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1.
J Vet Sci ; 21(3): e39, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476313

RESUMO

BACKGROUND: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. OBJECTIVES: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. METHODS: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. RESULTS: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. CONCLUSIONS: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

2.
Nutrients ; 12(5)2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32349329

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and cutaneous dry skin. Here, we investigated whether topical application of NI-01 composed of six herbal medicines has a therapeutic effect on AD in vivo. Twelve marker compounds of NI-01 were analyzed by high-performance liquid chromatography with a photodiode array detector for quality control. To induce AD, house dust mite extract was applied to the shaved dorsal skin and ear surfaces of NC/Nga mice twice a week for 6 weeks. NI-01 (1, 2, or 4 mg/mouse) was applied daily to the site for experiment periods. The coefficient of determination of each compound showed good linearity (≥ 0.9999). The recovery rate of the 12 marker components was 96.77%-105.17%; intra and interday precision and repeatability were ≤ 1.40%. Topical application of NI-01 reduced house dust mite induced AD symptoms. The increased expressions of interleukin-4 and intercellular adhesion molecule-1 caused by house dust mites were markedly suppressed in NI-01-treated mice. Corticosterone levels significantly decreased, whereas serotonin levels increased with NI-01 application. These results suggest that NI-01 alleviates AD symptoms by inhibiting infiltration of inflammatory cells, thereby decreasing AD-related stress. NI-01 could be beneficial for the treatment of AD-like skin diseases.

3.
J Ethnopharmacol ; 252: 112551, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31923540

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bojungikki-tang is a traditional herbal medicine used to boost immunity and reduce fatigue. However, there is not enough scientific evidence about its toxicological safety profile to support its continued clinical application. AIM OF THE STUDY: The objective of this study was to investigate the subchronic toxicity profile of Bojungikki-tang water extract (BITW) in Sprague Dawley rats who were exposed to it in multiple doses and various concentrations. MATERIALS AND METHODS: BITW was administered to rats orally, once daily at doses of 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. We checked toxicological parameters including general observations, organ/body weights, food consumption, ophthalmological signs, hematological and serum biochemical values, urinalysis values and histopathological findings. RESULTS: The 13 week repeated oral administration of BITW to rats at doses at doses levels of less than or equal to 2000 mg/kg/day caused no significant toxicological changes and only minor nonsignificant changes. CONCLUSIONS: Our findings indicate that administration of BITW for up to 13 weeks may be safe and nontoxic, with a no-observed-adverse-effect-level of >2000 mg/kg/day for both male and female rats.

4.
J Clin Med ; 8(10)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569833

RESUMO

Conventional and herbal drugs are frequently used together to treat many disorders. Samryungbaekchul-san (SRS, a herbal formula) and otilonium bromide (OB, an antispasmodic agent) are widely used to treat diarrhea-predominant irritable bowel syndrome (D-IBS) in Eastern Asian countries. However, there have been no studies on the co-administration of SRS and OB. Therefore, we aimed to preliminarily assess the feasibility of SRS combined with OB for D-IBS treatment in a pilot double-blind, four-arm, parallel-group, randomized controlled trial (RCT), including 80 patients diagnosed with D-IBS according to the Rome III criteria. The patients were randomly assigned to four treatment groups and were administered drugs for eight weeks after a two-week preparatory period. Follow-up was conducted four weeks after the administration period. The primary outcome was evaluated by using a global D-IBS symptom improvement score; no statistically significant difference was observed between the groups. However, multiple logistic regression analysis of primary outcome scores shows that SRS significantly improved D-IBS symptoms (p < 0.05). For secondary outcomes, better results were observed in the SRS + OB group, in terms of symptoms, including abdominal pain, discomfort, frequency of abdominal pain, and stool form than in OB alone or placebo groups (p < 0.05). In conclusion, the co-administration of SRS and OB might be an effective and safe strategy for the treatment of D-IBS. Large-scale RCTs are warranted to further confirm and clarify these findings.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31223325

RESUMO

Ssanghwa-tang (SHT), a traditional herbal formula, has been widely used to recover fatigue or consumptive disease after an illness. Along with much attention to herbal formula, the concerns about the safety and toxicity have arisen. To establish the safety information, SHT was administrated in Crl:CD Sprague Dawley rats at a daily dose of 0, 1000, 2000, and 5000 mg/kg for 4 weeks. During the test periods, we examined the mortality, clinical observation, body weight change, food consumption, organ weights, hematology, serum biochemistry, and urinalysis parameters. No changes of mortality and necropsy findings occurred in any of the groups during the experimental period. In either sex of rats treated with SHT at 5000 mg/kg/day, changes were observed in food intake, reticulocyte, total bilirubin, some urinalysis parameters, and relative organ weights. The results indicated that SHT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. This dosage was considered no observed adverse effect level (NOAEL) and was appropriate for a 13-week subchronic toxicity study.

6.
J Ethnopharmacol ; 240: 111913, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31091465

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gyejibokryeong-hwan is a traditional herbal medicine and is reported to have various pharmacological actions. Despite many reports of previous studies, there is limited scientific evidence concerning its safety and few drug-metabolism profiles to support the continued therapeutic application of Gyejibokryeong-hwan. AIM OF THE STUDY: The purpose of the present study was to investigate the acute and subacute toxicity profile of a Gyejibokryeong-hwan water extract (GBHW) in vivo, and its effects on the activities of drug-metabolizing enzymes in vitro. MATERIALS AND METHODS: Acute and subacute toxicity was evaluated by giving GBHW to rats. In a study of acute toxicity, the rats were given GBHW by single oral gavage administration at 0 and 5000 mg/kg. In a study of subacute toxicity, rats were given GBHW by oral gavage at 0, 1000, 2000, and 5000 mg/kg/day daily for 28 days. The activities of the major human microsomal cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) isozymes were investigated using fluorescence- and luminescence-based enzyme assays in vitro, respectively. RESULTS: GBHW did not cause any mortality in the study of acute toxicity. In the study of subacute toxicity, GBHW at more than 2000 mg/kg/day was observed with minor changes in the absolute and relative organ weight, hematology, serum biochemistry and urinalysis parameters in rats of either sex. However, these changes were not considered to be important toxicologically. GBHW moderately inhibited the activities of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4, and UGT1A1. CONCLUSIONS: Our present data suggest that GBHW does not cause toxicologically important adverse events at doses up to 2000 mg/kg/day in the 4-week repeated dose toxicity study and provide valuable information concerning its potential to interact with conventional medicine.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Extratos Vegetais/toxicidade , Animais , Feminino , Masculino , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Água/química
7.
J Ethnopharmacol ; 238: 111852, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30954616

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment of inflammatory and viral diseases. However, the safety of Yongdamsagan-tang has not been established. AIM OF THE STUDY: To evaluate the subacute toxicity of Yongdamsagan-tang water extract (YSTE) in Crl:CD Sprague Dawley rats. MATERIALS AND METHODS: We evaluated the subacute toxicity of YSTE in male and female Crl:CD Sprague Dawley rats (n = 5 per group). Rats were treated with YSTE at doses of 0, 1000, 2000 and 5000 mg/kg administered once a day by oral gavage for 4 weeks. RESULTS: There were no significant changes in mortality, body weight, food intake, serum biochemistry, or results of hematology and urinalysis after YSTE administration. However, all rats treated with 5000 mg/kg/day YSTE exhibited excessive salivation and discolored urine. Necropsy findings showed discoloration in the liver of both male (n = 1) and female (n = 3) rats treated with 5000 mg/kg/day YSTE, and an increase in the relative weights of kidney and liver was also found in male rats treated with 5000 mg/kg/day. In addition, decreases in serum creatinine, total bilirubin, alanine transaminase, and alkaline phosphatase were observed in male rats treated with 2000 or 5000 mg/kg/day YSTE. CONCLUSIONS: Abnormalities in some rats are considered to be independent of YSTE toxicity. Therefore, the results suggest that oral administration of YSTE in rats for 4 weeks is safe at doses of up to 5000 mg/kg/day.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Administração Oral , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Bilirrubina/sangue , Creatinina/sangue , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Testes de Toxicidade Subaguda
8.
Molecules ; 24(2)2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30642008

RESUMO

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C4 (LTC4) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC4 by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Antialérgicos/química , Anti-Inflamatórios/química , Biomarcadores , Linhagem Celular , Quimiocinas/metabolismo , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Humanos , Estrutura Molecular , NF-kappa B/metabolismo , Fosforilação , Fator de Transcrição STAT1/metabolismo
9.
Saudi Pharm J ; 27(1): 145-153, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30662318

RESUMO

Samryeongbaekchul-san (SBS) is a traditional herbal formula, which is used for the treatment of dyspepsia, chronic gastritis, and anorexia in Korea. To evaluate the quality of SBS decoction by quantifying its main constituents simultaneously using high-performance liquid chromatography coupled with photodiode array (HPLC-PDA) detection, and secondly to determine the antiadipogenic effect of SBS decoction. The main constituents in a 10-µL injection volume of the decoction were separated on Gemini C18 and Luna NH2 columns (both 250 mm × 4.6 mm, 5 µm) at 40 °C using a gradient of two mobile phases eluting at 1.0 mL/min. 3T3-L1 preadipocytes were differentiated into adipocytes for 8 days with or without SBS. After differentiation, accumulated triglyceride contents and leptin production were measured. The correlation coefficients of all constituents in a calibration curve were ≥0.9998 and showed good linearity in the tested concentration range after validation of the method established. The recovery of the four major compounds were 99.46-102.61% with intra- and interday precisions of 0.08-1.01% and 0.15-0.99%, respectively. The four compounds in the lyophilized SBS sample were detected up to 6.46 mg/g. SBS treatment of the differentiated adipocytes significantly inhibited lipid accumulation and leptin production without cytotoxicity. Optimized simultaneous determination of constituents by HPLC-PDA detection will help to improve quality assessment of SBS or related formulas. SBS has an antiadipogenic effect and further investigation to establish the mechanisms of action of its antiadipogenic effect is warranted.

10.
J Med Food ; 21(11): 1173-1187, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30457473

RESUMO

In the present study, Bojungikgi-tang (BJIKT: Buzhongyiqi-tang, Hochuekki-to) and Palmijihwang-hwan (PMJHH: Baweidìhuang-wan, Hachimijio-gan), traditional herbal formulas, investigated anti-inflammatory efficacies in murine macrophage cell line and the influence on the activities of drug-metabolizing enzymes (DMEs). The anti-inflammatory potentials of the herbal formulas were evaluated to inhibit the production of the inflammatory mediators and cytokines and the protein expression of inducible nitric oxide and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The activities of the major human DMEs, cytochrome P450 isozymes (CYP450s) and UDP-glucuronosyltransferase isozymes (UGTs), were measured by in vitro enzyme assay systems. BJIKT and PMJHH significantly suppressed the prostaglandin E2 (PGE2) production (IC50 = 317.3 and 282.2 µg/mL, respectively) and the protein expression of COX-2 in LPS-treated RAW264.7 cells. On the human microsomal DMEs, BJIKT inhibited the activities of CYP1A2 (IC50 = 535.05 µg/mL), CYP2B6 (IC50 > 1000 µg/mL), CYP2C9 (IC50 = 800.78 µg/mL), CYP2C19 (IC50 = 563.11 µg/mL), CYP2D6 (IC50 > 1000 µg/mL), CYP2E1 (IC50 > 1000 µg/mL), CYP3A4 (IC50 = 879.60 µg/mL), UGT1A1 (IC50 > 1000 µg/mL), and UGT1A4 (IC50 > 1000 µg/mL), but it showed no inhibition of the UGT2B7 activity at doses less than 1000 µg/mL. PMJHH inhibited the CYP2D6 activity (IC50 = 280.89 µg/mL), but IC50 values of PMJHH exceeded 1000 µg/mL on the activities of CYP1A2, CYP2C19, CYP2E1, and CYP3A4. At concentrations less than 1000 µg/mL, PMJHH did not affect the activities of CYP2B6, CYP2C9, UGT1A1, UGT1A4, and UGT2B7. The results indicate that both BJIKT and PMJHH may be potential candidates to prevent and treat PGE2- and COX-2-mediated inflammatory diseases. In addition, this study will expand current knowledge about herb-drug interactions by BJIKT and PMJHH.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores Enzimáticos/farmacologia , Macrófagos/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Composição de Medicamentos , Inibidores Enzimáticos/química , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/metabolismo , Humanos , Macrófagos/enzimologia , Macrófagos/imunologia , Camundongos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/imunologia , Extratos Vegetais/química , Células RAW 264.7
11.
Artigo em Inglês | MEDLINE | ID: mdl-30228826

RESUMO

We had tested antiobesity effect of 52 traditional herbal formulas in 3T3-L1 adipocyte, and Banhasasim-tang (BHSST) was chosen as one of the effective medications to inhibit triglyceride accumulation. We investigated the antiobesity effect of BHSST on 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese mice. In addition, we evaluated the acute toxicity of BHSST in Sprague Dawley (SD) rats. Differentiated 3T3-L1 cells were treated with various concentrations of BHSST for 8 days. Accumulated triglyceride level and the expressions of adipogenesis-related genes and proteins were subsequently investigated. To evaluate the single oral toxicity of BHSST, the SD rats of each sex were administered a single dose (5000 mg/kg) of BHSST via oral gavage; the control group received vehicle only. After a single administration, the mortality, clinical signs, gross findings, and body weight were monitored for 15 days. Male C57BL/6J mice were fed HFD for 4 weeks to induce obesity and randomly received 50 mg/kg of Orlistat (n=12, OR), 200 mg/kg of BHSST (n=12, B200), and 1000 mg/kg of BHSST (n=12, B1000) for another 8 weeks. BHSST suppressed the triglyceride contents and lipid accumulation in a dose-dependent manner in 3T3-L1 adipocytes. BHSST also downregulated the adipogenesis-related gene levels and protein expression compared with those in undifferentiated adipocytes. In a single oral dose toxicity study, there was no adverse effect on mortality, clinical signs, body weight changes, and gross findings in the treatment group. HFD-fed mice treated with BHSST showed significantly reduced body weight gain, food efficiency ratio, and white adipose tissue weight. The medial lethal dose (LD50) of BHSST was 5000 mg/kg/day body weight for each sex in the rats. BHSST decreased the body weight gain in HFD-fed obese mice and inhibited triglyceride accumulation via a cascade of multiple factors at the mRNA and protein levels in 3T3-L1 adipocytes.

12.
Regul Toxicol Pharmacol ; 98: 88-97, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30026136

RESUMO

Oryeong-san is a traditional herbal formula that is used for the treatment of common genitourinary diseases in Korea and other Asian countries. However, little is known about its safety and influence on drug metabolism. In the present study, we investigated the subacute toxicity of an Oryeong-san water extract (OSWE) in rats and its effects on activities of drug-metabolizing enzymes. Subacute toxicity was modeled in animals exposed to treatment with the extract at multiple doses. Rats were given OSWE by oral gavage at 0, 1000, 2000 and 5000 mg/kg/day for 4 weeks. We checked general observations and investigated any changes of body/organ weight, food consumption, hematology, serum biochemistry, and urinalysis in vivo; and the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferase (UGT) isozymes in vitro. We found that OSWE caused no significant toxicological changes at the doses tested. Therefore, the no observed adverse effect level of OSWE was more than 5000 mg/kg/day for male and female rats. OSWE inhibited the activities of CYP2C19 (IC50: 737.69 µg/mL) and CYP2E1 (IC50: 177.77 µg/mL). These results indicate that OSWE may be safe with no drug-related toxicity for up to 4 weeks and provide useful information concerning its potential to interact with conventional drugs or other herbal medicines.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Glucuronosiltransferase/metabolismo , Animais , Feminino , Masculino , Medicina Tradicional Coreana , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , República da Coreia , Medição de Risco , Testes de Toxicidade Subaguda
13.
J Ethnopharmacol ; 224: 441-450, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29920360

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal formula Gyejibokryeong-hwan (GJBRH; Guizhifuling-wan, Keishibukuryo-gan) consisting five medicinal herbs has been used to treat uterine disorders, gynecological diseases and blood stasis syndrome in Asia. AIM OF THE STUDY: We evaluated the safety of GJBRH in Crl:CD Sprague-Dawley (SD) rats over a period of 13 weeks. MATERIALS AND METHODS: To confirm the stability of the components of GJBRH, we analyzed the component contents in GJBRH at different storage periods, using high-performance liquid chromatography. Male and female SD rats were orally administered with GJBRH at doses of 0, 1000, 2000 and 5000 mg/kg/day for 13 weeks and assessed after a 4-week recovery period. Mortality, changes in body weight and food consumption, organ weights, hematology and serum biochemistry were monitored during the experimental period, along with clinical observations, ophthalmological examinations, urinalysis and histopathology. RESULTS: There were no significant differences among the eight marker compounds in GJBRH according to storage period. No significant GJBRH-treatment-related toxicological changes were observed in mortality or ophthalmological examinations in either sex. However, soft feces were observed in the male 5000 mg/kg/day group. In addition, there were significant changes in body weight and food consumption in both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day. In the hematological examinations, we found a significant increase in white blood cells, neutrophils and fibrinogen in the 5000 mg/kg/day groups. In the urinalysis, a decrease in the total protein and albumin and an increase in the ovalbumin/globulin ratio were observed in both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day. Histopathological examinations revealed erosion/ulcers and dilated glands in the stomachs of males from the 5000 mg/kg/day group, and squamous cell hyperplasia and epithelial atrophy was observed in the stomachs of both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day. CONCLUSION: The no-observed-adverse-effect level (NOAEL) was 2000 mg/kg/day for both sexes.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Animais , Atrofia/induzido quimicamente , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Medicamentos de Ervas Chinesas/análise , Ingestão de Alimentos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Hiperplasia/induzido quimicamente , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologia , Estômago/efeitos dos fármacos , Estômago/patologia , Testes de Toxicidade Subcrônica
14.
Am J Physiol Endocrinol Metab ; 315(3): E340-E356, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29533741

RESUMO

Macrophages are phagocytes that play important roles in health and diseases. Acyl-CoA:cholesterol acyltransferase 1 (ACAT1) converts cellular cholesterol to cholesteryl esters and is expressed in many cell types. Unlike global Acat1 knockout (KO), myeloid-specific Acat1 KO ( Acat1-) does not cause overt abnormalities in mice. Here, we performed analyses in age- and sex-matched Acat1-M/-M and wild-type mice on chow or Western diet and discovered that Acat1-M/-M mice exhibit resistance to Western diet-induced obesity. On both chow and Western diets, Acat1-M/-M mice display decreased adipocyte size and increased insulin sensitivity. When fed with Western diet, Acat1-M/-M mice contain fewer infiltrating macrophages in white adipose tissue (WAT), with significantly diminished inflammatory phenotype. Without Acat1, the Ly6Chi monocytes express reduced levels of integrin-ß1, which plays a key role in the interaction between monocytes and the inflamed endothelium. Adoptive transfer experiment showed that the appearance of leukocytes from Acat1-M/-M mice to the inflamed WAT of wild-type mice is significantly diminished. Under Western diet, Acat1-M/-M causes suppression of multiple proinflammatory genes in WAT. Cell culture experiments show that in RAW 264.7 macrophages, inhibiting ACAT1 with a small-molecule ACAT1-specific inhibitor reduces inflammatory responses to lipopolysaccharide. We conclude that under Western diet, blocking ACAT1 in macrophages attenuates inflammation in WAT. Other results show that Acat1-M/-M does not compromise antiviral immune response. Our work reveals that blocking ACAT1 suppresses diet-induced obesity in part by slowing down monocyte infiltration to WAT as well as by reducing the inflammatory responses of adipose tissue macrophages.


Assuntos
Acetil-CoA C-Acetiltransferase/genética , Acetil-CoA C-Acetiltransferase/fisiologia , Dieta , Inflamação/genética , Inflamação/patologia , Resistência à Insulina/genética , Macrófagos/patologia , Obesidade/genética , Esterol O-Aciltransferase/genética , Esterol O-Aciltransferase/fisiologia , Adipócitos/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Tamanho Celular , Feminino , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Inflamação/imunologia , Integrina beta1/metabolismo , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/fisiopatologia , Células RAW 264.7
15.
Pharmacogn Mag ; 13(Suppl 4): S822-S827, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29491639

RESUMO

Objective: The aim of this study was to investigate the possible herb-drug interactions between the traditional herbal formula Guibi-tang (GBT; Guipi-tang, Kihi-to) and conventional drugs. Materials and Methods: GBT was orally administered to either male or female Sprague Dawley (SD) rats once daily at doses of 1000, 2000, or 5000 mg/kg/day for 13 weeks. The messenger ribonucleic acid (mRNA) expression of drug-metabolizing enzyme cytochrome P450 isozymes (cytochrome P450s; CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) was analyzed in hepatic tissues by reverse transcription-polymerase chain reaction. Results: Repeated oral administration of GBT did not significantly influence the mRNA expression of hepatic CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1 in male rats. By contrast, in female rats, the mRNA expression of hepatic CYP1A2 and 2B1/2 was significantly increased by repeated GBT treatment. Conclusion: Our findings indicate that caution is required in females when GBT is taken concomitantly with conventional drugs metabolized by CYP1A2 or 2B1/2. Our results provide information regarding the safety and effectiveness of GBT for clinical use. SUMMARY: Repeated oral administration of Guibi-tang (GBT) for 13 weeks did not affect the messenger ribonucleic acid (mRNA) expression of hepatic CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1 in male ratsRepeated oral administration of GBT for 13 weeks induced mRNA expression of hepatic CYP1A2 and 2B1/2 but not for CYP1A1, 2C11, 2E1, 3A1, 3A2, and 4A1 in female rats. Abbreviations used: CYP450: Cytochrome P450s, GBT: Guibi-tang, SD: Sprague Dawley, HPLC: High-performance liquid chromatography, OECD: Organization for Economic Cooperation and Development, RNA: Ribonucleic acid, RT-PCR: Reverse transcription-polymerase chain reaction, GADPH: Glyceraldehyde-3-phosphate dehydrogenase.

16.
J Ethnopharmacol ; 216: 239-250, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29410309

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY: The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS: H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS: Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1ß, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS: Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Gastrite/prevenção & controle , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estômago/efeitos dos fármacos , Animais , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Estômago/microbiologia , Estômago/patologia
17.
BMC Complement Altern Med ; 18(1): 21, 2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29357857

RESUMO

BACKGROUND: Gyejibokryeong-hwan (Guizhi Fuling Wan in China), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. However, the genotoxicity of Gyejibokryeong-hwan has not yet been well established. METHODS: The present study investigated that the genotoxicity of an aqueous extract of Gyejibokryeong-hwan (GJBRHE): an in vitro chromosomal aberration test using Chinese hamster lung cells, an in vitro bacterial reverse mutation assay (Ames test) with Salmonella typhimurium and Escherichia coli strains, and an in vivo micronucleus test using ICR mouse bone marrow. RESULTS: GJBRHE with or without the S9 mix showed no genotoxicity in the Ames test up to 5000 µg/plate or in the in vivo MN test up to 2000 mg/kg body weight. In contrast, the chromosomal aberration test showed that GJBRHE induced an increase in the number of chromosomal aberrations compared with the control after treatment for 6 h with 4200 µg/mL GJBRHE in the presence of the S9 mix and for 22 h with 800 µg/mL GJBRHE in the absence of the S9 mix. CONCLUSIONS: GJBRHE did not cause detectable genotoxic effects in the bacterial mutation test or the in vivo MN test, however genotoxic effect was detected in the in vitro chromosomal aberration assay. Our results suggest that GJBRHE may be associated with a low risk of carcinogenesis. Thus, further detailed experiments would be needed to clarify the compound responsible for inducing this genotoxicity of GJBRHE and to determine its mechanism.


Assuntos
Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/toxicidade , Mutagênicos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Linhagem Celular , Cricetinae , Escherichia coli/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos
18.
BMJ Open ; 7(11): e018362, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196484

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS), known as a functional and organic gastrointestinal disorder, is a collection of symptoms that occur together and generally include pain or discomfort in the abdomen and changes in bowel movement patterns. Due to the limitations of conventional treatments, alternative IBS treatments are used by many patients worldwide. Samryungbaekchulsan (SRS), a herbal formula, has long been used for alleviating diarrhoea-predominant IBS (D-IBS) in traditional Korean medicine. Otilonium bromide (OB) is an antimuscarinic compound used to relieve spasmodic pain in the gut, especially in IBS. Although herbal formulae and Western drugs are commonly coadministered for various diseases in Korea, few clinical studies have been conducted regarding the synergic effects of these treatments for any disease, including D-IBS. METHODS AND ANALYSIS: This trial is a randomised, double-blinded, placebo-controlled, double-dummy, four-arm, parallel study. After a 2-week preparation period, 80 patients with D-IBS will be randomly assigned to one of four treatment groups consisting of SRS (water extract granules, 5 g/pack, three times a day) with OB (tablet form, one capsule three times a day) or their placebos, with treatment lasting for 8 weeks. Post-treatment follow-up will be conducted 4 weeks after the end of treatment. The primary outcome is the finding obtained using the Subject's Global Assessment of Relief method. The secondary outcomes are the severity of symptoms related to D-IBS, determined using a 10-point scale, and the change in symptoms. ETHICS AND DISSEMINATION: This trial has full ethical approval of the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS15MISV0033) and the Korean Ministry of Food and Drug Safety (30769). The results of the study will be disseminated through a peer-reviewed journal and/or conference presentations. TRIAL PROTOCOL VERSION: IS15MISV0033 version 4.0 (25 July 2016). TRIAL REGISTRATION NUMBER: KCT0001621 (approval date: 10 August 2015).


Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Antagonistas Muscarínicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Dor Abdominal/tratamento farmacológico , Protocolos Clínicos , Defecação/efeitos dos fármacos , Diarreia/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Antagonistas Muscarínicos/farmacologia , Extratos Vegetais/farmacologia , Compostos de Amônio Quaternário/farmacologia , República da Coreia
19.
Mol Metab ; 6(8): 863-872, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28752050

RESUMO

OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion. METHODS: We examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors. RESULTS: Adipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity. CONCLUSIONS: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in patients.


Assuntos
Adipocinas/sangue , Ácidos Graxos/metabolismo , Neurregulinas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Glucose/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurregulinas/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia
20.
Iran J Pharm Res ; 16(Suppl): 197-206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29844791

RESUMO

Dendrobium genus was reported to contain alkaloid, bibenzyl, fluorenone, phenanthrene, sesquiterpenoid, and phenolic acid, which have biological properties. Our aim was to investigate the protective effect of an aqueous extract of Dendrobium nobile Lindl (DNE) against cisplatin-induced acute kidney injury (AKI). Quantification of four phenolic acids (4-hydroxybenzoic, vanillic, syringic, and ferulic acid) in DNE was determined using the HPLC-photodiode array method. Possible protective effects against cisplatin-induced nephrotoxicity were investigated using in-vitro (porcine kidney cells; PK15) and in-vivo (Sprague Dawley rat) studies. Among the four phenolic acids, 4-hydroxybenzoic acid was the most abundant. In the in-vitro study, DNE pretreatment partially prevented decrement of viability after cisplatin (15 µg/mL) treatment in the both the MTT and crystal violet assays. Moreover, relative to cells treated with cisplatin alone, the DNE (50 µg/mL)-pretreated cells showed a ~30% increase in glutathione levels and a ~15% decrease in reactive oxygen species. The expression of p53 was also decreased in DNE-pretreated cells (p < 0.05). In the in-vivo study, the renal function index decreased to normal levels in groups pretreated with DNE (300 and 500 mg/kg); histopathological alterations and apoptotic cells were also attenuated. Moreover, DNE pretreatment ameliorated oxidative stress in the kidney, as evidenced by recovered antioxidant enzyme levels and decreased lipid peroxidation. DNE, by decreasing oxidative stress, was found to have a protective effect against cisplatin-induced nephrotoxicity. Based on these findings, DNE might be beneficial when treating cisplatin-induced AKI.

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