RESUMO
BACKGROUND: Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes). METHODS: First, using human hair follicle (HF) dermal papilla cells (hDPCs) treated with ASC-Exosomes, ALP, VCAN, ß-catenin, and LEF-1 levels with RT-PCR and p-GSK3ß, GSK3ß, ß-catenin, ALP, and ß-actin levels with western blot analysis were assessed. Hair shaft elongation test and assay for ALP, Ki-67, and ß-catenin were done using human HF organ culture. Patients with AGA had ASC-Exosomes treatment and were evaluated for hair counts, photographic assessments, subjective satisfaction, and safety profiles. RESULTS: ASC-Exosomes impact hDPCs, increasing proliferation and the upregulation of hair growth-related genes, including ALP, VCAN, ß-catenin, and LEF-1. The Wnt/ß-catenin pathway was activated, indicating their role in promoting hair growth. ASC-Exosomes also promoted hair shaft elongation and ALP activity, suggesting a potential for hair regeneration. Thirty participants with AGA enrolled and treated over 24 weeks. The subjects experienced a significant increase in total hair density, improved global photographic assessments, and reported higher subjective satisfaction without severe adverse reactions. CONCLUSION: This research contributes to the growing body of evidence supporting the use of exosomes in hair loss treatment, offering a safe and effective alternative for individuals with AGA.
Assuntos
Tecido Adiposo , Alopecia , Proliferação de Células , Exossomos , Folículo Piloso , Fator 1 de Ligação ao Facilitador Linfoide , Regeneração , Humanos , Alopecia/terapia , Folículo Piloso/citologia , Exossomos/metabolismo , Adulto , Masculino , Feminino , Tecido Adiposo/citologia , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , beta Catenina/metabolismo , Via de Sinalização Wnt , Pessoa de Meia-Idade , Cabelo/crescimento & desenvolvimento , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Células Cultivadas , Resultado do TratamentoRESUMO
Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.
Assuntos
Folículo Piloso , Hidroxiprostaglandina Desidrogenases , Humanos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Hidroxiprostaglandina Desidrogenases/metabolismo , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Derme/metabolismo , Derme/citologia , Derme/efeitos dos fármacos , Células Cultivadas , Via de Sinalização Wnt/efeitos dos fármacos , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Cicatrização/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Inibidores Enzimáticos/farmacologiaRESUMO
While many gene expression studies have focused on male pattern baldness (MPB), few studies have investigated the genetic differences between bald and non-bald hair follicles in female pattern hair loss (FPHL). This study aimed to identify molecular biomarkers associated with FPHL through genetic analysis of paired bald and non-bald hair follicles from 18 FPHL patients, using next-generation sequencing (NGS) techniques. RNA transcriptome analysis was performed to identify differentially expressed genes (DEGs) between bald and non-bald hair follicles in FPHL. The DEGs were validated using real-time PCR, and protein expression was confirmed through immunohistochemistry and western blot analysis. Our findings suggest that HOXB13, SFRP2, PTGDS, CXCR3, SFRP4, SOD3, and DCN are significantly upregulated in bald hair follicles compared to non-bald hair follicles in FPHL. SFRP2 and PTGDS were found to be consistently highly expressed in bald hair follicles in all 18 samples. Additionally, elevated protein levels of SFRP2 and PTGDS were confirmed through western blot and immunohistochemical analysis. Our study identified SFRP2 and PTGDS as potential biomarkers for FPHL and suggests that they may play a role in inducing hair loss in this condition. These findings provide a foundation for further research on the pathogenesis of FPHL and potential therapeutic targets.
Assuntos
Alopecia , Povo Asiático , Perfilação da Expressão Gênica , Folículo Piloso , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Alopecia/genética , Alopecia/patologia , Povo Asiático/genética , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas , Couro Cabeludo/patologia , TranscriptomaRESUMO
The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors-such as bFGF, KGF, PDGF-AA, and VEGF-were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Cabelo/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Sistema de Sinalização das MAP Quinases , Quercetina/análogos & derivados , Apoptose/efeitos dos fármacos , Butadienos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Derme/citologia , Metabolismo Energético/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quercetina/química , Quercetina/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismoRESUMO
Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ß-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.
RESUMO
BACKGROUND: Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. METHODS: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. RESULTS: We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. CONCLUSION: These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.
Assuntos
Angelica/química , Anti-Inflamatórios/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Dinitroclorobenzeno/toxicidade , Lithospermum/química , Extratos Vegetais/administração & dosagem , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/genética , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The present study aimed to investigate the antiinflammatory effect and mechanism of action of isosecotanapartholide (ISTP), isolated from Artemisia princeps Pampanini extract (APE). The effects of ISTP and APE on the proliferation of human keratinocytes following stimulation by tumor necrosis factorα/interferonγ were assessed. ISTP and APE downregulated the expression levels of signal transducer and activator of transcription1 (STAT1), and reduced interleukin33 (IL33) production. ISTP and APE inhibited the mRNA expression levels of thymus and activationregulated chemokine (TARC/CCL17) in a dosedependent manner. Western blot analysis demonstrated that ISTP and APE dosedependently inhibited protein expression levels of intercellular adhesion molecule1 and phosphorylation of STAT1. The results of the present study indicate that ISTP may inhibit TARC/CCL17 production in human epidermal keratinocytes via the STAT1 signaling pathway and may be associated with the inhibition of IL33 production. The current study indicated that ISTP is an active component in APE and may be a potential therapeutic agent for the treatment of inflammatory skin disorders.
Assuntos
Artemisia/química , Interleucina-33/biossíntese , Queratinócitos/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Humanos , Queratinócitos/citologia , Extratos Vegetais/químicaRESUMO
BACKGROUND: Skin hyperpigmentary disorders including postinflammatory hyperpigmentation, melasma, solar lentigines, and conditions like freckles are common. The light-emitting diodes (LEDs) are the latest category of nonthermal and noninvasive phototherapy to be considered in skin pigmentation disorder treatment. PURPOSE: The purpose of this study was to investigate the effects of 660-nm LED on inhibition of melanogenesis. We investigated whether a 660-nm LED affected melanin synthesis in in vitro and in vivo models, and we explored the mechanisms involved. METHODS: The inhibitory effect of 660-nm LED on melanin synthesis was evaluated in B16F10 cells and HRM-2 melanin-possessing hairless mice were used to evaluate the antimelanogenic effects of 660-nm LED. RESULTS: Interestingly, 660-nm LED inhibited alpha-melanocyte-stimulating hormone-induced tyrosinase activity in B16F10 cells. We also found that 660-nm LED decreased MITF and tyrosinase expression and induced the activation of ERK. These findings suggest that the depigmenting effects of 660-nm LED result from downregulation of MITF and tyrosinase expression due to increased ERK activity. The 660-nm LED reduced UVB-induced melanogenesis in the skin of HRM-2 via downregulation of tyrosinase and MITF. CONCLUSION: These findings suggest 660-nm LED is a potentially depigmentation strategy.
Assuntos
Luz , Melaninas/biossíntese , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Biossíntese de Proteínas/efeitos da radiação , Pele/efeitos da radiação , Animais , Linhagem Celular Tumoral , Oxirredutases Intramoleculares/metabolismo , Antígeno MART-1/análise , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Pelados , Fator de Transcrição Associado à Microftalmia/análise , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Monofenol Mono-Oxigenase/análise , Oxirredutases/metabolismo , Proteínas S100/análise , Pele/química , alfa-MSH/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a common inflammatory skin disease that can affect all age groups. It has a relapsing course, which dramatically affects the quality of life of patients. A 308-nm excimer laser has been reported to be a safe and effective treatment for inflammatory skin diseases, although the range of potential application has not been fully explored. The purpose of this study was to evaluate the therapeutic effects of a 308-nm laser on AD-like skin lesions in NC/Nga mice. STUDY DESIGN/MATERIALS AND METHODS: Dermatophagoides farinae-exposed NC/Nga mice with a clinical score of 12 were treated with either a 308-nm excimer laser or narrowband-UVB (NB-UVB). The effects of the 308-nm excimer laser were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, including IgE and Th2-mediated cytokines. RESULTS: The 308-nm excimer laser significantly reduced the severity of skin lesions and decreased the total serum levels of IgE and Th2-mediated cytokines. The excimer laser also significantly reduced the inflammatory cellular infiltrate into AD-induced skin lesions. Moreover, treatment with the 308-nm excimer laser led to recovery of skin barrier function in AD-induced skin lesions. CONCLUSION: The 308-nm excimer laser can be considered a valid and safe therapeutic option for the treatment of localized AD. Lasers Surg. Med. 48:629-637, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Dermatite Atópica/cirurgia , Lasers de Excimer/uso terapêutico , Animais , Biomarcadores/sangue , Citocinas/sangue , Dermatite Atópica/sangue , Dermatite Atópica/patologia , Masculino , Camundongos , Resultado do TratamentoRESUMO
Allergic rhinitis (AR) is an allergic inflammation of the nasal airways. The Korean herbal medicine, So-Cheong-Ryong-Tang (SCRT) has been typically used for the treatment of AR for hundreds of years. In the present study, we investigated whether SCRT suppresses the progression of AR in animal model. AR was induced by ovalbumin (OVA). Treatment with SCRT was assessed to study the effect of SCRT on AR in mice. Histological analysis, multiplex cytokine assay, blood analysis, cell viability assay, RT-PCR and Elisa assay were performed to verify inhibitory effect of SCRT on AR. SCRT reduced infiltration of inflammatory cells into nasal cavity. SCRT reduced infiltration of mast cells into nasal mucosa. SCRT reduced the levels of cytokines (IL-4 and LIF) in the serum. SCRT reduced the levels of leukocytes in the blood. SCRT decreased cell viability of HMC-1 cells and splenocyte. SCRT suppressed IL-4 level in HMC-1 cells and splenocyte cells in a dose-dependent manner. SCRT suppressed IL-6 level and TNF-α level in splenocyte. SCRT suppresses the progression of AR induced by OVA. SCRT might be a useful drug for the treatment of AR.
Assuntos
Antialérgicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Rinite Alérgica/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-4/sangue , Interleucina-6/metabolismo , Fator Inibidor de Leucemia/sangue , Leucócitos/metabolismo , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Mucosa Nasal/metabolismo , Ovalbumina/efeitos adversos , Fitoterapia , Rinite Alérgica/etiologia , Baço/citologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. AIMS: To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. METHODS: We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. RESULTS: MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. CONCLUSION: These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage.
Assuntos
Células-Tronco Mesenquimais , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Administração Cutânea , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Meios de Cultivo Condicionados/farmacologia , Tecido Elástico/efeitos dos fármacos , Tecido Elástico/patologia , Tecido Elástico/efeitos da radiação , Feminino , Fibroblastos , Humanos , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Camundongos Pelados , Pró-Colágeno/biossíntese , Pele/efeitos da radiação , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVES: Ultraviolet light-emitting diodes (UV-LEDs) are a novel light source for phototherapy. This research investigated the in vitro safety and efficacy of UV-LEDs as a phototherapeutic device for atopic dermatitis (AD). STUDY DESIGN/MATERIALS AND METHODS: Human keratinocytes and fibroblasts were irradiated by UV-LEDs with a center wavelength of 310 and 340 nm. We examined the effects of UV-LED irradiation on the suppression of TNF-α/IFN-γ-induced activation of STAT1 and ICAM-1 and on NF-κB expression; we used the following methods: cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunocytochemistry. RESULTS: We observed anti-inflammatory responses through the suppression of TNF-α/IFN-γ-induced expression of TARC and MCP-1/CCL2, IL-1beta, IL-6, and sICAM-1 via blockage of ICAM-1 activation and subsequent activation of STAT1 and NF-κB. The results suggested that UV-LED irradiation inhibited ICAM expression by suppressing TNF-α/IFN-γ-induced NF-κB activation in vitro. CONCLUSION: We concluded that novel UV-LED (310 and 340 nm) modalities were effective for the treatment of AD and may be promising for the treatment of inflammatory skin diseases.
Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Interferon gama/metabolismo , Queratinócitos/efeitos da radiação , Fosforilação/efeitos da radiação , Fator de Transcrição STAT1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Biomarcadores/metabolismo , Western Blotting , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Imuno-Histoquímica , Queratinócitos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Terapia Ultravioleta/instrumentaçãoRESUMO
Breast cancer is the most common cancer for women and is a major cause of mortality in women. Doxorubicin is a generally used chemotherapy drug for breast cancer. However, multidrug resistance of breast cancer interferes with the chemotherapy. We examined whether cucurbitacin D affects doxorubicin resistance of MCF7/ADR breast cancer cells. Cell viability was measured by MTT assay. Levels of p-STAT3, p-NF-κB, IκB, and caspases were measured by Western blot analysis. Nuclear staining of Stat3 and NF-κB was measured by immunocytochemistry. STAT3 and NF-κB transcriptional activity was detected by STAT3 and NF-κB luciferase reporter gene assays. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by Annexin V-FITC/propidium iodide assay. More than 90% of MCF7/ADR cells lived upon treatment with doxorubicin for 24 h. However, upon treatment with cucurbitacin D, cell death was more than 60%. Co-administration of cucurbitacin D and doxorubicin induced apoptosis, and G2/M cell cycle arrest, and inhibited upregulated Stat3 by doxorubicin on MCF7/ADR cells. Additionally, cucurbitacin D led to an increase in the IκBα level in the cytosol and a decrease in the p-NF-κB level in the nucleus. Finally, cucurbitacin D inhibited translocation of Stat3 and NF-κB and decreased transcriptional activity in the nucleus. Cucurbitacin D decreases cell proliferation and induces apoptosis by inhibiting Stat3 and NF-κB signaling in doxorubicin-resistant breast cancer cells. Cucurbitacin D could be used as a useful compound to treat adriamycin-resistant patients.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Triterpenos/farmacologia , Neoplasias da Mama/patologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/metabolismo , Células MCF-7 , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Allergic rhinitis (AR) is an allergic inflammation of the nasal airways. The prevalence of AR is increasing worldwide. We investigated whether Hyeonggaeyeongyo-tang (HYT) is effective to suppress the progression of AR induced by ovalbumin (OVA). Male BALB/c mice were used for this study. Allergic rhinitis was induced by OVA. Treatment with HYT was assessed to study the effect of HYT on allergic rhinitis in mice. Histological analysis, immunohistochemistry, multiplex cytokine assay, blood analysis, and cell viability assay were performed to verify inhibitory effect of HYT on allergic rhinitis. HYT did not show any toxicity maintaining body weight. Food intake was steady without variation in mice. HYT reduced infiltration of inflammatory cells and mast cells into nasal cavity. HYT reduced the levels of cytokines and leukocytes in the blood. HYT decreased the splenocyte cell viability. Antihistamines and steroids are the most common medications used to treat allergic rhinitis. However, long-term use of drug generates resistance or side effects requiring the development of new drug. Our present study clearly demonstrates that HYT suppresses the progression of allergic rhinitis induced by OVA. This suggests that HYT might be a useful drug for the treatment of allergic rhinitis.
Assuntos
Antialérgicos/uso terapêutico , Ovalbumina/farmacologia , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ingestão de Alimentos/efeitos dos fármacos , Imuno-Histoquímica , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Camundongos , Mucosa Nasal/citologiaRESUMO
CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.
Assuntos
Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Dermatite Atópica/metabolismo , Derme/efeitos dos fármacos , Derme/metabolismo , Dinitroclorobenzeno/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Imunoglobulina E/sangue , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real , Células Th2/metabolismoRESUMO
The objective of the present study was to analyze the effect of a mixture of medicinal plants [Angelica gigas Nakai, Panax ginseng and Rhus verniciflua Stokes (APR)] on lipopolysaccharide (LPS)-induced inflammatory responses in the murine macrophage cell line RAW264.7. Cells were treated with APR and LPS at various concentrations and indicated times. WST assay, trypan blue assay and quantification of activated cells demonstrated that APR suppressed cell proliferation in a dose-dependent manner. APR induced G1 cell cycle arrest and inhibited the LPS-induced phosphorylation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (p38) and necrosis factor κB (NF-κB). APR also suppressed nitric oxide synthase isoform (iNOS) and prostaglandin endoperoxide synthase 2 (Cox-2) messenger ribonucleic acid (mRNA) expression induced by LPS. Furthermore, APR decreased LPS-induced intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential, as well as induced PARP and caspase-3 cleavage, suggesting that APR causes apoptosis. In conclusion, the present study indicated that APR may be advantageous in treating inflammatory disease.
Assuntos
Anti-Inflamatórios/farmacologia , Medicina Herbária , Macrófagos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismoRESUMO
Inflammatory response is a major defense mechanism against pathogens and chemical or mechanical injury. Rhus verniciflua Stokes (RVS) has traditionally been used as an ingredient in East Asian medicine for the treatment of gastritis, stomach cancer and atherosclerosis. The aim of the current study was to analyze the effect of RVS on LPSinduced inflammatory responses in the RAW264.7 mouse macrophage cell line. RAW264.7 cells were treated with various concentrations of RVS and LPS at specific time points. WST assay, trypan blue assay and quantification of activated cells revealed that RVS suppressed cell proliferation in a dosedependent manner. RVS induced G1 cell cycle arrest, suppressed iNOS and COX2 mRNA expression induced by LPS and decreased intracellular ROS levels induced by LPS. In addition, RVS induced PARP and caspase3 cleavage suggesting that RVS causes cell death. Results of the present study indicate that RVS may be advantageous in treating inflammatory disease.
Assuntos
Anti-Inflamatórios/química , Extratos Vegetais/química , Rhus/química , Animais , Anti-Inflamatórios/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional do Leste Asiático , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rhus/metabolismoRESUMO
Trichosanthes kirilowii tuber is a traditional medicine which exhibits various medicinal effects including antidiabetic and anticancer activities in several cancer cells. Recently, it was reported that Cucurbitacin D (CuD) isolated from Trichosanthes kirilowii also induces apoptosis in several cancer cells. Constitutive signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor, is often observed in many human malignant tumor, including breast cancer. In the present study, we tested whether Trichosanthes kirilowii ethanol extract (TKE) or CuD suppresses cell growth and induces apoptosis through inhibition of STAT3 activity in breast cancer cells. We found that both TKE and CuD suppressed proliferation and induced apoptosis and G2/M cell cycle arrest in MDA-MB-231 breast cancer cells by inhibiting STAT3 phosphorylation. In addition, both TKE and CuD inhibited nuclear translocation and transcriptional activity of STAT3. Taken together, our results indicate that TKE and its derived compound, CuD, could be potent therapeutic agents for breast cancer, blocking tumor cell proliferation and inducing apoptosis through suppression of STAT3 activity.
RESUMO
Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG) prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF) that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS) and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO) synthesis and secretions of cytokines including IL-6 and TNF- α . Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, I κ B α , and NF- κ B in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia.
RESUMO
Our study investigated whether the extract of six herbal medicines (OB-1) has an inhibitory effect on obesity. High-fat diet-(HFD-) induced rats and controls were treated with 40 mg/100 g body weight of OB-1 or saline once a day for 5 weeks. After significant changes in body weight were induced, OB-1 and saline were administered to each subgroup of HFD and control groups for additional 5 weeks. No statistically significant decrease of body weight in OB-1-treated rats was found compared to controls. However, OB-1-treated rats were found to be more active in an open-field test and have a reduction in the size of adipocytes compared to controls. We observed no changes in the mRNA expressions of leptin and adiponectin from adipocytes between OB-1- and saline-treated rats with HFD-induced obesity group. However, OB-1 treatments were shown to be inversely correlated with accumulation of lipid droplets in liver tissue, suggesting that OB-1 could inhibit a lipid accumulation by blocking the pathway related to lipid metabolism. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) was significantly increased in OB-1-treated rats with HFD compared to controls. These results suggest that OB-1 has no direct antiobesity effect and, however, could be a regulator of cellular metabolism.