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1.
J Med Food ; 26(12): 927-938, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38064431

RESUMEN

Cisplatin, a potent and prominent chemotherapeutic drug, has considerable side effects, including nephrotoxicity, which limits its therapeutic application and efficacy. Therefore, the development of agents that protect normal cells while preserving cisplatin's chemotherapeutic properties is of utmost importance. This study aimed to explore the protective effects of Bombyx batryticatus protein-rich extract (BBPE) against cisplatin-induced nephrotoxicity in a cisplatin-treated mouse model and human embryonic kidney (HEK293) cells. Apoptosis was assessed in HEK293 cells to determine the cytoprotective effects of BBPE and its effects on the generation of cisplatin-induced reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) collapse. Although cisplatin induced nephrotoxicity in HEK293 cells, pretreatment with BBPE showed significant protective effects against cisplatin-induced nephrotoxicity by regulating the expression levels of pro- and antiapoptotic proteins. The cytoprotective effects of BBPE were mediated by decreased ROS production and MTP loss in cisplatin-treated HEK293 cells. The in vitro results were confirmed in the cisplatin-treated mouse model. Pretreatment with BBPE protected against cisplatin-induced nephrotoxicity by restoring malondialdehyde, superoxide dismutase, and catalase levels in kidney tissue and blood urea nitrogen and creatinine serum levels. Furthermore, histopathological assessment and terminal dUTP nick end-labeling staining showed that BBPE mitigated cisplatin-induced nephrotoxicity in kidney tissues. Overall, BBPE may act as a potent agent for alleviating cisplatin-induced nephrotoxicity, thereby increasing the safety of cisplatin-based chemotherapy.


Asunto(s)
Bombyx , Cisplatino , Ratones , Animales , Humanos , Cisplatino/efectos adversos , Células HEK293 , Especies Reactivas de Oxígeno/metabolismo , Bombyx/metabolismo , Estrés Oxidativo , Glutatión/metabolismo , Riñón , Apoptosis
2.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34299130

RESUMEN

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.


Asunto(s)
Cisplatino/toxicidad , Frutas/química , Macrófagos/efectos de los fármacos , Melanoma Experimental/tratamiento farmacológico , Moraceae/química , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Antineoplásicos/toxicidad , Apoptosis , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Macrófagos/patología , Melanoma Experimental/inducido químicamente , Melanoma Experimental/patología , Potencial de la Membrana Mitocondrial , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Sustancias Protectoras/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Molecules ; 26(2)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33477499

RESUMEN

Bombyx batryticatus, a protein-rich edible insect, is widely used as a traditional medicine in China. Several pharmacological studies have reported the anticancer activity of B. batryticatus extracts; however, the capacity of B. batryticatus extracts as immune potentiators for increasing the efficacy of cancer immunotherapy is still unverified. In the present study, we investigated the immunomodulatory role of B. batryticatus protein-rich extract (BBPE) in bone marrow-derived dendritic cells (BMDCs) and DC vaccine-immunized mice. BBPE-treated BMDCs displayed characteristics of mature immune status, including high expression of surface molecules (CD80, CD86, major histocompatibility complex (MHC)-I, and MHC-II), increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-12p70), enhanced antigen-presenting ability, and reduced endocytosis. BBPE-treated BMDCs promoted naive CD4+ and CD8+ T-cell proliferation and activation. Furthermore, BBPE/ovalbumin (OVA)-pulsed DC-immunized mice showed a stronger OVA-specific multifunctional T-cell response in CD4+ and CD8+ T cells and a stronger Th1 antibody response than mice receiving differently treated DCs, which showed the enhanced protective effect against tumor growth in E.G7 tumor-bearing mice. Our data demonstrate that BBPE can be a novel immune potentiator for a DC-based vaccine in anticancer therapy.


Asunto(s)
Adyuvantes Inmunológicos , Presentación de Antígeno/inmunología , Vacunas contra el Cáncer/inmunología , Células Dendríticas/fisiología , Proteínas de Insectos/metabolismo , Células TH1/inmunología , Extractos de Tejidos/farmacología , Animales , Bombyx , Proliferación Celular , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Femenino , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
4.
Nutrients ; 12(11)2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33105813

RESUMEN

Oxya chinensis sinuosa (Ocs) is consumed as representative edible insects in Asia, but its function in various immune systems remains unclear. This study aimed to demonstrate the immunomodulatory effect, particularly on the innate and adaptive immune response, of Ocs protein (Ocs-P) and to investigate its function as a potent anticancer immunostimulant when administered during the progression stage of colon carcinoma in tumor-bearing mice. Our in vitro results demonstrated that Ocs-P treatment induces phenotypic alteration (increased expression of surface molecules and production of Th1-polarizing cytokines and decreased antigen uptake ability) of dendritic cells (DCs) through the activation of MAPK and NF-κB-dependent signaling pathways. Additionally, Ocs-P-stimulated DCs initiated differentiation of naive T cells into IFN-γ-producing Th1-type T cells effectively and activated cytotoxic CD8+ T cell response. In colon carcinoma-bearing mouse models, oral administration of Ocs-P inhibited tumor growth and restored the expression of decreased surface molecules in lineage-CD11c+MHC-II+ splenic DCs. Furthermore, Ocs-P administration enhanced the generation of multifunctional CD4+ and CD8+ T cells expressing Th1-type cytokines (TNF-α, IFN-γ, and IL-2) and the degranulation marker (CD107a). Collectively, these results suggest that Ocs-P demonstrates an immunostimulatory effect and may induce powerful anticancer immunity.


Asunto(s)
Neoplasias del Colon/inmunología , Suplementos Dietéticos , Insectos Comestibles/química , Saltamontes/química , Proteínas de Insectos/inmunología , Proteínas de Insectos/farmacología , Inmunidad Adaptativa , Adyuvantes Inmunológicos , Animales , Neoplasias del Colon/dietoterapia , Neoplasias del Colon/patología , Citocinas/metabolismo , Células Dendríticas/inmunología , Femenino , Inmunidad Innata , Activación de Linfocitos , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos BALB C , Subunidad p50 de NF-kappa B/metabolismo , Transducción de Señal , Linfocitos T Citotóxicos/inmunología , Células TH1/inmunología
5.
Nutrients ; 12(6)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32486094

RESUMEN

Dendritic cells (DCs) are powerful antigen-presenting cells that are often used to evaluate adjuvants, particularly for adjuvant selection for various vaccines. Here, polysaccharides (named ALP) isolated from leaves of Annona muricata L., which are used in traditional medicine such as for bacterial infections and inflammatory diseases, were evaluated as an adjuvant candidate that can induce anti-tumor activity. We first confirmed the phenotypic (surface molecules, cytokines, antigen uptake, and antigen-presenting ability) and functional alterations (T cell proliferation/activation) of DCs in vitro. We also confirmed the adjuvant effect by evaluating anti-tumor activity and immunity using an ALP-treated DC-immunized mouse model. ALP functionally induced DC maturation by up-regulating the secretion of Th1-polarizing pro-inflammatory cytokines, the expression of surface molecules, and antigen-presenting ability. ALP triggered DC maturation, which is dependent on the activation of the MAPK and NF-κB signaling pathways. ALP-activated DCs showed an ample capacity to differentiate naive T cells to Th1 and activated CD8+ T cells effectively. The systemic administration of DCs that pulse ALP and ovalbumin peptides strongly increased cytotoxic T lymphocyte (CTL) activity (by 9.5% compared to that in the control vaccine groups), the generation of CD107a-producing multifunctional T cells, and Th1-mediated humoral immunity, and caused a significant reduction (increased protection by 29% over that in control vaccine groups) in tumor growth. ALP, which triggers the Th1 and CTL response, provides a basis for a new adjuvant for various vaccines.


Asunto(s)
Adyuvantes Inmunológicos , Annonaceae/química , Vacunas contra el Cáncer , Células Dendríticas/inmunología , Polisacáridos , Timoma/inmunología , Neoplasias del Timo/inmunología , Animales , Presentación de Antígeno , Citocinas/metabolismo , Femenino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Polisacáridos/inmunología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Linfocitos T/inmunología , Timoma/terapia , Neoplasias del Timo/terapia
6.
Biosci Biotechnol Biochem ; 84(5): 1001-1012, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31960754

RESUMEN

Crude extracts and phytochemical compounds derived from Annona muricata leaves have been demonstrated to exert neuroprotective effects. However, the neuroprotective effects of Annona muricata leaves-derived polysaccharide extracts (ALPs) have not been investigated. ALP treatment was shown to induce concentration-dependent antioxidant activity in HT22 cells, and to increase cell viability in H2O2-treated HT22 cells. These effects were correlated with a decrease in major components of oxidation, including: Ca2+, ROS, and malondialdehyde (MDA). Mediators of the intracellular response to oxidation, including Bax, cytochrome c, and cleaved caspases-3, -8, -9, MAPKs, and NF-κB, were positively influenced by ALP treatment under conditions of H2O2-mediated oxidative stress. In addition, ALP restored the expression of superoxide dismutase (SOD) and associated signaling pathways (PARP, PI3K/AKT and Nrf2-mediated HO-1/NQO-1) following H2O2 treatment. These results provide new pharmacological evidence that ALP facilitates neuroprotection via prevention of neuronal oxidative stress and promotion of cell survival signaling pathways.Abbreviations: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid); AD: Alzheimer's disease; ALP: polysaccharide extracts isolated from Annona muricata leaves; ARE: antioxidant response element; DPPH: 1,1-diphenyl-picrylhydrazyl; DCFH-DA: 2',7'-dichlorofluorescin diacetate; ECL: electrochemiluminescence; ERK: extracellular regulated kinase; FBS: Fetal bovine serum; FITC: fluorescein isothiocyanate; FRAP: ferric reducing antioxidant power; HO-1: Heme oxygenase-1; JNK: c-jun N-terminal kinase; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; MMP: mitochondrial membrane potential; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide; NQO1: NAD(P)H:quinine oxidoreductase 1, Nrf2: nuclear factor-E2-related factor 2; PD: parkinson's disease; PI3K: phosphatidylinositol-3kinase; PVDF: polyvinylidene difluoride; ROS: reactive oxygen species; SOD: Superoxidedismutase; TPTZ: tripydyltriazine.


Asunto(s)
Annona/química , Antioxidantes/farmacología , Peróxido de Hidrógeno/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Malondialdehído/análisis , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo
7.
Int Immunopharmacol ; 78: 106072, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31835082

RESUMEN

Although the novel resveratrol derivative RM has therapeutic potential for the treatment of inflammatory bowel disease, little is currently known regarding the manner whereby RM regulates excessive inflammatory responses. In this study, we initially investigated the molecular mechanisms underlying the anti-inflammatory effects induced by RM in Toll-like receptor (TLR)-activated macrophages. Upon stimulation with lipopolysaccharide, we found that RM-treated activated macrophages down-regulated the increase in pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-12p70), nitric oxide (NO) production, and activating interleukin-1 receptor-associated kinase 1 (IRAK-1) phosphorylation, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Interestingly, the TLR negative regulator Toll-interacting protein (Tollip) was selectively enhanced during RM stimulation in time- and dose-dependent manners. In response to knockdown of Tollip expression by RNA interference, RM-treated activated macrophages showed augmented expression of inflammatory mediators (pro-inflammatory cytokines, NO, inducible nitric oxidase, and cyclooxygenase-2, and surface molecules) and restored the expression of MAPK and NF-κB signals inhibited by RM treatment. Taken together, our findings indicate that RM has therapeutic potential for treating TLR-induced inflammatory diseases via the promotion of Tollip expression.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/efectos de los fármacos , Resveratrol/farmacología , Animales , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Rayos gamma , Técnicas de Silenciamiento del Gen , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/inmunología , Lipopolisacáridos/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Cultivo Primario de Células , Células RAW 264.7 , Resveratrol/análogos & derivados , Resveratrol/efectos de la radiación , Resveratrol/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Receptores Toll-Like/metabolismo , Regulación hacia Arriba
8.
J Med Food ; 22(7): 713-721, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31158040

RESUMEN

Irradiation technology can improve the biological activities of natural molecules through a structural modification. This study was conducted to investigate the enhancement of the anticancer effects of chrysin upon exposure to gamma irradiation. Gamma irradiation induces the production of new radiolytic peaks simultaneously with the decrease of the chrysin peak, which increases the cytotoxicity in HT-29 human colon cancer cells. An isolated chrysin derivative (CM1) exhibited a stronger apoptotic effect in HT-29 cells than intact chrysin. The apoptotic characteristics induced by CM1 in HT-29 cells was mediated through the intrinsic signaling pathway, including the excessive production of included reactive oxygen species, the dissipation of the mitochondrial membrane potential, regulation of the B cell lymphoma-2 family, activation of caspase-9, 3, and cleavage of poly (adenosine diphosphate-ribose) polymerase. Our findings suggest that CM1 can be a potential anticancer candidate for the treatment of colon cancer.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias del Colon/metabolismo , Flavonoides/farmacología , Mitocondrias/efectos de los fármacos , Antineoplásicos/efectos de la radiación , Caspasas/genética , Caspasas/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Flavonoides/efectos de la radiación , Rayos gamma , Células HT29 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
9.
Biosci Biotechnol Biochem ; 82(12): 2149-2157, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30227776

RESUMEN

Phenolic compounds isolated from pepper (Capsicum annum) have been demonstrated to have neuroprotective effects, whereas the physiological properties of Capsicum annuum var. abbreviatum (CAA) have not been studied. Thus, we investigate the chemical composition and neuroprotective activity of CAA extract (CAAE) in HT22 hippocampus cells against H2O2-induced neurotoxicity. CAAE treatment resulted in a significant protection of H2O2-exposed HT22, this protection ultimately occurred through an inhibition of MDA and ROS levels and an induction of SOD activity. Furthermore, CAAE treatment reduced H202-induced apoptosis though decreasing the expression of pro-apoptotic factors (Bax, cytochrome c, and cleaved caspases-3) while increasing the expression of the anti-apoptotic factors (Bcl-2), as well as the accumulation of nucleus-Nrf2-mediated HO-1 signaling. Interestingly, CAAE has a high concentration of unique phenolic compositions (chlrogenic acid, tangeretin, etc.) than other capsicum annum extracts. Altogether, these findings suggest that CAAE can be a useful natural resource for alleviating neurodegenerative diseases.


Asunto(s)
Capsicum/química , Hipocampo/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular , Cromatografía Líquida de Alta Presión , Citocromos c/metabolismo , Hemo-Oxigenasa 1/metabolismo , Hipocampo/citología , Hipocampo/enzimología , Hipocampo/metabolismo , Malondialdehído/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Fenoles/análisis , Fenoles/aislamiento & purificación , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
10.
Food Chem Toxicol ; 111: 133-143, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29126802

RESUMEN

Gamma irradiation is able to affect various structural modification and an increase of the biological properties of biomaterials. This study was conducted to investigate the anti-allergenic effect of γ-irradiated black ginseng extract (BGE) using in vitro and in vivo experiments. IgEantigen complex-induced degranulation was measured in RBL-2H3 mast cells. In addition, an anti-atopic dermatitis (AD) test was carried out by spreading γ-irradiated BGE on the dorsal skin of 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice. The content of arginylfructose (AF) of gamma-irradiated BGE was higher than that of BGE. In RBL-2H3 mast cells, γ-irradiated BGE treatments significantly reduced the IgE-antigen complex-induced release of ß-hexosaminidase, histamine, intracellular ROS, and Ca2+ influx. A western blot analysis showed that γ-irradiated BGE had an inhibitory activity on the FcεRI-mediated signaling in mast cells. In the DNCB-induced AD model, γ-irradiated BGE significantly alleviated the ADlike skin symptoms and clinical signs. The suppression of AD by γ-irradiated BGE was accompanied by a decrease in the serum level of IgE and IL-4, as well as the number of leukocyte. Gamma-irradiated BGE also suppressed IL-4 and increased IFN-γ in splenocytes. Our data suggests that γ-irradiated BGE may be effective therapeutic agents for the treatment of AD.


Asunto(s)
Supervivencia Celular/efectos de los fármacos , Dermatitis Atópica/prevención & control , Rayos gamma , Mastocitos/efectos de los fármacos , Panax/química , Extractos Vegetales/química , Animales , Técnicas de Cultivo de Célula , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Dinitroclorobenceno/toxicidad , Femenino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/efectos de la radiación
11.
J Med Food ; 20(8): 812-819, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28753056

RESUMEN

Luteolin was gamma irradiated at doses of 0, 15, 30, 50, 70, and 100 kGy. We observed that the luteolin peak decreased simultaneously with the appearance of new radiolytic peaks, using high-performance liquid chromatography (HPLC). The highest new radiolytic peak (GLM) of radiolytic product in gamma-irradiated luteolin was observed at a dose of 70 kGy, and the GLM was identified by nuclear magnetic resonance and high-performance-liquid-chromatography-quadrupole-time-of-flight (HPLC-Q-TOF) mass spectrometry. We examined whether 70 kGy gamma-irradiated luteolin has more effective anti-melanogenic effects than intact luteolin. Seventy kilograys of gamma-irradiated luteolin inhibited melanin synthesis and intracellular tyrosinase activity without cytotoxicity, whereas the intact luteolin-treated group did not show anti-melanogenic activity in 3-isobutyl-1-methylxanthine-stimulated B16BL6 melanoma cells. The expression of melanogenic enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, was decreased by 70 kGy gamma-irradiated luteolin treatment, owing to the suppression of microphthalamia-associated transcription factor and 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein. In addition, gamma-irradiated luteolin decreased the phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and extracellular regulated kinase (ERK). The anti-melanogenic effects of 70 kGy gamma-irradiated luteolin were attenuated by the treatment of two specific inhibitors (PD98059 and LY294002), and these results indicate that the anti-melanogenic effects were mediated by ERK and PI3K signaling pathways. Therefore, our findings suggest that gamma-irradiated luteolin can be a potential cosmeceutical agent for skin whitening.


Asunto(s)
1-Metil-3-Isobutilxantina/toxicidad , Luteolina/farmacología , Melaninas/metabolismo , Melanoma/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Rayos gamma , Humanos , Luteolina/efectos de la radiación , Melanoma/inducido químicamente , Melanoma/genética , Ratones , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/genética , Monofenol Monooxigenasa/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo
12.
Am J Chin Med ; 44(5): 1009-26, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27430908

RESUMEN

An effective method for activating macrophages and deriving a Th1 immune response could be used to improve the defenses of hosts. In this study, we investigated the immunomodulation effect and the related signaling mechanism of [Formula: see text]-(1,3)-glucan, isolated from the Agrobacterium species. Here, we found that [Formula: see text]-(1,3)-glucan predominantly induced the tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], IL-6, IL-12p70, and nitric oxide, which was dependent on mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-[Formula: see text]B signaling. Additionally, [Formula: see text]-(1,3)-glucan treatment significantly up-regulated the expression of the co-stimulatory molecules CD80 and CD86, and also significantly increased the expression of iNOS and Dectin-1, which is a transmembrane protein that binds [Formula: see text]-glucan and associates with macrophage activation. Importantly, the splenic T cells co-cultured with [Formula: see text]-(1,3)-glucan-treated macrophages produced the a Th1 cytokine profile that includes high levels of IFN-[Formula: see text], but not IL-4 (Th2 cytokine), indicating that [Formula: see text]-(1,3)-glucan contributes to Th1 polarization of the immune response. Taken together, our results suggest that [Formula: see text]-(1,3)-glucan isolated from Agrobacterium species can induce macrophage activation through the MAPK and NF-[Formula: see text]B signaling pathway, as well as Th1 polarization.


Asunto(s)
Agrobacterium/química , Glucanos/farmacología , Factores Inmunológicos/farmacología , Macrófagos/efectos de los fármacos , Bazo/citología , Agrobacterium/metabolismo , Animales , Células Cultivadas , Glucanos/aislamiento & purificación , Glucanos/metabolismo , Factores Inmunológicos/aislamiento & purificación , Factores Inmunológicos/metabolismo , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-1/genética , Interleucina-1/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Activación de Macrófagos , Macrófagos/inmunología , Ratones , FN-kappa B/genética , FN-kappa B/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología
13.
J Med Food ; 17(7): 742-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24971771

RESUMEN

The aim of this study was to clarify the efficacy of procyanidin C1 (Pro C1) for modulating vascular tone. Pro C1 induced a potent vasorelaxant effect on phenylephrine-constricted endothelium-intact thoracic aortic rings, but had no effect on denuded thoracic aortic rings. Moreover, Pro C1 caused a significant increase in nitric oxide (NO) production in endothelial cells. Pro C1-induced vasorelaxation and Pro C1-induced NO production were significantly decreased in the presence of a nonspecific potassium channel blocker (tetraethylammonium chloride [TEA]), an endothelial NO synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), and a store-operated calcium entry inhibitor (2-aminoethyl diphenylborinate [2-APB]). Pro C1-induced vasorelaxation was also completely abolished by an inhibitor of soluble guanyl cyclase, which suggests that the Pro C1 effects observed involved cyclic guanosine monophosphate (cGMP) production. Interestingly, Pro C1 significantly enhanced basal cGMP levels. Taken together, these results indicate that Pro C1-induced vasorelaxation is associated with the activation of the calcium-dependent NO/cGMP pathway, involving potassium channel activation. Thus, Pro C1 may represent a novel and potentially therapeutically relevant compound for the treatment of cardiovascular diseases.


Asunto(s)
Biflavonoides/farmacología , Catequina/farmacología , GMP Cíclico/metabolismo , Óxido Nítrico/metabolismo , Proantocianidinas/farmacología , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Animales , Aorta Torácica/efectos de los fármacos , Compuestos de Boro/farmacología , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Técnicas In Vitro , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Bloqueadores de los Canales de Potasio/farmacología , Ratas , Ratas Sprague-Dawley , Tetraetilamonio/farmacología , Vasodilatadores/farmacología , omega-N-Metilarginina/farmacología
14.
Biochem Biophys Res Commun ; 426(4): 480-5, 2012 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-22960171

RESUMEN

Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to down-regulate inflammatory responses in dendritic cells (DCs); however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor. In this study, we showed the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by EGCG in DCs. The expressions of CD80, CD86, and MHC class I and II, which are molecules essential for antigen presentation by DCs, were inhibited by EGCG via 67LR. In addition, EGCG-treated DCs inhibited lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, and IL-6) and activation of mitogen-activated protein kinases (MAPKs), e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) p65 translocation through 67LR. Interestingly, we also found that EGCG markedly elevated the expression of the Tollip protein, a negative regulator of TLR signaling, through 67LR. These novel findings provide new insight into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and consequent inflammatory responses that are implicated in the development and progression of many chronic diseases.


Asunto(s)
Camellia sinensis , Catequina/análogos & derivados , Células Dendríticas/efectos de los fármacos , Receptores de Laminina/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Catequina/farmacología , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/inmunología , Inflamación/inmunología , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Lipopolisacáridos/inmunología , Ratones , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba
15.
J Nutr Biochem ; 23(3): 278-86, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21543207

RESUMEN

Apple procyanidins (AP), one of the polyphenol-rich compounds, showed an endothelial-dependent vasorelaxation in rat aorta, but the mechanisms of beneficial effects are still unclear. The present study was designed to clarify the potential role of AP in rat aorta endothelial cells (RAECs). The treatment of RAECs with AP (1-10 µg/ml) resulted in a dose-dependent hyperpolarization with a maximum effect at 10 µg/ml, and for this reason, AP (10 µg/ml) was used in all the following experiments. AP-induced hyperpolarization was significantly inhibited by pretreatment of nonspecific K(+) inhibitor, tetraethyl ammonium chloride or specific K(+) channel inhibitors, iberiotoxin, glibenclamide, 4-aminopyridine and BaCl(2), as well as by high KCl or Ca(2+)-free solution. AP-induced hyperpolarization was also proved using 64-channel multielectrode dish system that can monitor a direct and real-time change of membrane potential. Furthermore, AP treatment caused a significant increase of nitric oxide (NO) production and cyclic guanosine monophosphate levels via endothelial NO synthase messenger RNA expression. The NO production was inhibited by N(G)-monoethyl-l-arginine or Ca(2+)-free solution and was completely abolished by their combination. Also, AP inhibited endothelial proliferation, while the effect was significantly abolished by N(G)-monoethyl-l-arginine or tetraethyl ammonium chloride. These findings suggest that AP induces both hyperpolarization of RAECs via multiple activation of K(+) channels and activation of NO/cyclic guanosine monophosphate pathway via increasing NO production or is responsible for antiangiogenic effect. Diminishment of hyperpolarization as well as NO production of AP in Ca(2+)-free solution implicated that AP would play a crucial role in promoting Ca(2+) influx into endothelial cells so as to promote both actions.


Asunto(s)
Aorta/efectos de los fármacos , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Malus/química , Extractos Vegetales/farmacología , Canales de Potasio/metabolismo , Proantocianidinas/farmacología , Animales , Aorta/metabolismo , Proliferación Celular , GMP Cíclico/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Frutas/química , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Potenciales de la Membrana/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Bloqueadores de los Canales de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Vasodilatación/efectos de los fármacos
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