasia/prevención & control , Neovascularización Patológica/prevención & control , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/metabolismo , Metaloproteinasa 2 de la Matriz/genéticaRESUMEN
Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.
Asunto(s)
Colletotrichum/química , Morus/química , Fármacos Neuroprotectores/química , Animales , Antraquinonas/química , Antraquinonas/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
LC/MS-based phytochemical analysis of an EtOH extract of the roots of rice (Oryza sativa; Gramineae), which takes a crucial role in the stable crop population in Asia, resulted in the isolation of a new lignan, oryzativol C (1), as a minor component. The chemical structure of compound 1 was unambiguously confirmed using spectroscopic evidence (including 1D- and 2D-NMR data), HR-ESI-MS, and CD data analysis. Considering the traditional medicinal efficacy of O. sativa and its importance as a food crop, compound 1 was evaluated for effects on breast cancer cell lines (MDA-MB-231) and on glucose-stimulated insulin secretion in an INS-1 pancreatic ß-cell line. Compound 1 showed mild cytotoxicity toward the MDA-MB-231. Furthermore, compound 1 stimulated insulin secretion in INS-1 pancreatic ß-cells without inducing cytotoxicity. These results indicate that compound 1 is an active ingredient of O. sativa that offers health benefits including inhibition of breast cancer cell proliferation and hyperglycemia control.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Lignanos/farmacología , Oryza/química , Raíces de Plantas/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Lignanos/química , Lignanos/aislamiento & purificación , Conformación Molecular , Relación Estructura-ActividadRESUMEN
Shiunko ointment is composed of five ingredients including Lithospermi Radix (LR), Angelicae Gigantis Radix, sesame seed oil, beeswax, and swine oil. It is externally applied as a treatment for a wide range of skin conditions such as eczema, psoriasis, hair loss, burns, topical wounds, and atopic dermatitis. Deoxyshikonin is the major angiogenic compound extracted from LR. In this study, we investigated the efficacy of LR extract and deoxyshikonin on impaired wound healing in streptozotocin (STZ)-induced diabetic mice. Treatment with LR extract elevated tube formation in human umbilical vein endothelial cells (HUVECs) and exerted antioxidant activity. An open skin wound was produced on the backs of diabetic mice and was then topically treated with deoxyshikonin or vehicle. In addition, deoxyshikonin promoted tube formation in high glucose conditions exposed to HUVECs, and which may be regulated by increased VEGFR2 expression and phosphorylation of Akt and p38. Our results demonstrate that deoxyshikonin application promoted wound repair in STZ-induced diabetic mice. Collectively, these data suggest that deoxyshikonin is an active ingredient of LR, thereby contributing to wound healing in patients with diabetes.
Asunto(s)
Diabetes Mellitus Experimental/patología , Naftoquinonas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Lithospermum/química , Masculino , Ratones , Ratones Endogámicos ICR , Neovascularización Fisiológica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Aucklandia lappa DC., Terminalia chebula Retz and Zingiber officinale Roscoe have been traditionally used in east Asia to treat chronic diarrhea and abdominal pain. This study aimed to evaluated the anti-inflammatory activity of KM1608, which is composed of three natural herbs in a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis. The anti-inflammatory activity and underlying mechanism were assessed in vitro using LPS-treated RAW264.7 cells. The in vivo effect of KM1608 on DSS-induced colitis was examined after oral administration in mice. KM1608 significantly inhibited the inflammatory mediators such as nitric oxide, interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor (TNF)-α in LPS-treated RAW264.7 cells. The inhibitory effect of KM1608 was attributed to the reduction of Akt phosphorylation in the LPS-treated cells. In the mouse model, oral administration of KM1608 significantly improved DSS-induced colitis symptoms, such as disease activity index (DAI), colon length, and colon weight, as well as suppressed the expression of IL-6, TNF-α, and myeloperoxidase (MPO) in the DSS-induced colitis tissues. Taken together, KM1608 improved colitis through the regulation of inflammatory responses, suggesting that KM1608 has potential therapeutic use in the treatment of inflammatory diseases.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/análisis , Cromatografía Líquida de Alta Presión , Colitis/tratamiento farmacológico , Colitis/etiología , Colitis/patología , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Ratones , Oxidación-Reducción/efectos de los fármacos , Fosforilación/efectos de los fármacos , Fitoquímicos/análisis , Extractos Vegetales/análisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7RESUMEN
In this study, we investigated the anti-inflammatory effects and mechanisms of cirsimaritin isolated from an ethanol extract of the aerial parts of Cirsium japonicum var. maackii Maxim. using RAW264.7 cells. The extract and its flavonoid cirsimaritin inhibited nitric oxide (NO) production and inducible nitric oxide synthase expression in RAW264.7 cells. Cirsimaritin inhibited interleukin-6, tumor necrosis factor-α, and NO production in a concentration-dependent manner in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. From a western blot study, pretreatment with cirsimaritin inhibited phosphorylation/degradation of IκBα and phosphorylation of Akt in LPS-stimulated RAW264.7 cells. Moreover, cirsimaritin suppressed activation of LPS-induced transcription factors, such as c-fos and signal transducer and activator of transcription 3 (STAT3), in RAW264.7 cells. Collectively, these results show that cirsimaritin possesses anti-inflammatory activity, which is regulated by inhibition of c-fos and STAT3 phosphorylation in RAW264.7 cells.
Asunto(s)
Antiinflamatorios/química , Cirsium/química , Flavonas/química , Extractos Vegetales/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Cirsium/metabolismo , Flavonas/aislamiento & purificación , Flavonas/farmacología , Interleucina-6/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Inhibidor NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Células RAW 264.7 , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound isolated from Flos Chrysanthemi Indici, chrysanthemum, safflower, and Calamintha and Linaria species has been shown to have anti-cancer activity, indicating its potential clinical value in cancer treatment. In this study, we sought to study the potentials of acacetin in preventing human dopaminergic neuronal death via inhibition of 6-hydroxydopamine (6-OHDA)-induced neuronal cell death in the SH-SY5Y cells. Our results suggest that acacetin was effective in preventing 6-OHDA-induced neuronal cell death through regulation of mitochondrial-mediated cascade apoptotic cell death. Pretreatment with acacetin significantly inhibited neurotoxicity and neuronal cell death through reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) dysfunction. Acacetin also markedly acted on key molecules in apoptotic cell death pathways and reduced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3beta (GSK-3ß). These results suggested that acacetin could inhibit 6-OHDA-induced neuronal cell death originating from ROS-mediated cascade apoptosis pathway. Thus, the results of our study suggest that acacetin is a potent therapeutic agent for PD progression.
Asunto(s)
Flavonas/farmacología , Neuronas/efectos de los fármacos , Oxidopamina/antagonistas & inhibidores , Enfermedad de Parkinson/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flavonas/química , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Neuronas/patología , Oxidopamina/farmacología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
Epidermal growth factor receptor (EGFR) mutation is one of the hallmarks of cancer progression and resistance to anticancer therapies, particularly non-small cell lung carcinomas (NSCLCs). In contrast to the canonical EGFR activation in which tyrosine residues are engaged, we have demonstrated that the non-canonical pathway is triggered by phosphorylation of serine and threonine residues through p38 and ERK MAPKs, respectively. The purpose of this study is to investigate the role of non-canonical EGFR pathway in resistance mechanism against cisplatin treatment. Wild type and mutated (exon 19 deletion) EGFR-expressing cells responded similarly to cisplatin by showing MAPK-mediated EGFR phosphorylation. It is interesting that internalization mechanism of EGFR was switched from tyrosine kinase-dependent to p38-dependent fashions, which is involved in a survival pathway that counteracts cisplatin treatment. We therefore introduce a potential combinatorial therapy composed of p38 inhibition and cisplatin to block the activation of EGFR, therefore inducing cancer cell death and apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Cisplatino/farmacología , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos , Receptores ErbB/metabolismo , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mutación , Fosforilación/efectos de los fármacosRESUMEN
BACKGROUND: The interaction of Helicobacter pylori with gastric epithelial cells can result in the activation of transcription factor NF-κB via TGF-ß-activated kinase 1 (TAK1). In this study, we have demonstrated the role of H. pylori in the activation of EGFR via TAK1-mediated phosphorylation of p38. MATERIALS AND METHODS: Gastric epithelial AGS or MKN-45 cells were co-cultured with wild-type or cagA(-) H. pylori strains. H. pylori was added to the cells, and the activation of EGFR, p65 (NF-κB) subunit, p38, ERK, and TAK1 was examined by Western blotting. Infected cells were pretreated with or without ligands, chemical inhibitors, anti-HB-EGF antibody, and siRNAs to evaluate the effects on phosphorylation of various EGFR residues. Fluorescence microscopy and flow cytometry were performed to detect the internalization of EGFR. RESULTS: Incubating cells with wild-type and CagA(-) H. pylori strains resulted in the rapid and transient phosphorylation of serine residues of EGFR. RNAi experiments using siRNA against TAK1 and p38 pathways blocked the phosphorylation of serine residue. Immunofluorescence and flow cytometry revealed that EGFR was internalized in H. pylori-infected cells after EGFR phosphorylation in a p38-dependent manner. In contrast, pretreatment with gefitinib and anti-HB-EGF antibody did not block both the phosphorylation and internalization of EGFR. CONCLUSION: Helicobacter pylori induces internalization of EGFR via novel TAK1-p38-serine activation pathway which is independent of HB-EGF. The interaction between TAK1 and EGFR in H. pylori-infected cells might open new dimensions in understanding H. pylori-associated gastric carcinogenesis.
Asunto(s)
Receptores ErbB/metabolismo , Helicobacter pylori/metabolismo , Interacciones Huésped-Patógeno , Quinasas Quinasa Quinasa PAM/metabolismo , Procesamiento Proteico-Postraduccional , Serina/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Western Blotting , Línea Celular , Técnicas de Cocultivo , Citometría de Flujo , Humanos , Microscopía Fluorescente , FosforilaciónRESUMEN
Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.
Asunto(s)
Bombyx , Menopausia , Ovariectomía , Transducción de Señal , Animales , Femenino , Menopausia/efectos de los fármacos , Ratones , Transducción de Señal/efectos de los fármacos , Estradiol/sangre , Receptor alfa de Estrógeno/metabolismo , Útero/efectos de los fármacos , Fosforilación , Modelos Animales de Enfermedad , Polvos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
Brain plasticity refers to the brain's ability to modify its structure, accompanied by its functional changes. It is influenced by learning, experiences, and dietary factors, even in later life. Accumulated researches have indicated that ginseng may protect the brain and enhance its function in pathological conditions. There is a compelling need for a more comprehensive understanding of ginseng's role in the physiological condition because many individuals without specific diseases seek to improve their health by incorporating ginseng into their routines. This review aims to deepen our understanding of how ginseng affects brain plasticity of people undergoing normal aging process. We provided a summary of studies that reported the impact of ginseng on brain plasticity and related factors in human clinical studies. Furthermore, we explored researches focused on the molecular mechanisms underpinning the influence of ginseng on brain plasticity and factors contributing to brain plasticity. Evidences indicate that ginseng has the potential to enhance brain plasticity in the context of normal aging by mediating both central and peripheral systems, thereby expecting to improve age-related declines in brain function. Moreover, given modern western diet can damage neuroplasticity in the long term, ginseng can be a beneficial supplement for better brain health.
RESUMEN
This study evaluated the ameliorative effects of Korean-red-ginseng-derived polysaccharide (KRG-P) on antibiotic-associated diarrhea (AAD) induced by administering lincomycin in mice. Changes of intestinal barrier proteins, the intestinal microbiome and short-chain fatty acid (SCFA) contents were investigated. Lincomycin was orally administered for 9 days to induce diarrhea; subsequently, 100 mg/kg and 300 mg/kg of KRG-P were administered orally for 12 days. The diarrhea was observed in the AAD group; further KRG-P administration improved the diarrhea. Analysis of changes in the intestinal microbial flora of the mice revealed that the harmful bacterial flora (such as Proteobacteria) were increased in the AAD group, whereas beneficial bacterial flora (such as Firmicutes) were decreased. However, KRG-P administration resulted in decreased Proteobacteria and increased Firmicutes, supporting the improvement of the microbial flora imbalance caused by AAD. Moreover, an analysis of the SCFAs (acetic acid, propionic acid, and butylic acid) in the caecum revealed that SCFAs' contents in the AAD group were substantially reduced but tended to increase upon KRG-P administration. Based on these results, KRG-P, which is primarily composed of carbohydrates can improve lincomycin-induced diarrhea, likely owing to the recovery of SCFA content by improving the intestinal microbial imbalance and intestinal barrier proteins.