RESUMEN
Cancer spheroids, which mimic distinct cell-to-cell and cell-extracellular matrix interactions of solid tumors in vitro, have emerged as a promising tumor model for drug screening. However, owing to the unique characteristics of spheroids composed of three-dimensionally densely-packed cells, the precise characterizations of cell viability and function with conventional colorimetric assays are challenging. Herein, we report gold nanostructure-integrated conductive microwell arrays (GONIMA) that enable both highly efficient uniform cancer spheroid formation and precise electrochemical detection of cell viability. A nanostructured gold on indium tin oxide (ITO) substrate facilitated the initial cell aggregation and further 3D cell growth, while the non-cytophilic polymer microwell arrays restricted the size and shape of the spheroids. As a result, approximately 150 human glioblastoma spheroids were formed on a chip area of 1.13 cm2 with an average diameter of 224 µm and a size variation of only 5% (±11.36 µm). The high uniformity of cancer spheroids contributed to the stability of electrical signals measuring cell viability. Using the fabricated GONIMA, the effects of a representative chemotherapeutic agent, hydroxyurea, on the glioblastoma spheroids were precisely monitored under conditions of varying drug concentrations (0-0.3 mg/mL) and incubation times (24-48 h). Therefore, we conclude that the newly developed platform is highly useful for rapid and precise in vitro drug screening, as well as for the pharmacokinetic analyses of specific drugs using 3D cellular cancer models.
Asunto(s)
Técnicas Biosensibles , Glioblastoma , Humanos , Esferoides Celulares , Evaluación Preclínica de Medicamentos , Oro , Detección Precoz del CáncerRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is the common autoimmune disease with low quality of life. The representative treatment is medication and medication usage has improved through update of clinical guidelines, however, there are still limitations. Bee venom (BV) has been reported to have meaningful therapeutic effects and the possibility of alternative options for RA through several types of studies, but there is no well-organised and recent published systematic review (SR). METHODS: We will search randomised controlled trials about the BV on RA from the inception to 31 May 2022 in various databases, manual research and contacting authors. Electronic databases will include MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure, CiNii, J-STAGE, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Digital Science Library, Korea Institute of Science and Technology Information and Oriental Medicine Advanced Searching Integrated System. With screening and reviewing process, we will identify the eligible studies and extract the needed data. The primary outcome will be the disease activity scores indicating the improvement of RA symptoms (American College of Rheumatology response criteria 20, 50, 70), functions (Health Assessment Questionnaire, Disease Activity Score of 28 joints), joint (Western Ontario and McMaster universities osteoarthritis index), pain (Visual Analogue Scale, Numerical Rating Scale) and effective rate. The secondary outcomes will be the RA-related blood test levels and adverse events. We will perform a meta-analysis by Review Manager software, the assessment of risk of bias by Cochrane Collaboration 'risk of bias' and the determination of quality of evidence by Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: Our SR will suggest the clinical evidence of the use of BV for RA to patient, clinicians and policymakers. We will publish our results in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42021238058.
Asunto(s)
Terapia por Acupuntura , Acupuntura , Artritis Reumatoide , Venenos de Abeja , Terapia por Acupuntura/métodos , Artritis Reumatoide/tratamiento farmacológico , Venenos de Abeja/uso terapéutico , Humanos , Metaanálisis como Asunto , Calidad de Vida , Revisiones Sistemáticas como AsuntoRESUMEN
Multicellular tumor spheroids (MCTs) have been employed in biomedical fields owing to their advantage in designing a three-dimensional (3D) solid tumor model. For controlling multicellular cancer spheroids, mimicking the tumor extracellular matrix (ECM) microenvironment is important to understand cell-cell and cell-matrix interactions. In drug cytotoxicity assessments, MCTs provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates' effects. To generate incubate multicellular spheroids, researchers have developed several 3D multicellular spheroid culture technologies to establish a research background and a platform using tumor modelingvia advanced materials science, and biosensing techniques for drug-screening. In application, drug screening was performed in both invasive and non-invasive manners, according to their impact on the spheroids. Here, we review the trend of 3D spheroid culture technology and culture platforms, and their combination with various biosensing techniques for drug screening in the biomedical field.
Asunto(s)
Antineoplásicos/farmacología , Evaluación Preclínica de Medicamentos , Neoplasias , Esferoides Celulares , Línea Celular Tumoral , Humanos , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
Eight compounds (1-8) including one novel nitrophenyl glycoside, ginkgonitroside (1) were isolated from the leaves of Ginkgo biloba, a popular medicinal plant. The structure of the new compound was characterized using extensive spectroscopic analyses via 1D and 2D NMR data interpretations, HR-ESIMS, and chemical transformation. To the best of our knowledge, the present study is the first to report the presence of nitrophenyl glycosides, which are relatively unique phytochemicals in natural products, in G. biloba. The isolated compounds (1-8) were examined for their effects on the regulation of mesenchymal stem cell (MSC) differentiation. Compounds 1-3 and 8 were able to suppress MSC differentiation toward adipocytes. In contrast, compounds 5 and 8 showed activity promoting osteogenic differentiation of MSCs. These findings demonstrate that the active compounds showed regulatory activity on MSC differentiation between adipocytes and osteocytes.
Asunto(s)
Adipocitos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ginkgo biloba/química , Glicósidos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Adipocitos/fisiología , Animales , Diferenciación Celular/fisiología , Línea Celular , Glicósidos/química , Ratones , Osteoblastos/fisiología , Hojas de la Planta/químicaRESUMEN
Ginkgo biloba (Ginkgoaceae), commonly known as "ginkgo", is called a living fossil, and it has been cultivated early in human history for various uses in traditional medicine and as a source of food. As part of ongoing research to explore the chemical diversity and biologically active compounds from natural resources, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2) were isolated from the leaves of G. biloba. The coumaric acid-aliphatic alcohol hybrids of natural products have rarely been reported. The structures of the new compounds were determined by extensive NMR spectroscopic analysis, HRESI-MS, and quantum chemical ECD calculations, and by comparing the experimental HRESI-MS/MS spectrum of chemically transformed compound 1a with the predicted HRESI-MS/MS spectra proposed from CFM-ID 3.0, a software tool for MS/MS spectral prediction and MS-based compound identification. Ginkwanghols A (1) and B (2) increased alkaline phosphatase (ALP) production in C3H10T1/2, a mouse mesenchymal stem cell line, in a dose-dependent manner. In addition, ginkwanghols A and B mediated the promotion of osteogenic differentiation as indicated by the induction of the mRNA expression of the osteogenic markers ALP and osteopontin (OPN).
Asunto(s)
Alcoholes/farmacología , Ácidos Cumáricos/farmacología , Ginkgo biloba/química , Hojas de la Planta/química , Alcoholes/química , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Ácidos Cumáricos/química , Ratones , Estructura Molecular , Osteogénesis/efectos de los fármacosRESUMEN
Macrophages play a major role in innate immune responses by producing a variety of immune mediators and cytokines. The stimulation of macrophages by natural products may lead to an enhanced innate immune system. This study evaluated the immunostimulatory effects of a polysaccharide-rich crude fraction of Celosia cristata L. flowers (CCP) on murine macrophages. CCP treatment induced the production of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines by macrophages. Mechanistically, the activation of mitogen-activated protein kinases, NF-κB and toll-like receptor 4 were found to be associated with the stimulatory functions of CCP. CCP was found to be primarily composed of galacturonic acid and glucose in addition to small amounts of arabinose and galactose. This study demonstrated that CCP may enhance the innate immune responses and potentially improve the immune functions in the body.
Asunto(s)
Celosia/química , Flores/química , Factores Inmunológicos/farmacología , Macrófagos/efectos de los fármacos , Polisacáridos/farmacología , Animales , Células Cultivadas , Citocinas/análisis , Citocinas/inmunología , Femenino , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Macrófagos/inmunología , Ratones , Ratones Endogámicos C3H , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Células RAW 264.7RESUMEN
BACKGROUND: Hyperuricemia (HUA) plays an important role in metabolic syndrome, cardiovascular disease, and kidney disease. HUA without resulting gout is referred to as asymptomatic HUA. The purpose of the present systematic review protocol is to provide methods to assess the effectiveness and safety of acupuncture-based treatment for asymptomatic HUA. METHODS: To identify randomized controlled trials (RCTs) involving acupuncture-based treatment for asymptomatic HUA, a search will be carried out using the following eight electronic databases: MEDLINE, EMBASE, Cochrane Library, Korea Med, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, China National Knowledge Infrastructure, and Japanese Institutional Repositories Online. Manual search and email contact with the author will also be conducted if necessary. Studies will be selected based on predefined criteria and summarized data regarding study participants, interventions, control groups, outcome measures, side effects, and risk of bias. No language restrictions will be imposed. Studies that evaluated any type of acupuncture will be eligible for inclusion, and the primary outcome will be the blood uric acid level. The methodological quality of the included RCTs will be assessed using the Cochrane risk of bias tool. RESULTS: The present study will evaluate the efficacy and safety of acupuncture to treat HUA. CONCLUSION: Our findings will establish the evidence for acupuncture-based treatment of HUA and will be informative for patients with HUA, clinicians, policy makers, and researchers. REGISTRATION NUMBER: reviewregistry1054.
Asunto(s)
Terapia por Acupuntura , Hiperuricemia/terapia , Enfermedades Asintomáticas/terapia , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
Rhubarb is a well-known herb worldwide and includes approximately 60 species of the Rheum genus. One of the representative plants is Rheum palmatum, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of R. palmatum inhibited hepatic stellate cell (HSC) activation by transforming growth factor ß1 (TGF-ß1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-O-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-O-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-O-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-O-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-ß1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-O-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-O-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-O-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.
Asunto(s)
Antraquinonas/farmacología , Glucósidos/farmacología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Sustancias Protectoras/farmacología , Rheum/química , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Antraquinonas/química , Etanol , Glucósidos/química , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Fosforilación , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.
Asunto(s)
Cornus/química , Factor de Transcripción E2F1/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Extractos Vegetales/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/metabolismo , Andrógenos/metabolismo , Animales , Biomarcadores , Ciclo Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Humanos , Masculino , Extractos Vegetales/química , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/etiología , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Ratas , Transducción de Señal/efectos de los fármacos , Testosterona/metabolismo , Testosterona/farmacologíaRESUMEN
Phytochemical analysis of methanol extracts of Ginkgo biloba leaves resulted in the isolation of a novel diarylpentanoid, ginkgobilol (1) and a known diarylpentanoid analog (2). The structure of the new compound was elucidated by analyzing NMR spectroscopic data and HR-ESIMS, and the absolute configuration was determined using gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ analysis and specific rotation value. Diarylpentanoids comprise two aromatic rings linked by a five-carbon bridge; these are relatively unique examples in natural products. To the best of our knowledge, the present study is the first to report the presence of diarylpentanoids in G. biloba. Compound 2 increased alkaline phosphatase (ALP) production in C3H10T1/2, a murine mesenchymal stem cell line, in a dose-dependent manner. The promotion of osteogenic differentiation by the active compound 2 mediated by induction of transcriptional ALP and osteopontin (OPN) gene expression was confirmed using quantitative real time polymerase chain reaction, thus indicating its remarkable bone formation activity.
Asunto(s)
Ginkgo biloba/química , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Osteopontina/metabolismo , Fitoquímicos/química , Fitoquímicos/farmacologíaRESUMEN
The present work describes the feasibility of coffee residue extracts as cryoprotective agents in the storage stability of freeze-dried lactic acid bacteria. Coffee residue extracts were extracted from coffee residue, produced after coffee extraction for coffee powder and instant coffee preparation, using an autoclave. Leuconostoc mesenteroides WiKim32 was selected to evaluate the ability of coffee residue extracts to protect bacteria during freeze-dried storage. The storage stability of freeze-dried Leu. mesenteroides WiKim32 with coffee residue extracts was comparable to those with commercial cryoprotective agents. Coffee residue extracts contributed to storage stability immediately after freeze-drying (61.2%) and subsequent storage (48.7%). Our data indicate that the protective effect of the coffee residue extracts is associated with ions, carbohydrates, and phenolic compounds. Coffee residue extracts are feasible materials, which can reduce the storage and distribution costs compared to commercial agents currently available.
Asunto(s)
Café , Lactobacillales , Liofilización , Esperanza de Vida , PolvosRESUMEN
The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1-4), three flavonoid glycosides (5-7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50: 75.47 ± 2.23 µM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Caspasas/metabolismo , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Lespedeza/química , Mitocondrias/metabolismo , Transducción de Señal , Neoplasias de la Mama/metabolismo , Forma del Núcleo Celular/efectos de los fármacos , Cisplatino/farmacología , Activación Enzimática/efectos de los fármacos , Femenino , Glicósidos/química , Humanos , Células MCF-7 , Metanol/química , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Meyer (Araliaceae), has been used in traditional medicine for preventive and therapeutic purposes in Asian countries. One of the active ginsenoside metabolites, 20(S)-Protopanaxatriol (PPT), has been associated with diverse pharmacological effects, including anti-inflammatory properties. AIM OF THE STUDY: Although the capacity of PPT as an anti-inflammatory agent has been studied, this study aimed to explore the intrinsic mechanism of PPT in regulating inflammasome activation-mediated inflammatory responses in experimental models. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-primed peritoneal macrophages in vitro was used to study the role of PPT on inflammasome activation. LPS-induced septic shock and monosodium urate (MSU)-induced murine peritonitis models were employed for in vivo evaluations. RESULTS: PPT attenuated NLRP3 inflammasome activation and also reduced ASC oligomerization, leading to attenuation of interleukin (IL)-1ß secretion. Further, PPT inhibited IL-1ß secretion in both LPS-induced septic shock and MSU-induced mouse peritonitis models. CONCLUSIONS: This study revealed that ginsenoside metabolite PPT, inhibits inflammation-mediated inflammasome activation and supported the traditional use of ginseng in treating various inflammatory disorders.
Asunto(s)
Antiinflamatorios/uso terapéutico , Inflamasomas/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Panax , Peritonitis/tratamiento farmacológico , Sapogeninas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Ginsenósidos/metabolismo , Interleucina-1beta/inmunología , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Ratones Endogámicos C57BL , Peritonitis/inducido químicamente , Peritonitis/inmunología , Sapogeninas/farmacología , Choque Séptico/inmunología , Ácido ÚricoRESUMEN
BACKGROUND: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent.
Asunto(s)
Cornus/química , Factor de Transcripción E2F1/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/metabolismo , Psoralea/química , Animales , Ciclo Celular , Línea Celular , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum (C. indicum), a perennial plant, has long been used to treat inflammation-related disorders, such as pneumonia, hypertension, gastritis, and gastroenteritis. AIM OF THE STUDY: The inhibitory effect of C. indicum extract (C.I) on inflammasome activation was investigated to validate its potential in treating inflammation related disorders. MATERIALS AND METHODS: LPS-primed bone marrow-derived macrophages (BMDMs) were used to confirm the inhibitory effect of C.I on selective inflammasome activation in vitro. A monosodium urate (MSU)-induced murine peritonitis model was employed to study the effect of C.I in vivo. RESULTS: C.I inhibited activation of NLRP3 and AIM2 inflammasomes, leading to suppression of interleukin-1ß secretion in vitro. Further, C.I regulates the phosphorylation of apoptosis-associated speck-like protein containing a CARD (ASC), which could be the main contribution to attenuate these inflammasomes activation. C.I also suppressed secretion of pro-inflammatory cytokines and neutrophils recruitment in MSU-induced murine peritonitis model. CONCLUSIONS: This study provides scientific evidence substantiating the traditional use of C. indicum in the treatment of inflammatory diseases, including gout, which is induced by physiologically analogous cause to MSU-induced peritonitis.
Asunto(s)
Antiinflamatorios/farmacología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Chrysanthemum , Proteínas de Unión al ADN/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Peritonitis/metabolismo , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/uso terapéutico , Femenino , Gota/tratamiento farmacológico , Gota/metabolismo , Supresores de la Gota/farmacología , Supresores de la Gota/uso terapéutico , MAP Quinasa Quinasa 4/metabolismo , Ratones Endogámicos C57BL , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Componentes Aéreos de las Plantas , Extractos Vegetales/uso terapéutico , Ácido ÚricoRESUMEN
Benign prostatic hyperplasia (BPH), an age-dependent disorder with a prevalence percentage of 60% in the 60s, has been found to involve an androgenic hormone imbalance that causes confusion between cell apoptosis and proliferation. Because general medications for BPH treatment have undesirable side effects, the development of effective alternative medicines has been considered. HBX-5 is a newly developed formula with the aim of improving BPH, and is composed of nine medicinal herbs. BPH was induced in the rats by intramuscular injection of testosterone propionate after castration. Rats were divided into six groups, and the efficacy of HBX-5 on testosterone-induced BPH in rats was estimated. In addition, RWPE-1 and WPMY-1 cells were used to demonstrate the effect of HBX-5 on BPH in vitro model. Compared with the control group, HBX-5 administration group suppressed BPH manifestations, such as excessive development of prostate, and increase of serum dihydrotestosterone and 5α-reductase concentrations. Furthermore, immunohistochemistry analysis revealed that HBX-5 significantly decreased the expression of androgen receptor (AR) and proliferating cell nuclear antigen (PCNA). In addition, results of RWPE-1 and WPMY-1 cells showed that HBX-5 inhibited the over-expression of AR and PSA in DHT-induced prostate hyperplastic microenvironments.
Asunto(s)
Extractos Vegetales/administración & dosificación , Plantas Medicinales/química , Hiperplasia Prostática/tratamiento farmacológico , Propionato de Testosterona/efectos adversos , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/sangre , Animales , Línea Celular , Dihidrotestosterona/sangre , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inyecciones Intramusculares , Masculino , Extractos Vegetales/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Hiperplasia Prostática/sangre , Hiperplasia Prostática/inducido químicamente , Ratas , Receptores Androgénicos/metabolismoRESUMEN
Ginseng (the root of Panax ginseng Meyer) fermented by Lactobacillus plantarum has been found to attenuate allergic responses in in vitro and in vivo experimental models. Ginseng has been reported to also possess various biological functions including anti-inflammatory activity. The present study was aimed at comparing the anti-allergic effect of ginseng and fermented ginseng extracts on IgE-mediated passive cutaneous anaphylaxis in vitro in a murine cell line and in vivo in mice. Fermented ginseng extract (FPG) showed higher inhibitory effect against in vitro and in vivo allergic responses when compared with ginseng extract (PG). The secretion of ß-hexosaminidase and interleukin (IL)-4 from the IgE-DNP-stimulated RBH-2H3 mast cells were significantly (p < 0.05) inhibited by FPG treatment, and this effect was concentration-dependent. Further, MKK4 activation and subsequent JNK phosphorylation were attenuated by FPG treatment. The inhibitory effect of FPG on the in vitro allergic response was verified in vivo against IgE-DNP-induced passive cutaneous anaphylaxis in a mouse model. These data indicated that the fermentation of ginseng with L. plantarum enhanced its anti-allergic effects both in vitro and in vivo. We predict that compositional changes in the ginsenosides caused by the fermentation may contribute to the change in the anti-allergic effects of ginseng. The results of our study highlight the potential of the use of FPG as a potential anti-allergic agent.
Asunto(s)
Antialérgicos/farmacología , Fermentación , Panax/química , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antialérgicos/metabolismo , Línea Celular , Supervivencia Celular , Femenino , Ginsenósidos/metabolismo , Ginsenósidos/farmacología , Inmunoglobulina E , Interleucina-4/análisis , Lactobacillus plantarum/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Fosforilación/efectos de los fármacos , Extractos Vegetales/metabolismo , beta-N-Acetilhexosaminidasas/análisisRESUMEN
Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1ß regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1ß levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.
Asunto(s)
Artemisia/química , Proteínas de Unión al ADN/metabolismo , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/uso terapéutico , Animales , Células Cultivadas , Proteínas de Unión al ADN/genética , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1ß secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1ß in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.
RESUMEN
Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.