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CONTEXT: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with respiratory symptoms and narrowing of airways. Gyeji-tang (GJT) is a traditional Asian medicine that has been used to relieve early-stage cold symptoms, headache, and chills. OBJECTIVE: We examined the effect and potential molecular action mechanism of GJT in a mouse model of COPD induced by cigarette smoke (CS) plus lipopolysaccharide (LPS). MATERIALS AND METHODS: COPD was induced in C57BL/6J mice via daily exposure to CS for 1 h for 8 weeks and intranasal administration of LPS on weeks 1, 3, 5, and 7. GJT (100 or 200 mg/kg) or roflumilast (5 mg/kg) was administrated daily for the final 4 weeks of COPD induction. RESULTS: Administration of GJT significantly suppressed the CS/LPS-induced increases in: the numbers of total cells and macrophages in bronchoalveolar lavage fluid; the expression levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1ß, and IL-8; the activities (phosphorylation) of nuclear factor kappa B and signal transducer and activator of transcription 3; and the expression levels of the structural remodelling markers, transforming growth factor beta, matrix metallopeptidase (MMP)-7, and MMP-9. DISCUSSION AND CONCLUSIONS: These results demonstrate that GJT prevents the lung inflammation and airway remodelling induced by CS plus LPS exposure in mice, suggesting that GJT may have therapeutic potential for the treatment of COPD.
Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Fator de Transcrição STAT3/metabolismo , NF-kappa B/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Interleucina-8/uso terapêutico , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Pulmão , Nicotiana , Modelos Animais de Doenças , Anti-Inflamatórios/uso terapêutico , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) refers to a lung disorder associated with symptoms of dyspnea, cough, and sputum production. Traditionally, Yijin-tang (YJT), a mixture of Pinellia ternate, Poria cocos, ginger, Chinese liquorice, and tangerine peel, has been prescribed for the treatment of respiratory system diseases caused by dampness phlegm. This experiment investigated the therapeutic effect of YJT in a mouse model of cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD. METHODS: COPD was induced by exposing mice to CS for 1 hour per day for 8 weeks, with intranasal delivery of LPS on weeks 1, 3, 5, and 7. YJT was administered at doses of 100 and 200 mg/kg 1 hour before CS exposure for the last 4 weeks. RESULTS: YJT significantly suppressed CS- and LPS-induced increases in inflammatory cell counts and reduced interleukin-1 beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels in bronchoalveolar lavage fluid (BALF) and lung tissue. In addition, YJT not only decreased airway wall thickness, average alveolar intercept, and lung fibrosis, but it also suppressed the expression of matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-B (TGF-ß) and collagen deposition. Moreover, YJT suppressed phosphorylation of nuclear factor-kappa B (NF-κB) as well as expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). CONCLUSION: Collectively, our findings show that YJT attenuates respiratory inflammation and airway remodeling caused by CS and LPS exposure; therefore, therapeutic applications in COPD can be considered.
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BACKGROUND: Palmijihwanghwan (PJH) is a traditional medicine and eight constituents derived from PJH possess anti-inflammatory activities. However, the scientific evidence for its potential as a therapeutic agent for inflammatory lung disease has not yet been studied. In this study, we examined the protective effect of PJH in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) with lipopolysaccharide (LPS). METHODS: Mice received CS exposure for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. PJH (100 and 200 mg/kg) was administrated daily 1 h before CS treatment for the last 4 weeks. RESULTS: Compared with CS plus LPS-exposed mice, mice in the PJH-treated group showed significantly decreased inflammatory cells count and reduced inflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6 and tumor necrosis factor alpha (TNF-α) levels in broncho-alveolar lavage fluid (BALF) and lung tissue. PJH also suppressed the phosphorylation of nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) caused by CS plus LPS exposure. Furthermore, CS plus LPS induced increases in matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-ß (TGF-ß) expression and collagen deposition that were inhibited in PJH-treated mice. CONCLUSIONS: This study demonstrates that PJH prevents respiratory inflammation and airway remodeling caused by CS with LPS exposure suggesting potential therapy for the treatment of COPD.
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Anti-Inflamatórios/farmacologia , Medicina Tradicional Chinesa/métodos , Extratos Vegetais/farmacologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/etiologia , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
The flavonoid myricetin is abundant in vegetables and has various bioactive properties, including anti-inflammatory and antioxidative activities. In the present study, we explored the effects of myricetin on alcohol-induced gastric ulcer in a rat model. To induce gastric ulcer, absolute ethanol (5 mL/kg body weight) was orally administrated to each rat. The positive control and myricetin-treated groups were given oral doses of omeprazole (20 mg/kg) or myricetin (12 mg/kg), respectively, 1 hour prior to the administration of absolute alcohol. We found that pretreatment with myricetin significantly decreased alcohol-induced gastric ulcer, hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Myricetin pretreatment reduced the level of malondialdehyde (MDA) and increased that of total glutathione (GSSG/GSH) and superoxide dismutase (SOD) in gastric tissues. In addition, it elevated the expression levels of cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) and decreased the phosphorylation of nuclear factor kappa B (NF-κB). Together, these results indicate that myricetin effectively inhibits ethanol-induced acute gastric injury by preventing oxidative damage, stimulating PGE2 production, and inhibiting NF-κB activation. We suggest that myricetin may be an alternative treatment for gastric injury caused by alcohol intake.
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ETHNOPHARMACOLOGICAL RELEVANCE: Asteris Radix et Rhizoma (AR) refers to the roots and rhizomes of Aster tataricus L., which is widely distributed throughout East Asia. AR has been consumed as a traditional medicine in Korea, Japan and China for the treatment of urologic symptoms. To date, however, the therapeutic effect of AR on benign prostatic hyperplasia (BPH) has not been investigated. AIM OF THE STUDY: The present study evaluated the therapeutic effects of AR on a testosterone-induced BPH rats. MATERIALS AND METHODS: We induced BPH to rats by subcutaneous injections (s.c) of testosterone propionate (TP) daily for four weeks. Rats were also administered daily oral gavage of AR (150 mg/kg) or vehicle. After four weeks of induction, all animals were euthanized humanely and their prostate glands were removed, weighed and processed for further analysis, including histopathological examination, real-time PCR, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Western blot analysis. RESULTS: Administration of AR to TP-induced BPH rats considerably reduced prostate weight and concentrations of serum testosterone and prostate dihydrotestosterone (DHT). Epithelial thickness and expression of proliferating cell nuclear antigen (PCNA) were markedly suppressed by AR-treatment in the rats. Furthermore, the expression of the B-cell lymphoma 2 (Bcl-2) were reduced and expression of the Bcl-2-associated X protein (Bax) increased, resulting in significant reduction in Bcl-2/Bax ratio. In addition, AR decreased the level of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were reduced by AR treatment in a TP-induced BPH rat model. CONCLUSIONS: AR alleviates BPH by promoting apoptosis and suppressing inflammation, indicating that AR may be used clinically to treat BPH accompanied by inflammation.
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Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Aster , Extratos Vegetais/farmacologia , Raízes de Plantas , Próstata/efeitos dos fármacos , Hiperplasia Prostática/prevenção & controle , Rizoma , Propionato de Testosterona , Animais , Anti-Inflamatórios/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Aster/química , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Tamanho do Órgão , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Rizoma/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UMH), of the family Ulmaceae, is a deciduous tree, widely distributed throughout Korea. UMH has been used as a traditional oriental medicine in Korea for the treatment of urological disorders, including bladder outlet obstruction (BOO), lower urinary tract syndrome (LUTS), diuresis, and hematuria. To date, its possible protective effects against benign prostatic hyperplasia (BPH) have not been analyzed. AIM OF THE STUDY: This study investigated the effects of UMH on the development of BPH using a rat model of testosterone propionate (TP)-induced BPH. MATERIALS AND METHODS: BPH was induced by daily subcutaneous injections of testosterone propionate (TP) for four weeks. UMH was administrated daily by oral gavage at a dose of 150â¯mg/kg during the four weeks of TP injections. Animals were sacrificed, and their prostates were weighed and subjected to histopathological examination, TUNEL assay, and western blot analysis. RESULTS: Treatment of BPH-model rats with UMH significantly reduced prostate weight, serum testosterone concentration and dihydrotestosterone (DHT) concentration in prostate tissue. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) were significantly attenuated in UMH-treated rats. In addition, UMH administration markedly induced the activation of caspases-3, -â¯8, and -â¯9 in prostate tissues of BPH rats, accompanied by upregulation of expression of Fas, Fas-associated protein with death domain (FADD), and Fas ligand (FasL) and a reduction in the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2-associated X protein (Bax). CONCLUSIONS: UMH effectively inhibited the proliferation and promoted the apoptosis of prostate cells, suggesting it may be useful for the treatment of BPH.