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1.
J Med Food ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38624298

RESUMEN

Taurine is a nonessential amino acid that has been increasingly consumed due to its various beneficial biological effects. Excessive taurine intake has been linked to the positive regulation of inflammatory responses and endoplasmic reticulum stress through the modulation of intracellular calcium levels. However, research on the potential adverse effects of taurine consumption on the respiratory system is limited. To address this, we investigated the respiratory responses of 6-week-old male Sprague-Dawley rats to taurine administered orally at 0, 100, 200, and 400 mg/kg. Respiratory rate, tidal volume, and minute volume were monitored in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. We found that taurine administration did not significantly alter respiratory rate or tidal volume; however, a significant increase in minute volume was observed 6 h after administration of 200 mg/kg taurine.

2.
J Med Food ; 27(3): 275-278, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38377552

RESUMEN

As caffeine consumption continues to increase, both positive and negative effects are becoming evident. Caffeine directly affects the cardiovascular system, including heart function and rate. Thus, understanding the current respiratory safety pharmacological responses is of utmost importance. To elucidate the respiratory safety pharmacological characteristics of caffeine, male Sprague-Dawley rats, aged 6 weeks, were intravenously administered doses of 0, 2, 6, and 20 mg/kg of caffeine. Respiratory rate, tidal volume, and minute volume were subsequently measured. In this study, we observed a significant increase in respiratory rate and minute volume, but a remarkable reduction in tidal volume following the intravenous administration of caffeine at doses exceeding 6 mg/kg. These changes were evident within the timeframe of 0.25 to 1.5 h. The data we have collected can serve as valuable foundational scientific information for future research on caffeine, encompassing absorption, distribution, metabolism, excretion, and pharmacological core-battery experiments.


Asunto(s)
Pruebas Respiratorias , Cafeína , Ratas , Animales , Masculino , Cafeína/farmacología , Ratas Sprague-Dawley , Volumen de Ventilación Pulmonar , Administración Intravenosa
3.
J Hazard Mater ; 448: 130884, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36736217

RESUMEN

Aluminum oxide nanoparticles (Al2O3 NPs) have recently been reported to cause an inflammatory response in the lungs, and studies are being conducted on their adverse effects, especially in patients with underlying lung diseases such as asthma. However, the underlying mechanism of asthma aggravation caused by Al2O3 NPs remains unclear. This study investigated whether Al2O3 NPs exacerbate ovalbumin (OVA)-induced asthma and focused on the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacerbation. Al2O3 NP exposure in asthmatic mice resulted in increased inflammatory cell counts in the lungs, airway hyperresponsiveness, and increased levels of inflammatory cytokines compared with only OVA-induced mice, and excessive secretion of mucus was observed in the airways. Moreover, Al2O3 NP exposure in OVA-induced mice increased the expression levels of TLR4, phospho-nuclear transcription factor-kappa B (p-NFκB), myeloid differentiation factor 88 (MyD88), and phospho-NF kappa B inhibitor alpha (p-IκBα). Furthermore, in the lungs of TLR4 knockout mice exposed to Al2O3 NPs and in a human airway epithelial cell line with down regulated TLR4, the expression levels of MyD88, p-NFκB, and p-IκBα were decreased, and asthma-related allergic responses were reduced. Therefore, we demonstrated that TLR4 is important for aggravation of asthma induced by Al2O3 NPs, and this study provides useful information regarding as yet undiscovered novel target signaling.


Asunto(s)
Asma , FN-kappa B , Receptor Toll-Like 4 , Animales , Humanos , Ratones , Asma/inducido químicamente , Asma/metabolismo , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Pulmón , Ratones Endogámicos BALB C , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Inhibidor NF-kappaB alfa/farmacología , Ovalbúmina , Fosforilación , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Óxido de Aluminio/efectos adversos , Nanopartículas del Metal/efectos adversos
4.
Biol Trace Elem Res ; 200(7): 3215-3226, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34535882

RESUMEN

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague-Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.


Asunto(s)
Óxido de Aluminio , Nanopartículas , Administración Oral , Óxido de Aluminio/toxicidad , Animales , Peso Corporal , Femenino , Masculino , Nanopartículas del Metal/toxicidad , Nanopartículas/toxicidad , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley
5.
Biomed Pharmacother ; 145: 112410, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34775237

RESUMEN

BACKGROUND: Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. PURPOSE: In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. METHODS: The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. RESULTS: PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. CONCLUSION: Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.


Asunto(s)
Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Phlomis/química , Extractos Vegetales/farmacología , Animales , Antiasmáticos/administración & dosificación , Antiasmáticos/aislamiento & purificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Inflamación/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/genética , Ratones , Ratones Endogámicos BALB C , Farmacología en Red , Ovalbúmina , Fosforilación/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Hipersensibilidad Respiratoria/tratamiento farmacológico , Factor de Transcripción ReIA/metabolismo
6.
Toxicol Res ; 37(3): 385-393, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34295802

RESUMEN

Dioscorea Rhizome is commonly used in traditional herbal medicines for the treatment of diabetes, hyperthyroidism, liver damage, neuropathy, and asthma. Here, we investigated the genotoxicity potential of D. Rhizome water extract (DRWE) using three standard battery systems in accordance with the test guidelines of the Organisation for Economic Cooperation and Development and Ministry of Food and Drug Safety as well as the principles of Good Laboratory Practice. A bacterial reverse mutation test (Ames test) was performed using the direct plate incorporation method in the presence or absence of a metabolic activation system (S9 mixture). The tester strains used included four histidine auxotrophic strains of Salmonella typhimurium, TA100, TA1535, TA98, and TA1537, along with a tryptophan auxotrophic strain of Escherichia coli, WP2 uvrA. An in vitro chromosome aberration test was performed using CHL/IU cells originally derived from the lung of a female Chinese hamster in the presence or absence of the S9 mixture. An in vivo mouse bone marrow micronucleus test was performed using male ICR mice. The micronucleus was confirmed after observation of the micro-nucleated polychromatic. The Ames test showed that DRWE did not induce gene mutations at any dose level in any of the tested strains. Additionally, DRWE did not result in any chromosomal aberrations specified in the in vitro chromosomal aberration and in vivo micronucleus tests. These results showed that DRWE exhibited neither mutagenic nor clastogenic potential in either the in vitro or in vivo test systems.

7.
Regul Toxicol Pharmacol ; 125: 105001, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34242707

RESUMEN

This study was conducted to investigate the potential toxicity of repeated oral dose of SUNACTIVE Zn-P240, a new type of zinc supplement, in Sprague-Dawley rats. SUNACTIVE Zn-P240 was administered once daily by gavage at doses of 0, 500, 1000, and 2000 mg/kg/day for each group over a 28-day period. At 2000 mg/kg/day, there were increases in serum alkaline phosphatase (ALP) and alanine aminotransferase, liver weight, histopathological changes in stomach, liver, and pancreas and decreases in body weight, food consumption, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein (TP), and albumin. At 1000 mg/kg/day, there was an increase in the serum ALP level and there were decreases in the MCV, MCH, and TP. There were no treatment-related adverse effects in the 500 mg/kg/day group. Under the present experimental conditions, the target organs in rats were determined to be the stomach, pancreas, liver, and erythrocyte and the no-observed-adverse-effect level (NOAEL) in rats was considered to be 500 mg/kg/day.


Asunto(s)
Suplementos Dietéticos/toxicidad , Zinc/farmacología , Animales , Relación Dosis-Respuesta a Droga , Eritrocitos/efectos de los fármacos , Femenino , Hígado/efectos de los fármacos , Masculino , Nanotecnología , Nivel sin Efectos Adversos Observados , Páncreas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estómago/efectos de los fármacos
8.
Artículo en Inglés | MEDLINE | ID: mdl-34055011

RESUMEN

Yijin-tang is an oriental traditional herb used to treat inflammatory diseases. In the present study, we investigated the protective effects of Yijin-tang water extract (YTE) using an ovalbumin- (OVA-) induced asthma model, focusing on the antioxidant and anti-inflammatory properties of the herb. BALB/c mice were intraperitoneally injected with OVA on days 0 and 14 and then challenged with OVA on days 21, 22, and 23. The animals were orally administered YTE (200 and 400 mg/kg) from days 18 to 23, and this was found to significantly decrease airway hyperresponsiveness and release of inflammatory cells, cytokines, and OVA-specific immunoglobulin E in mice with asthma. In addition, YTE was associated with a marked reduction in airway inflammation and mucus production in lung tissue of mice with asthma. Furthermore, YTE suppressed the expression of matrix metalloproteinase-9 and phosphorylation of ERK in the lungs, which in turn led to a reduction in inducible nitric oxide synthases and an elevation in reduced glutathione and heme oxygenase-1. In conclusion, YTE effectively suppressed allergic responses in mice with asthma and the effect was closely related to antioxidant and anti-inflammatory properties of the herb. Our results indicate that YTE may be a potential agent for the treatment of allergic asthma.

9.
Regul Toxicol Pharmacol ; 120: 104844, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33359266

RESUMEN

Dioscorea Rhizome is widely used as a traditional herbal medicine to treat asthma, diarrhea, cough, bronchitis, spermatorrhea, leukorrhea, and rheumatoid arthritis. This study investigated the potential subchronic toxicity of a D. Rhizome water extract (DRWE) after repeated oral administration at 0, 800, 2000, and 5000 mg/kg/day in rats for 13 weeks. During the study period, clinical signs, mortality, body weight, food consumption, water consumption, urinalysis, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. The 13-week repeated oral administration of DRWE to rats resulted in an increased incidence of zona glomerulosa hypertrophy and hyperplasia in the adrenal gland at dose levels of ≥2000 mg/kg/day in both sexes. However, these findings are considered as non-adverse adaptive changes because of minimal histological changes in the lesions, which were not accompanied by any corresponding alterations in serum electrolytes and adrenal gland weight. No treatment-related adverse effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of the DRWE was considered to be 5000 mg/kg/day in both sexes, and no target organs were identified.


Asunto(s)
Dioscorea/toxicidad , Extractos Vegetales/toxicidad , Rizoma/toxicidad , Pruebas de Toxicidad Subcrónica/métodos , Agua , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/fisiología , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
10.
J Ethnopharmacol ; 267: 113621, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33246125

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodi radix is widely used in traditional herbal medicine for bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. However, data on safety of Platycodi radix are insufficient. AIM OF THE STUDY: The present study was performed to evaluate the potential subchronic toxicity of Platycodi radix water extract through a 13-week repeated oral dose experiment in Sprague-Dawley rats. MATERIALS AND METHODS: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 300, 1000, and 3000 mg/kg/day of Platycodi radix water extract and a vehicle control group receiving sterile distilled water for 13 weeks. RESULTS: Repeated oral administration of the Platycodi radix water extract to rats resulted in an increased incidence of centrilobular hepatocellular hypertrophy in the liver, diffuse follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia of the limiting ridge in the stomach at dose levels of ≥500 mg/kg/day of both genders. However, these findings are considered be adaptive non-adverse changes because these findings were observed without organ weight change or clinical pathology alterations. No treatment-related effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested. CONCLUSION: Under the present experimental conditions, the no-observed-adverse-effect level of the Platycodi radix water extract was considered to be ≥ 3000 mg/kg/day in rats, and no target organs were identified.


Asunto(s)
Extractos Vegetales/toxicidad , Raíces de Plantas/toxicidad , Platycodon/toxicidad , Pruebas de Toxicidad Subcrónica , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Platycodon/química , Ratas Sprague-Dawley , Medición de Riesgo , Factores de Tiempo
11.
J Ethnopharmacol ; 260: 112988, 2020 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-32446926

RESUMEN

ETHNOPHAMACOLOGICAL RELEVANCE: Sam So Eum (SSE), used in traditional Korean medicine, has been prescribed for the treatment of various ailments including emesis, and fever for centuries. SSE is known by several different names (Shen Su Yin in traditional Chinese medicine; Jin So In traditional Japanese Kampo medicine). It is a mixture of medicinal plants including Panax ginseng C. A. Mey., Perilla frutescens (L.) Britton, and Peucedanum praeruptorum Dunn. Studies have revealed that SSE has many pharmacological effects including anti-inflammatory, anti-cancer, and anti-allergic properties, but its toxic effects have not been evaluated in vivo. Recently, the use of traditional medicinal herbs to treat various diseases has increased, owing to increased number of studies supporting their efficacy. However, safety evaluations for toxicity and other adverse effects have not been extensive. It is commonly considered that natural products extracted from traditional medicinal herbs are safer than synthetic drugs, but this lacks a scientific basis. Thus, in this study, we evaluated the toxicity of SSE in male and female rats. AIM OF THE STUDY: To evaluated the safety of SSE in male and female rats. MATERIALS AND METHODS: SSE was administered orally for 13 weeks at 1000, 2000, and 4000 mg kg-1·day-1, and then the rats were maintained for 4 weeks without SSE administration (recovery evaluation). RESULTS: We observed the animals for changes in clinical signs, including hematological parameters, and food consumption; serum chemistry profiling and urinalysis were also carried out. Creatinine levels in the serum were significantly increased following oral administration of SSE at 2000 and 4000 mg kg-1·day-1 in male and female rats, but returned to the normal levels during the recovery period. In addition, SSE administration does not cause kidney and liver toxicity. Thus, we determined that the no-observed-adverse-effect level of SSE is 4000 mg kg-1·day-1. The no-observed-effect level of SSE was determined to be 1000 mg kg-1·day-1, because serum creatinine was increased by oral administration of SSE at 2000 and 4000 mg kg-1·day-1 in male and female rats. CONCLUSIONS: SSE administration does not cause toxicity at 4000 mg kg-1·day-1 in male and female rats.


Asunto(s)
Creatinina/sangre , Extractos Vegetales/toxicidad , Pruebas de Toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley
12.
Cells ; 9(3)2020 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-32164364

RESUMEN

Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Dióxido de Silicio/uso terapéutico , Silibina/uso terapéutico , Animales , Antineoplásicos Fitogénicos/farmacología , Humanos , Inflamación , Ratones , Nanopartículas , Transducción de Señal , Dióxido de Silicio/farmacología , Silibina/farmacología
13.
Antioxidants (Basel) ; 9(2)2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-31991647

RESUMEN

Scrophularia koraiensis Nakai (Scrophulariaceae) is a medicinal herb that grows in Korea and which has been widely used to treat fever, edema, neuritis and laryngitis. Hence, we evaluated the anti-inflammatory and antioxidant effects of the ethanol extract (SKE) of S. koraiensis Nakai in an ovalbumin (OVA)-induced mouse model. We injected 20 µg of OVA with 2 mg of aluminum on day 0 and day 14 to induce allergic airway inflammation in six-week-old BALB/c mice, and mice were challenged with 1% OVA by nebulization for 1 h on days 21, 22, and 23. SKE was orally administered at 20 mg/kg and 40 mg/kg from day 18 to 23, and its effects were compared with those of montelukast treatment. SKE significantly reduced proinflammatory cytokines, inflammatory cell counts, immunoglobulin-E, and airway hyperresponsiveness during the OVA-induced allergic airway inflammation model; it also reduced airway inflammation and mucus production. In addition, SKE reduced the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation in lung tissues while enhancing nuclear factor erythroid-derived 2-related factor (Nrf-2) and heme oxygenase-1 (HO-1) expression. In conclusion, SKE showed the protective effects on OVA-induced allergic airway inflammation via the suppression of NF-κB phosphorylation and the enhancement of the Nrf2/HO-1 signaling pathway. These results indicate that SKE is a potential therapeutic agent for allergic airway inflammation.

14.
Phytomedicine ; 67: 153159, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31901567

RESUMEN

BACKGROUND: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis. PURPOSE: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. METHODS: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation. RESULTS: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells. CONCLUSION: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma.


Asunto(s)
Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Scrophularia/química , Animales , Asma/inducido químicamente , Modelos Animales de Enfermedad , Femenino , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/fisiopatología , Inmunoglobulina E/metabolismo , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversos , Fosforilación/efectos de los fármacos , Células RAW 264.7
15.
Phytother Res ; 34(3): 624-633, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31724257

RESUMEN

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.


Asunto(s)
Antiinflamatorios/farmacología , Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Propionatos/farmacología , Animales , Asma/inducido químicamente , Asma/patología , Líquido del Lavado Bronquioalveolar , Ácidos Cumáricos , Ciclooxigenasa 2/análisis , Citocinas/análisis , Femenino , Inmunoglobulina E/sangre , Inflamación/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Metaloproteinasa 9 de la Matriz/análisis , Ratones , Ratones Endogámicos BALB C , Moco/metabolismo , Óxido Nítrico Sintasa de Tipo II/análisis , Ovalbúmina/efectos adversos , Organismos Libres de Patógenos Específicos
16.
Regul Toxicol Pharmacol ; 109: 104487, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31585136

RESUMEN

Cassia tora Linn. is an annual or perennial plant of the Fabaceae/Leguminosae family. It is used in traditional medicine for various biological activities including anti-constipation, anti-inflammatory, visual acuity, and hepato-protective activities. The present study was carried out to investigate the potential toxicity of C. tora L. seed ethanol extract (CTSEE) following a 13-week repeated oral administration to Sprague-Dawley rats. CTSEE was administered orally to male and female rats for 13 weeks at 0 (control), 500, 1000, and 2000 mg/kg/day (n = 10, for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 4-week recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples collected. There were no treatment-related adverse effects in clinical signs, body weight, food consumption, estrous cycle, sperm parameters, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any doses tested. Under the present experimental conditions, the no-observed-adverse-effect level of the CTSEE was >2000 mg/kg/day in both genders, and no target organs were identified.


Asunto(s)
Cassia/química , Extractos Vegetales/toxicidad , Administración Oral , Animales , Etanol/química , Femenino , Masculino , Medicina Tradicional/métodos , Nivel sin Efectos Adversos Observados , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Semillas/química , Pruebas de Toxicidad Subcrónica
17.
Toxicol Res ; 35(2): 191-200, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31015901

RESUMEN

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

18.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30991656

RESUMEN

Dipsacus asperoides C. Y. Cheng et T. M. Ai (DA) has been used in China as a traditional medicine to treat lumbar and knee pain, liver dysfunction, and fractures. We explored the suppressive effect of DA on allergic asthma using an ovalbumin (OVA)-induced asthma model. In the asthma model, female Balb/c mice were sensitized to OVA on day 0 and 14 to boost immune responses and then exposed to OVA solution by using an ultrasonic nebulizer on days 21 to 23. DA (20 and 40 mg/kg) was administered to mice by oral gavage on days 18 to 23. Methacholine responsiveness was determined on day 24 using a plethysmography. On day 25, we collected bronchoalveolar lavage fluid, serum, and lung tissue from animals under anesthesia. DA treatment effectively inhibited methacholine responsiveness, inflammatory cell infiltration, proinflammatory cytokines such as interleukin (IL)-5 and IL-13, and immunoglobulin (Ig) E in OVA-induced asthma model. Reductions in airway inflammation and mucus hypersecretion, accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of nuclear factor kappa B (NF-κB), were also observed. Our results indicated that DA attenuated the asthmatic response, and that this attenuation was closely linked to NF-κB suppression. Thus, this study suggests that DA is a potential therapeutic for allergic asthma.


Asunto(s)
Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Dipsacaceae , Medicamentos Herbarios Chinos/uso terapéutico , Animales , Antiinflamatorios/química , Asma/etiología , Asma/inmunología , Dipsacaceae/química , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Femenino , Inmunoglobulina E/inmunología , Interleucina-13/inmunología , Interleucina-5/inmunología , Ratones Endogámicos BALB C , FN-kappa B/inmunología , Ovalbúmina/inmunología
19.
Phytomedicine ; 59: 152777, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31004880

RESUMEN

BACKGROUND: Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation. PURPOSE: We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells. METHODS: CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting. RESULTS: MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells. CONCLUSION: Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.


Asunto(s)
Fumar Cigarrillos/efectos adversos , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Pulmón/efectos de los fármacos , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/genética , Medicamentos Herbarios Chinos/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Lipopolisacáridos/toxicidad , Pulmón/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Fosforilación/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/patología
20.
Int Immunopharmacol ; 68: 124-130, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30622029

RESUMEN

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.


Asunto(s)
Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Cisteína/análogos & derivados , Eosinofilia/tratamiento farmacológico , Alérgenos , Animales , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/inmunología , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Cisteína/farmacología , Cisteína/uso terapéutico , Citocinas/inmunología , Modelos Animales de Enfermedad , Eosinofilia/inmunología , Eosinofilia/patología , Femenino , Inmunoglobulina E/sangre , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos BALB C , Moco/metabolismo , Ovalbúmina
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