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1.
Artigo em Inglês | MEDLINE | ID: mdl-36644440

RESUMO

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

2.
Eur J Pharmacol ; 928: 174976, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35487253

RESUMO

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Animais , Claritromicina/metabolismo , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Etanol/farmacologia , Mucosa Gástrica , Gastrite/tratamento farmacológico , Gastrite/prevenção & controle , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Octreotida/farmacologia , Octreotida/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico
3.
Comb Chem High Throughput Screen ; 25(8): 1294-1303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34053424

RESUMO

AIMS AND OBJECTIVES: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. MATERIALS AND METHODS: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. RESULTS: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. CONCLUSION: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.


Assuntos
Dendrobium , Hiperuricemia , Trifosfato de Adenosina/metabolismo , Animais , Frutose , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Rim/metabolismo , Ácido Oxônico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ácido Úrico , Xantina Oxidase
4.
J Pharm Biomed Anal ; 138: 134-141, 2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28196345

RESUMO

Ophiopogon japonicus (Linn. f.) Ker-Gawl (O. japonicas), mainly cultivated in Sichuan and Zhejiang province in China, has different bioactive components and therefore their pharmacological activities. To explain the different clinical efficacy of O. japonicas derived preparations, herein we report differences of pharmacological activities between Sichuan and Zhejiang O. japonicas and behind them the exact differences of bioactive components. Based on a LC/MS-IT-TOF method, the differences of bioactive components between Sichuan and Zhejiang O. japonicas extracts were analyzed and respective characteristic components were picked out. We determined 39 ophiopogonones and 71 ophiopogonins compounds in Sichuan and Zhejiang O. japonicas extracts and found the contents of these compositions have several times difference. Evidenced by experimental data of pharmacological activities in inhibiting cardiomyocyte damage induced by H2O2, mouse macrophage cell inflammation induced by lipopolysaccharide and cytotoxicity in vitro, Zhejiang O. japonicas extract had a stronger antioxidant and anti-inflammatory capacity than Sichuan O. japonicas extract, and the two O. japonicas extracts exhibited selective cytotoxicity on different cancer cell lines in vitro. These data shed light on the links between bioactive components and pharmacological activities of O. japonicas derived preparations. Thus, geographical origin of O. japonicas should be considered to be a key factor in efficacy studies and further clinical application.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ophiopogon/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células A549 , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , China , Células HCT116 , Células HT29 , Células Hep G2 , Humanos , Células MCF-7 , Ratos
5.
Obes Surg ; 26(1): 91-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25982806

RESUMO

BACKGROUND: The aim is to evaluate via meta-analysis bone metabolism and bone mineral density (BMD) in morbidly obese patients before and after bariatric surgery. METHODS: We searched Medline, EMBASE, and the Cochrane Library for relevant studies published before January 2014. The following outcomes were evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25-hydroxyvitamin D [25(OH)D], serum or urinary N-telopeptide (NTX), bone-specific alkaline phosphatase (BSAP), and bone mineral density (BMD). RESULTS: Ten studies, including 344 patients, met our inclusion criteria. Results showed a significant decrease in serum calcium (MD = -0.10, 95 %CI -0.14 to -0.07, P < 0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31, P < 0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI -1.12 to 3.83, P = 0.28) following bariatric surgery. There were significant increases in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66, P = 0.02) and BSAP (MD = 7.47, 95 %CI 0.21 to 14.72, P = 0.04) but a significant decrease in BMD (MD = -0.08, 95 %CI -0.13 to -0.04, P < 0.00001) after bariatric surgery. CONCLUSION: BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery. Basal bone metabolism should be evaluated preoperatively. To prevent secondary hyperparathyroidism and bone loss, calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.


Assuntos
Cirurgia Bariátrica , Densidade Óssea , Remodelação Óssea , Fosfatase Alcalina/sangue , Fosfatase Alcalina/urina , Cálcio/sangue , Colágeno Tipo I/sangue , Colágeno Tipo I/urina , Humanos , Obesidade Mórbida/cirurgia , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Peptídeos/urina , Vitamina D/análogos & derivados , Vitamina D/sangue
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