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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.
J Ethnopharmacol ; 255: 112779, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32209388

RESUMO

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.

3.
J Ethnopharmacol ; 235: 406-414, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30703490

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lithospermi radix has been prescribed in traditional folk medicine to treat diverse diseases like cancer. AIM OF THE STUDY: The present study assessed the sub-chronic oral toxicity of an aqueous extract of lithospermi radix (WLR) in Fischer 344 rats over a period of 13 weeks. MATERIALS AND METHODS: The chemical compositions of WLR were analyzed using ultra-high performance liquid chromatography (UHPLC). WLR was daily administered to Fischer 344 rats at 0, 500, 1000, and 2000 mg/kg body weights (bw) for 13 weeks via oral gavage. Changes in mortalities, body weights, and intakes of food and water were monitored during the WLR treatment period. Urine was collected and analyzed 12 h before necropsy. Organ weights, hematological parameters, and plasma biochemical parameters were determined along with histopathological examination. RESULTS: When compared with the normal control group, no remarkable toxic signs or parameter variations related with WLR treatment were observed in mortality, body weights, organ weights, food and water consumptions, urinalysis, hematological and plasma biochemical analyses, and histopathological examination. Mortalities observed in one male at 2000 mg/kg bw and three females at 1000 mg/kg bw were not related with WLR treatment because no gross findings of toxicity were observed in both morphological and histological examination. Some significant changes in clinical parameters or histological lesions observed in WLR-treated animals were not related with WLR treatment because the differences were marginal and did not show dose-dependent or directional changes. CONCLUSIONS: Based on these findings, the calculated no-observed-adverse-effect-level (NOAEL) in rats was higher than 2000 mg/kg bw.


Assuntos
Lithospermum/química , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/toxicidade , Testes de Toxicidade Subcrônica , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Masculino , Medicina Tradicional , Nível de Efeito Adverso não Observado , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Ratos , Ratos Endogâmicos F344
4.
Biol Pharm Bull ; 42(1): 1-9, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30381617

RESUMO

Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.


Assuntos
Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Propionato de Testosterona/toxicidade , Veratrum , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
5.
J Ethnopharmacol ; 233: 115-122, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30508623

RESUMO

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 150 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, - 8, and - 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.


Assuntos
Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Ulmus , Animais , Apoptose/efeitos dos fármacos , Di-Hidrotestosterona/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Próstata/patologia , Próstata/fisiologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Testosterona/sangue , Propionato de Testosterona
6.
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
7.
Biol Pharm Bull ; 40(12): 2125-2133, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28943529

RESUMO

Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3ß (GSK3ß) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combretaceae/química , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Animais , Di-Hidrotestosterona/sangue , Humanos , Masculino , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação , Próstata/citologia , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Sementes/química , Testosterona/sangue , Testosterona/metabolismo , Propionato de Testosterona/toxicidade
8.
Int Immunopharmacol ; 49: 67-76, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28551494

RESUMO

Isoimperatorin (IMP), an active natural furocoumarin, has numerous pharmacologic effects, including anti-inflammatory, analgesic, antispasmodic, and anticancer activities. This study aimed to evaluate the preventive activity of IMP in an ovalbumin (OVA)-induced murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice were sensitized on days 0 and 14 via intraperitoneal injection of 20µg OVA. On days 21-23 after the initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1h; meanwhile, IMP (10 or 30mg/kg once daily) was administered by gavage on days 18-23. Our results revealed that IMP significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, eotaxin, and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that IMP inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. In addition, pretreatment with IMP suppressed the activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular-signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-κB (NF-κB). Together, these results suggest that IMP effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of Th2 cytokines and inhibiting NF-κB and MAPK pathways.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Furocumarinas/uso terapêutico , Pneumonia/tratamento farmacológico , Células Th2/imunologia , Alérgenos/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Muco/metabolismo , NF-kappa B/metabolismo , Ovalbumina/imunologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Ann Rehabil Med ; 41(6): 961-968, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29354572

RESUMO

Objective: To prospectively assess the association between impoverished sensorimotor integration of the tongue and lips and post-extubation dysphagia (PED). Methods: This cross-sectional study included non-neurologic critically ill adult patients who required endotracheal intubation and underwent videofluoroscopic swallowing study (VFSS) between October and December 2016. Participants underwent evaluation for tongue and lip performance, and oral somatosensory function. Demographic and clinical data were retrieved from medical records. Results: Nineteen patients without a definite cause of dysphagia were divided into the non-dysphagia (n=6) and the PED (n=13) groups based on VFSS findings. Patients with PED exhibited greater mean duration of intubation (11.85±3.72 days) and length of stay in the intensive care unit (LOS-ICU; 13.69±3.40 days) than those without PED (6.83±5.12 days and 9.50±5.96 days; p=0.02 and p=0.04, respectively). The PED group exhibited greater incidence of pneumonia, higher videofluoroscopy swallow study dysphagia scale score, higher oral transit time, and lower tongue power and endurance and lip strength than the non-dysphagia groups. The differences in two-point discrimination and sensations of light touch and taste among the two groups were insignificant. Patients intubated for more than 7 days exhibited lower maximal tongue power and tongue endurance than those intubated for less than a week. Conclusion: Duration of endotracheal intubation, LOS-ICU, and oromotor degradation were associated with PED development. Oromotor degradation was associated with the severity of dysphagia. Bedside oral performance evaluation might help identify patients who might experience post-extubation swallowing difficulty.

10.
Ann Rehabil Med ; 40(2): 206-13, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27152269

RESUMO

OBJECTIVE: To examine the characteristics and changes in the pharyngeal phase of swallowing according to fluid viscosity in normal healthy persons, to help determine fluid intake methods in more detail than the use of standardized fluid. METHODS: This was a prospective observational study involving 10 normal healthy adults. While the participants sequentially took in fluids with 10 different viscosities changes in the pharyngeal phase of the swallowing process were monitored using videofluoroscopic swallowing studies (VFSS). Twenty parameters of the pharyngeal phase, including epiglottis contact, laryngeal elevation, pharyngeal constriction, and upper esophageal sphincter opening, were determined and compared. RESULTS: No significant viscosity-based changes in epiglottis contact, laryngeal elevation, or upper esophageal sphincter-opening duration of the pharyngeal phase were observed. However, pharyngeal transit time and time from the start of the pharyngeal phase to peak pharyngeal constriction were significantly delayed upon intake of fluid with viscosities of 150.0 centipoise (cP) and 200.0 cP. CONCLUSION: VFSS analysis of fluid intake may require the use of fluids of various concentrations to determine a suitable viscosity of thickener mixture for each subject.

11.
AJR Am J Roentgenol ; 185(3): 661-7, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16120914

RESUMO

OBJECTIVE: Our purposes were to determine whether a single application of radiofrequency energy to normal bone can create coagulation necrosis reproducibly and to assess the accuracy of MRI at revealing the extent of radiofrequency-induced thermal bone injury. MATERIALS AND METHODS: Using a 200-W generator and a 17-gauge cooled-tip electrode, a total of 11 radiofrequency ablations were performed under fluoroscopic guidance in the distal femurs of seven dogs. Radiofrequency was applied in standard monopolar mode at 100 W for 10 min. During radiofrequency ablation, the changes in impedance and currents were recorded. MRI, including unenhanced T1- and T2-weighted images and contrast-enhanced fat-suppressed T1-weighted images, was performed to evaluate ablation regions. Six dogs were killed on day 4 after MRI and one dog on day 7. RESULTS: In all animals, radiofrequency ablation created a well-defined coagulation necrosis and no significant complications were noted. The mean long-axis diameter and the mean short-axis diameter of the coagulation zones produced were 45.9 +/- 5.5 mm and 17.7 +/- 2.7 mm, respectively. At gross examination, thermal ablation regions appeared as a central, light-brown area with a dark-brown peripheral hemorrhagic zone, which was surrounded by a pale-yellow rim. On MRI, the ablated areas showed multilayered zones with signal intensities that differed from normal marrow on unenhanced images and a perfusion defect on contrast-enhanced T1-weighted images. The maximum difference between lesion sizes on MR images, established by measuring macroscopic coagulation necrosis, was 3 mm. The correlation between the diameter of coagulation necrosis and lesion size at MRI was strong, with correlation coefficients ranging from 0.89 for unenhanced T1-weighted images and 0.97 for unenhanced T2-weighted images to 0.98 for contrast-enhanced T1-weighted images (p < 0.05). CONCLUSION: Radiofrequency ablation created well-defined coagulation necrosis in a reproducible manner, and MRI accurately determined the extent of the radiofrequency-induced thermal bone injury.


Assuntos
Ablação por Cateter , Fêmur/lesões , Fêmur/cirurgia , Imagem por Ressonância Magnética/métodos , Animais , Cães , Feminino , Fluoroscopia , Necrose , Reprodutibilidade dos Testes
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