RESUMO
Background: The root of Saposhnikovia divaricata (Turcz.) Schischk is a well-known traditional medicinal plant, containing various bioactive compounds with anti-inflammatory, antioxidant, and analgesic properties. However, no scientific studies have validated its clinical use as an anti-inflammatory agent against inflammatory bowel disease (IBD). This study aimed to investigate whether the root extract of S. divaricata ameliorates IBD and induces gut microbial alteration, using a RAW 264.7 cell line and a DSS-induced colitis mouse model. Methods: To investigate the anti-inflammatory effects and alleviation of IBD, using a methanol extract of Saposhnikovia divaricata (Turcz.) Schischk. root (MESD), RAW 264.7, murine macrophages and a dextran sodium sulfate (DSS)-induced colitis mouse model were employed. 16S rRNA gene sequencing was conducted to determine the alterations in the gut microbiota of mice with DSS-induced colitis. Results: MESD significantly decreased nitric oxide (NO) and inflammatory cytokine levels in lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro. Oral administration of MESD reduced the expression of inflammatory cytokines in the colons of mice with DSS-induced colitis. Additionally, MESD inhibited the abundance of Clostridium sensu stricto 1 and enhanced the predicted functional pathways, including l-glutamate degradation VIII (to propanoic acid). Seven compounds with anti-inflammatory properties were isolated from the MESD. Among them, 3'-O-acetylhamaudol and 3'-O-angeloylhamaudol exhibited strong anti-inflammatory effects in vitro. Conclusion: Overall, MESD may be a potential natural product for the treatment of IBD by lowering inflammatory cytokine levels and altering gut microbiota composition.
RESUMO
BACKGROUND: Nonalcoholic steatohepatitis (NASH), a liver disease caused by a nonalcoholic fatty liver, is increasing in incidence worldwide. Owing to the complexity of its pathogenic mechanisms, there are no therapeutic agents for this disease yet. The ideal drug for NASH needs to concurrently decrease hepatic lipid accumulation and exert anti-inflammatory, antifibrotic, and antioxidative effects in the liver. Because of their multipurpose therapeutic effects, we considered that medicinal herbs are suitable for treating patients with NASH. METHODS: We determined the efficacy of the alcoholic extract of Lysimachia vulgaris var. davurica (LV), an edible medicinal herb, for NASH treatment. For inducing NASH, C57BLKS/J lar-Leprdb/Leprdb (db/db) male mice were fed with a methionine-choline deficient (MCD) diet ad libitum. After 3 weeks, the LV extract and a positive control (GFT505) were administered to mice by oral gavage for 3 weeks with a continued MCD diet as needed. RESULTS: In mice with diet-induced NASH, the LV extract could relieve the disease symptoms; that is, the extract ameliorated hepatic lipid accumulation and also showed antioxidative and anti-inflammatory effects. The LV extract also activated nuclear factor E2-related factor 2 (Nrf2) expression, leading to the upregulation of antioxidants and detoxification signaling. Moreover, the extract presented remarkable efficacy in alleviating liver fibrosis compared with GFT505. This difference was caused by significant LV extract-mediated reduction in the mRNA expression of fibrotic genes like the alpha-smooth muscle actin and collagen type 3 alpha 1. Reduction of fibrotic genes may thus relate with the downregulation of transforming growth factor beta (TGFß)/Smad signaling by LV extract administration. CONCLUSIONS: Lipid accumulation and inflammatory responses in the liver were alleviated by feeding LV extract to NASH-induced mice. Moreover, the LV extract strongly prevented liver fibrosis by blocking TGFß/Smad signaling. Hence, LV showed sufficient potency for use as a therapeutic agent against NASH.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Primulaceae/química , Actinas/genética , Actinas/metabolismo , Animais , Colina/análise , Colina/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Dieta , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Metionina/análise , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Exposure to Ultraviolet (UV) light induces photoaging of skin, leading to wrinkles and sunburn. The perennial herb Humulus japonicus, widely distributed in Asia, is known to have antiinflammatory, antimicrobial, and antioxidant effects. However, the physiological activities of isolated compounds from H. japonicus have rarely been investigated. This study focused on the isolation of active compounds from H. japonicus and the evaluation of their effects on photoaging in UVB-irradiated human fibroblast (Hs68) cells. When the extract and four fractions of H. japonicus were treated respectively in UVB-irradiated Hs68 cells to investigate anti-photoaging effects, the ethyl acetate (EtOAc) fraction showed the strongest inhibitory effect on MMP- 1 secretion. From EtOAc fraction, we isolated luteolin-8-C-glucoside (1), apigenin-8-C-glucoside (2), and luteolin-7-O-glucoside (3). These compounds suppressed UVB-induced MMP-1 production by inhibiting the phosphorylation of the mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1). When the antioxidant activity of the compounds were estimated by conducting western blot, calculating the bond dissociation energies of the O-H bond (BDE) at different grade, and measuring radical scavenging activity, we found luteolin-8-C-glucoside (1) showed the strongest activity on the suppression of UVB-induced photoaging. These results demonstrate the inhibitory effect of three flavone glycosides derived from H. japonicus on MMP-1 production, MAPK and AP-1 signaling, and oxidative stress; this could prove useful in suppressing UVB induced photoaging. [BMB Reports 2020; 53(7): 379-384].
Assuntos
Fibroblastos/metabolismo , Humulus/metabolismo , Extratos Vegetais/farmacologia , Acetatos/química , Anti-Inflamatórios/farmacologia , Apigenina/química , Apigenina/farmacologia , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Flavonas/química , Flavonas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Humulus/química , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
Nonalcoholic fatty liver disease (NAFLD) ranges in severity from hepatic steatosis to cirrhosis. Lemon balm and its major constituent, rosmarinic acid (RA), effectively improve the liver injury and obesity; however, their therapeutic effects on nonalcoholic steatohepatitis (NASH) are unknown. In this study, we investigated the effects of RA and a lemon balm extract (LBE) on NAFLD and liver fibrosis and elucidated their mechanisms. Palmitic acid (PA)-exposed HepG2 cells and db/db mice fed a methionine- and choline-deficient (MCD) diet were utilized to exhibit symptoms of human NASH. LBE and RA treatments alleviated the oxidative stress by increasing antioxidant enzymes and modulated lipid metabolism-related gene expression by the activation of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis and inflammation in vitro and in vivo. Together, LBE and RA could improve liver damage by non-alcoholic lipid accumulation and may be promising medications to treat NASH.
Assuntos
Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Melissa/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Cinamatos/isolamento & purificação , Cinamatos/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido RosmarínicoRESUMO
The liver X receptors (LXRs) are major regulators of lipogenesis, and their reduced activation by an inhibitor could be a treatment strategy for fatty liver disease. Small molecules originating from dietary food are considered suitable and attractive drug candidates for humans in terms of safety. In this study, an edible plant, Lysimachia vulgaris (LV), used as a traditional and medicinal food in East Asia was evaluated for lipogenesis decreasing effects. Activity-guided fractionation was performed, and the isolated compounds were identified using spectroscopic methods. We conducted in vitro real-time polymerase chain reaction (PCR) and Western blotting as well as histological and biochemical analyses following in vivo treatments. Using a high-fat diet animal model, we confirmed that LV extracts (LVE) decreased lipogenic metabolism and restored liver function to control levels. To identify active components, we conducted activity-guided fractionation and then isolated compounds. Two compounds, loliolide and pinoresinol, were identified in the dichloromethane fraction, and they significantly attenuated the expression levels of lipogenic factors including sterol regulatory element-binding protein (SREBP)-1, stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Importantly, loliolide and pinoresinol significantly accelerated the protein degradation of LXRs by enhanced ubiquitination, which inhibited lipogenesis. These results suggest that loliolide and pinoresinol might be potential candidate supplementary treatments for nonalcoholic fatty liver disease (NAFLD) by reducing lipogenesis through increased ubiquitination of LXRs.
Assuntos
Benzofuranos/administração & dosagem , Furanos/administração & dosagem , Lignanas/administração & dosagem , Lipogênese/efeitos dos fármacos , Receptores X do Fígado/metabolismo , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Primulaceae/química , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Humanos , Fígado/metabolismo , Receptores X do Fígado/genética , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismoRESUMO
Pterocarpus santalinus has been traditionally used as a medicinal plant owing to its anti-inflammatory, anthelmintic, tonic, antihyperglycemic, and diaphoretic properties. We hypothesized that P. santalinus might have therapeutic potential in alleviating allergy and atopic dermatitis. Thus, we investigated the inhibitory effects of P. santalinus extract against allergic responses and 2,4-dinitrochlorobenzene-induced atopic dermatitis-like dorsal skin lesions using immunoglobulin E-sensitized rat basophilic leukemia-2H3 mast cells and NC/Nga mice. Degranulation and enzyme-linked immunosorbent assays were conducted to measure degranulation, proinflammatory cytokine levels, and prostaglandin E2 concentrations in immunoglobulin E/antigen-sensitized RBL-2H3 mast cells. The therapeutic efficacy of P. santalinus extract in 2,4-dinitrochlorobenzene-induced atopic dermatitis was evaluated through morphological, physiological, and immunological analysis. P. santalinus extract inhibited ß-hexosaminidase and histamine release and reduced tumor necrosis factor-α, interleukin-4, and prostaglandin E2 secretion. Furthermore, P. santalinus extract suppressed atopic dermatitis-like skin lesions by regulating the serum levels of immunoglobulin E and immunoglobulin G2a, and messenger ribonucleic acid expression of T helper cell 1- and T helper cell 2-related mediators in the skin lesions. Histopathological analyses showed a decrease in epidermal thickness and intradermal inflammatory cell infiltration. These results suggested that P. santalinus extract might have beneficial effects in treating allergic and atopic dermatitis-like skin disorders.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Mastócitos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Pterocarpus/química , Animais , Linhagem Celular , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Dinitrofluorbenzeno , Feminino , Imunoglobulina E/sangue , Imunoglobulina G , Mastócitos/imunologia , Camundongos , RatosRESUMO
Genistein, a phyto-estrogen, can potentially replace endogenous estrogens in postmenopausal women, but the underlying molecular mechanisms remain incompletely understood. To obtain insight into the effect of genistein on bone differentiation, RNA sequencing (RNA-seq) analysis was used to detect differentially expressed genes (DEGs) in genistein-treated vs. untreated MC3T3-E1 mouse osteoblastic cells. Osteoblastic cell differentiation was monitored by measuring osteoblast differentiation factors (ALP production, bone mineralization, and expression of osteoblast differentiation markers). From RNA-seq analysis, a total of 132 DEGs (including 52 up-regulated and 80 down-regulated genes) were identified in genistein-treated cells (FDR q-value < 0.05 and fold change > 1.5). KEGG pathway and Gene Ontology (GO) enrichment analyses were performed to estimate the biological functions of DEGs and demonstrated that these DEGs were highly enriched in functions related to chemotactic cytokines. The functional relevance of DEGs to genistein-induced osteoblastic cell differentiation was further evaluated by siRNA-mediated knockdown in MC3T3-E1 cells. These siRNA knockdown experiments (of the DEGs validated by real-time qPCR) demonstrated that two up-regulated genes (Ereg and Efcab2) enhance osteoblastic cell differentiation, while three down-regulated genes (Hrc, Gli, and Ifitm5) suppress the differentiation. These results imply their major functional roles in bone differentiation regulated by genistein.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Genisteína/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Fitoestrógenos/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Camundongos , Análise de Sequência de RNARESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Achillea asiatica Serg. is a perennial herb belonging to the Asteraceae family that has long been traditionally used to treat acute intestinal and stomach inflammation, persistent fever, ulcers, wounds, and rheumatism. AIM OF THE STUDY: We investigated the effect of A. asiatica extract (AAE) on cutaneous wound healing. MATERIALS AND METHODS: To assess the effect of AAE on wounds, an incisional Sprague-Dawley (SD) rat model was topically treated with AAE for 2 weeks. HaCaT keratinocytes, Hs68 dermal fibroblasts, and RAW 264.7 macrophages were used for in vitro experiments. After treatment with AAE, cell viability, cell migration, and production of nitric oxide (NO) and prostaglandin E2 (PGE2) were investigated. mRNA expression of collagen type I and III and inflammatory cytokines was measured by RT-PCR. The effect of AAE on activation of ß-catenin and other markers was determined by Western blot analysis. RESULTS: AAE treatment significantly increased epithelialization and accelerated wound healing in SD rats. Meanwhile, AAE and its active compounds reduced NO and PGE2 release and mRNA expression of inflammatory cytokines in RAW 264.7 macrophages, reflecting anti-inflammatory activity. Furthermore, AAE and its constituents stimulated collagen expression in Hs68 fibroblasts by activating transforming growth factor-ß and stimulated keratinocyte differentiation and motility by inducing ß-catenin, Akt, and keratinocyte differentiation markers. CONCLUSIONS: AAE improves skin wounds in SD rats and supports keratinocyte development.
Assuntos
Achillea/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Humanos , Camundongos , Ratos , Ratos Sprague-Dawley , Pele/citologia , Espectrofotometria UltravioletaRESUMO
Stellera chamaejasme L. (Thymelaeaceae) is a perennial herb that is widely used in traditional Chinese medicine to treat tumours, tuberculosis and psoriasis. S. chamaejasme extract (SCE) possesses anti-inflammatory, analgesic and wound healing activities; however, the effect of S. chamaejasme and its active compounds on cutaneous wound healing has not been investigated. We assessed full-thickness wounds of Sprague-Dawley (SD) rats and topically applied SCE for 2 weeks. In vitro studies were performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW 264.7 macrophages to determine cell viability (MTT assay), cell migration, collagen expression, nitric oxide (NO) production, prostaglandin E2 (PGE2) production, inflammatory cytokine expression and ß-catenin activation. In vivo, wound size was reduced and epithelisation was improved in SCE-treated SD rats. In vitro, SCE and its active compounds induced keratinocyte migration by regulating the ß-catenin, extracellular signal-regulated kinase and Akt signalling pathways. Furthermore, SCE and its active compounds increased mRNA expression of type I and III collagen in Hs68 fibroblasts. SCE and chamechromone inhibited NO and PGE2 release and mRNA expression of inflammatory mediators in RAW 264.7 macrophages. SCE enhances the motility of HaCaT keratinocytes and improves cutaneous wound healing in SD rats.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Thymelaeaceae/química , Cicatrização/efeitos dos fármacos , Animais , Linhagem Celular , Cromatografia Líquida , Colágeno/genética , Colágeno/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Estrutura Molecular , Proteína Oncogênica v-akt/metabolismo , Ratos , Pele/metabolismo , Pele/patologiaRESUMO
SCOPE: Nonalcoholic fatty liver diseases (NAFLD) range histopathologically from hepatic steatosis to steatohepatitis. Chicoric acid has beneficial effects on obesity and liver injury, but its effects on nonalcoholic steatohepatitis (NASH) have not yet been determined. This study examined the effects of Crepidiastrum denticulatum extract (CDE) and its active compound chicoric acid in a mouse model of NASH and fibrosis. METHODS: CDE and chicoric acid were orally administrated to mice fed a methionine- and choline-deficient (MCD) diet. HepG2 and AML-12 cells in MCD medium were incubated with chicoric acid. MCD-fed mice developed the histopathological characteristics of human NASH, including altered regulation of lipid metabolism, inflammation, fibrosis, and oxidation-associated expression, along with augmented lipoperoxidation. Administration of CDE or chicoric acid to MCD-fed mice and HepG2 and AML-12 cells in MCD medium reduced oxidative stress by upregulating antioxidant enzymes and decreased inflammation by inhibiting proinflammatory cytokines and nuclear factor-κB activation. In addition, CDE or chicoric acid reduced fibrosis, apoptosis, and lipogenesis-related gene expression and increased AMP Kinase activation both in vivo and in vitro. CONCLUSIONS: CDE and chicoric acid may be effective in the treatment of NAFLD and NASH.
Assuntos
Ácidos Cafeicos/farmacologia , Deficiência de Colina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Succinatos/farmacologia , Animais , Asteraceae/química , Linhagem Celular , Modelos Animais de Doenças , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Cirrose Hepática/sangue , Masculino , Metionina/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVES: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells. METHODS: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically. KEY FINDINGS: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells. CONCLUSION: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.
Assuntos
Anti-Inflamatórios/farmacologia , Quimiocinas/metabolismo , Dermatite Atópica/prevenção & controle , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhamnaceae/química , Pele/efeitos dos fármacos , Ácido Vanílico/análogos & derivados , Ácido Vanílico/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Quimiocina CCL17/metabolismo , Quimiocina CCL22/metabolismo , Quimiocinas/sangue , Quimiocinas/imunologia , Dermatite Atópica/sangue , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interferon gama/farmacologia , Queratinócitos/imunologia , Queratinócitos/metabolismo , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Pele/patologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Ácido Vanílico/isolamento & purificaçãoRESUMO
The aim of our study is to investigate the molecular mechanism of gomisin J from Schisandra chinensis on the oleic acid (OA)-induced lipid accumulation in HepG2 cells. Gomisin J attenuated lipid accumulation in OA-induced HepG2 cells. It also suppressed the expression of lipogenic enzymes and inflammatory mediators and increased the expression of lipolytic enzymes in OA-induced HepG2 cells. Furthermore, the use of specific inhibitors and fetuin-A siRNA and liver kinase B1 (LKB1) siRNA transfected cells demonstrated that gomisin J regulated lipogenesis and lipolysis via inhibition of fetuin-A and activation of an AMP-activated protein kinase (AMPK)-dependent pathway in HepG2 cells. Our results showed that gomisin J suppressed lipid accumulation by regulating the expression of lipogenic and lipolytic enzymes and inflammatory molecules through activation of AMPK, LKB1, and Ca(2+)/calmodulin-dependent protein kinase II and inhibition of fetuin-A in HepG2 cells. This suggested that gomisin J has potential benefits in treating nonalcoholic fatty liver disease.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lignanas/farmacologia , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ácido Oleico/metabolismo , Extratos Vegetais/farmacologia , Compostos Policíclicos/farmacologia , Schisandra/química , alfa-2-Glicoproteína-HS/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/enzimologia , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , alfa-2-Glicoproteína-HS/genéticaRESUMO
Cassia tora seed is widely used due to its various biological properties including anticancer, antidiabetic, and anti-inflammatory effects. However, there has been no report of the effects of C. tora seed extract (CTE) on immunoglobulin E (IgE)-mediated allergic responses. In this research, we demonstrated the effects of CTE and its active compound aurantio-obtusin on IgE-sensitized allergic reactions in mast cells and passive cutaneous anaphylaxis (PCA). CTE and aurantio-obtusin suppressed degranulation, histamine production, and reactive oxygen species generation and inhibited the production and mRNA expression of tumor necrosis factor-α and interleukin-4. CTE and aurantio-obtusin also suppressed the prostaglandin E2 production and expression of cyclooxygenase 2. Furthermore, CTE and aurantio-obtusin suppressed IgE-mediated FcεRI signaling such as phosphorylation of Syk, protein kinase Cµ, phospholipase Cγ, and extracellular signal-regulated kinases. CTE and aurantio-obtusin blocked mast cell-dependent PCA in IgE-mediated mice. These results suggest that CTE and aurantio-obtusin are a beneficial treatment for allergy-related diseases.
Assuntos
Anafilaxia/tratamento farmacológico , Antraquinonas/administração & dosagem , Antialérgicos/administração & dosagem , Cassia/química , Imunoglobulina E/imunologia , Mastócitos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Anafilaxia/imunologia , Animais , Humanos , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Anafilaxia Cutânea Passiva , Sementes/químicaRESUMO
This study investigated the effects of youngiaside A (YA), youngiaside C (YC), and Youngia denticulatum extract (YDE) on extrinsic aging and assessed its molecular mechanisms in UVB-irradiated HaCaT keratinocytes and human dermal fibroblasts (HDFs). The results showed that YA, YC, and YDE decreased matrix metalloproteinase (MMP) expression and production in HaCaT cell and HDFs and increased collagen expression and production in HDFs. In addition, YA, YC, and YDE significantly increased antioxidant enzyme expression, thereby down-regulating UVB-induced reactive oxygen species (ROS) production and ROS-induced mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) signaling in HaCaT cells. Furthermore, YA, YC, and YDE reduced phosphorylation of IκBα and IKKα/ß, blocked nuclear factor-κB (NF-κB) p65 nuclear translocation, and strongly suppressed pro-inflammatory mediators. Finally, YA, YC, and YDE augmented UVB-induced adenosine monophosphate activated protein kinase (AMPK) phosphorylation and YA and YC did not inhibit MMP-1 production in AMPK inhibitor or nuclear factor-erythroid 2-related factor-2 (Nrf2) siRNA-treated HaCaT cells. The results suggest that these compounds could be potential therapeutic agents for prevention and treatment of skin photoaging.
Assuntos
Asteraceae/química , Fibroblastos/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Extratos Vegetais/farmacologia , Pró-Colágeno/biossíntese , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Protetores Solares/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Células Cultivadas , Colágeno Tipo I/biossíntese , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais/efeitos da radiação , Pele/enzimologia , Pele/metabolismo , Pele/efeitos da radiação , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Raios UltravioletaRESUMO
Hovenia dulcis Thunb. (Rhamnaceae) is a hardy tree native to Europe, the Middle East, and North Africa, and it is also grown in parts of Asia and has been used in traditional medicine to treat liver toxicity, stomach disorders, and inflammation. This study investigated the anti-allergy potential of an extract of the branches of H. dulcis (HDB) using the antigen-stimulated mast cell-like cell line rat basophilic leukemia (RBL)-2H3 and a passive cutaneous anaphylaxis (PCA) mouse model. Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses, and PCA were performed to measure allergic responses and proinflammatory mediators in antigen-stimulated rat basophilic leukemia (RBL)-2H3 mast cells and the PCA mouse model. In antigen-stimulated RBL-2H3 cells, HDB inhibited the secretion of ß-hexosaminidase (indicating the inhibition of degranulation) and histamine release; decreased expression and production of the inflammatory mediators, cyclooxygenase-2 and prostaglandin E2, and cytokines interleukin-4 and tumor necrosis factor-α; and suppressed activation of nuclear factor κB, a transcription factor involved in the response to cytokines. HDB attenuated phosphorylation of the mast cell downstream effectors Lyn, Syk, phospholipase Cγ, protein kinase Cµ, extracellular signal-regulated kinase and p38. In IgE-sensitized mice, HDB inhibited mast cell-dependent PCA. Furthermore, HDB contained pinosylvin and possessed significant anti-allergic activities. These results suggest that HDB would be of value in the prevention and treatment of allergic diseases.
Assuntos
Imunoglobulina E/imunologia , Mastócitos/imunologia , Anafilaxia Cutânea Passiva/imunologia , Rhamnaceae/química , Estilbenos/farmacologia , Animais , Antialérgicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/genética , Dinoprostona/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipersensibilidade/tratamento farmacológico , Interleucina-4/genética , Interleucina-4/metabolismo , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Ratos , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia anomala L. is used in Mongolian traditional medicine to treat various diseases including indigestion, abdominal pain, kidney disorders, inflammation, and female diseases. In this study we examined the effects of Paeonia anomala extract (PAE) and compounds derived from Paeonia anomala on immunoglobulin E (IgE)-mediated type I hypersensitivity responses in vitro. MATERIALS AND METHODS: Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses were performed to measure allergic and proinflammatory mediators in IgE-stimulated rat basophilic leukemia (RBL)-2H3 mast cells treated with or without PAE or gnetin H. RESULTS: Seventeen compounds were isolated, and ß-hexosaminidase release from IgE-stimulated RBL-2H3 mast cells was measured. Of the seventeen isolated compounds, gnetin H, a resveratrol derivative, significantly inhibited ß-hexosaminidase release from RBL-2H3 cells with an IC50 value of 0.3 µM. Notably, Gnetin H reduced ß-hexosaminidase release at lower concentrations than resveratrol. Furthermore, PAE and gnetin H inhibited histamine secretion, decreased the production and mRNA expression of tumor necrosis factor-α and interleukin-4 and suppressed translocation of nuclear factor κB. PAE and gnetin H also reduced the expression of cyclooxygenase-2 and production of prostaglandin E2. PAE and gnetin H suppressed the phosphorylation of Syk, protein kinase C (PKC)µ, phospholipase Cγ, and the mitogen-activated protein kinases, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. CONCLUSIONS: These results suggest that PAE and its active compound gnetin H could be promising therapeutic agents for allergic disorders.
Assuntos
Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Paeonia/química , Receptores de IgE/antagonistas & inibidores , Resorcinóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Ratos , Receptores de IgE/metabolismo , Resorcinóis/química , Resorcinóis/isolamento & purificação , Estilbenos/química , Estilbenos/isolamento & purificação , Células Tumorais CultivadasRESUMO
Aceriphyllum rossii contains an abundant source of natural flavonoids with potential antioxidant, anticancer and anti-inflammatory properties. However, the effect of A. rossii extract (ARE) on immunoglobulin E(IgE)-mediated allergic responses remains unknown. In the present study, the effects of ARE and its active compounds, quercetin and kaempferol, on IgE-mediated rat basophilic leukemia mast cell activation and passive cutaneous anaphylaxis (PCA) were investigated. ARE, quercetin, and kaempferol inhibited secretion of ß-hexosaminidase and histamine, and reduced the production and mRNA expression of interleukin-4 and tumor necrosis factor-α. ARE also decreased the production of prostaglandin E2 and leukotriene B4 and expression of cyclooxygenase 2 and 5-lipoxygenase. Furthermore, ARE, quercetin, and kaempferol inhibited IgE-mediated phosphorylation of Syk, phospholipase Cγ, protein kinase C (PKC)µ, and the mitogen-activated protein kinases, extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. ARE, quercetin, and kaempferol markedly suppressed mast cell-dependent PCA in IgE-sensitized mice. These results indicate that ARE and its active constituents, quercetin and kaempferol, may be a useful therapy for immediate-type hypersensitivity.
Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/administração & dosagem , Imunoglobulina E/imunologia , Quempferóis/administração & dosagem , Mastócitos/imunologia , Extratos Vegetais/administração & dosagem , Quercetina/administração & dosagem , Pele/imunologia , Anafilaxia/imunologia , Animais , Histamina/imunologia , Humanos , Interleucina-4/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Saxifragaceae , Pele/efeitos dos fármacosRESUMO
AIMS: Obesity develops when energy intake chronically exceeds total energy expenditure. We sought to assess whether the flavonoid-rich fraction of crude extracts from Daphne genkwa Siebold et Zuccarini (GFF) might inhibit adipogenesis of 3T3-L1 cells. MAIN METHODS: Cell viability of 3T3-L1 preadipocytes was assessed by MTT assays, and lipid accumulation was measured by Oil Red O. Adipogenesis related factors were checked by Western blot analysis. Flow cytometry was used to analyze the mitotic cell cycle during the mitotic clonal expansion phase. KEY FINDINGS: Among five flavonoids isolated from GFF, only apigenin potently inhibited the differentiation of 3T3-L1 cells. Apigenin reduced CCAAT/enhancer binding protein (C/EBP) α and peroxisome proliferator-activated receptor γ levels. Apigenin-treated 3T3-L1 cells failed to undergo clonal expansion during the early phase of adipocyte differentiation. Apigenin arrested cell cycle progression at the G0/G1 phase. This effect was associated with a marked decrease in cyclin D1 and cyclin-dependent kinase 4 expression, with the concomitant and sustained expression of p27(Kip1). In addition, apigenin inhibited the DNA-binding activity of C/EBPß in differentiating 3T3-L1 cells by down-regulating the 35kDa isoform of C/EBPß (liver-enriched activating protein) and up-regulating the expression of two different sets of C/EBP inhibitors: C/EBP homologous protein and the phospho-liver-enriched inhibitory protein isoform of C/EBPß. SIGNIFICANCE: These findings suggest that apigenin can prevent 3T3-L1 preadipocyte differentiation by the inhibition of the mitotic clonal expansion and the adipogenesis related factors and upregulation of the expression of multiple C/EBPß inhibitors.
Assuntos
Células 3T3-L1/efeitos dos fármacos , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Apigenina/farmacologia , Daphne/química , Células 3T3-L1/metabolismo , Células 3T3-L1/fisiologia , Adipogenia/fisiologia , Animais , Apigenina/isolamento & purificação , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Camundongos , PPAR gama/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
AIMS: Panduratin A isolated from Boesenbergia pandurata (Roxb.) has been reported to have antioxidant, anti-inflammatory, and anti-allergic activities. However, the effect of panduratin A on atopic dermatitis (AD) has not been studied. In the present study, we investigated the efficacy of panduratin A, an activator of peroxisome proliferator-activated receptors (PPAR) α/δ, using oxazolone-induced AD-like model in hairless mice. MAIN METHODS: To determine PPARα/δ activation of panduratin A, HaCaT, Hs68, and COS-7 cells were treated with panduratin A, then PPARα/δ and PPAR response element (PPRE) activities were assessed with a reporter gene assay. For the in vivo study, oral administration of panduratin A was performed for 4weeks, with oxazolone treatment every other day. The efficacy of panduratin A on parameters of oxazolone-induced AD was assessed physiologically, morphologically, and immunologically. KEY FINDINGS: Panduratin A increased PPARα/δ and PPRE activation both in vitro and in vivo. Panduratin A attenuated dermatitis-associated barrier damage as demonstrated by transepidermal water loss, erythema, and filaggrin expression. Furthermore, infiltration of inflammatory cells and epidermal thickness in the skin were decreased. Panduratin A decreased serum immunoglobulin (Ig) E and interleukin-4 levels but increased IgG2a and interferon-γ levels. In addition, panduratin A decreased inflammation-associated molecules in the skin. Panduratin A also decreased Th2-associated molecules and increased Th1/regulatory T cell (Treg)-associated molecules in the spleen. SIGNIFICANCE: Panduratin A showed a beneficial effect on AD by modulating Th1/Th2/Treg-associated immune response and is a potential candidate for treating AD.
Assuntos
Chalconas/farmacologia , Dermatite Atópica/prevenção & controle , Animais , Células COS , Chlorocebus aethiops , Citocinas/sangue , Citocinas/genética , Dermatite Atópica/sangue , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Proteínas Filagrinas , Genes Reporter , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Camundongos , Camundongos Pelados , Oxazolona , PPAR alfa/metabolismo , PPAR delta/metabolismo , Pele/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of ß-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment.