RESUMO
Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17α-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4-7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.
Assuntos
Diterpenos do Tipo Caurano , Diterpenos , Inula , Sesquiterpenos , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Diterpenos do Tipo Caurano/química , Inula/química , Estrutura Molecular , Componentes Aéreos da Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.
Assuntos
Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/patologia , Esôfago/patologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Ácido Clorídrico/farmacologia , Remodelação das Vias Aéreas/fisiologia , Animais , Hiper-Reatividade Brônquica/metabolismo , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Modelos Animais de Doenças , Esôfago/metabolismo , Refluxo Gastroesofágico/induzido quimicamente , Cobaias , Masculino , Pneumonia/etiologia , Pneumonia/metabolismo , Pneumonia/patologia , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Transdução de Sinais/fisiologia , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
OBJECTIVE: To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism. METHODS: PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot. RESULTS: At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin. CONCLUSION: Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.
Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Rotenona/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Rotenona/farmacologiaRESUMO
BACKGROUND: Mental stress is an important risk factor for gastroesophageal reflux disease (GERD), which interacts with acid reflux and affects the efficacy of single acid suppression treatment. However, the specific mechanism remains elusive, and there is a lack of available models for further support. METHODS: This study established a new compound model combining acid reflux and chronic unpredictable mild stress (CUMS) to observe potential peripheral and central pathophysiological changes. KEY RESULTS: Rats in the compound model suffered from significant weight loss and manifested depression-like behaviours. In addition, the acid reflux was not aggravated despite the presence of mental stress, along with dilated intercellular space (DIS), increased expression of desmoglein-1 (DSG1) mRNA, and injury of the lower oesophageal mucosa. The balance between pro-inflammatory and anti-inflammatory factors was disrupted. In the hypothalamus of rats in the compound model, the expression of corticosterone-releasing factor (CRF) and its receptors, protein kinase A (PKA), and γ-aminobutyric acid (GABA) receptors were decreased. This might be related to the "escape" of stress, which weakened the suppressive effect on excitatory transmission to cope with the damage of pressure to the body. CONCLUSIONS & INFERENCES: Mental stress and acid reflux affect GERD through peripheral and central aspects, which can result in the poor efficacy of acid inhibitors. This may provide a new direction for the treatment of GERD.
Assuntos
Esofagite Péptica , Refluxo Gastroesofágico , Animais , Mucosa Esofágica/metabolismo , Refluxo Gastroesofágico/complicações , Azia , RatosRESUMO
Background: This study aimed to explore the clinical efficacy of Chaihu Shugan powder combined with Zu San Li acupoint stimulation on the acute pancreatitis of liver and qi stagnation syndromes, the protection of intestinal barrier function, the prevention of severe tendency, and safety evaluation. Method: Data were collected from October 2019-June 2021 at Xinhua Hospital, which is affiliated with Shanghai Jiao Tong University School of Medicine, Emergency Department. Eighty patients with acute pancreatitis were randomly divided into a control treatment group (40 people) and a combined traditional Chinese medicine (TCM) treatment group (40 people). Detailed records of hospitalised patients were obtained, including the general situation of patients' clinical diagnosis and clinical examination before and after treatment. The changes in inflammatory and immune indexes before and after treatment were recorded. Result: Compared with the standard treatment group, the relief time of abdominal pain in the TCM treatment group was significantly shortened with statistically significant differences. Compared with the standard treatment group, the levels of WBC, ALT, CA, hemodiastase, lipase, TG, and other factors in the TCM treatment group decreased, whereas the levels of DB, SCR, cholesterol, K+, and other factors increased. The differences were statistically significant (P < 0.05). Conclusion: Chaihu Shugan powder combined with Zu San Li acupoint stimulation can reduce the clinical manifestations of liver and qi stagnation syndromes of acute pancreatitis, protect the intestinal barrier function, prevent the tendency of severe illness and improve the prognosis.
RESUMO
The purpose of this research was to prepare floating calcium alginate beads of berberine for targeting the gastric mucosa and prolonging their gastric residence time. The floating beads were prepared by suspending octodecanol and berberine in sodium alginate (SA) solution. The suspension was then dripped into a solution of calcium chloride. The hydrophobic and low-density octodecanol enhanced the sustained-release properties and floating ability of the beads. The bead formulation was optimized for different weight ratios of octodecanol and SA and evaluated in terms of diameter, floating ability and drug loading, entrapment and release. In vitro release studies showed that the floating and sustained release time were effectively increased in gastric media by addition of octodecanol. In vivo studies with rats showed that a significant increase in gastric residence time of beads had been achieved.
Assuntos
Alginatos/síntese química , Berberina/síntese química , Berberina/farmacologia , Sistemas de Liberação de Medicamentos , Microesferas , Estômago/efeitos dos fármacos , Animais , Berberina/administração & dosagem , Géis , Masculino , Especificidade de Órgãos/efeitos dos fármacos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Solubilidade/efeitos dos fármacos , Fatores de TempoRESUMO
OBJECTIVE: To compare the characteristics of the traditional Chinese medicine (TCM) syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with reflux esophagitis (RE), in terms of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and helicobacter pylori (HP) infection. METHODS: Patients with RE were enrolled from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from June 2007 to December 2009 and patients exhibiting the syndrome of gallbladder heat attacking the stomach or stagnant heat of the liver and stomach were collected. The patients were requested to complete clinical questionnaires. The general data, characteristics of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and HP infection of the two patterns were compared. RESULTS: The average age of the selected patients with gallbladder heat attacking the stomach was older than that of the patients with stagnant heat of the liver and stomach (P<0.01) and the accompanying clinical signs and symptoms were more severe (P<0.01). The incidence of gallbladder diseases in patients with gallbladder heat attacking the stomach was higher than that of the patients with stagnant heat of the liver and stomach (P<0.01). The extent of the esophageal mucosal inflammation under endoscopy as well as the gastric bile reflux and the incidence of HP infection was also more severe (P<0.01). CONCLUSION: There are significant differences in several regards between the syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with RE. These characteristics may provide sound evidence for differentiation of signs and symptoms for this disease.
Assuntos
Esofagite Péptica/diagnóstico , Medicina Tradicional Chinesa , Adulto , Idoso , Idoso de 80 Anos ou mais , Refluxo Biliar/diagnóstico , Feminino , Refluxo Gastroesofágico/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
A phytochemical study performed on Inula japonica led to isolation of a new 1,10-seco-sesquiterpene dimer Neolinulicin A (1) and 1,10-seco-sesquiterpene Neolinulicin B (2), together with nine known sesquiterpenes (3-11). Among them, Neolinulicin A (1), which has a new carbon skeleton, was a Diels-Alder [4 + 2] adduct of two sesquiterpene moieties. Their structures were established by extensive spectroscopic analysis. All of the isolated compounds showed inhibition of NO production in RAW 264.7 macrophages. The findings might supply information for the future design of anti-inflammatory agents from I. japonica.
Assuntos
Anti-Inflamatórios/farmacologia , Inula/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , China , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Células RAW 264.7 , Sesquiterpenos/isolamento & purificaçãoRESUMO
To investigate the role played by gut microbiota in the development and treatment of acute pancreatitis. Gut microbiota is the largest micro-ecosystem in the human body, and is related to various system diseases. Acute pancreatitis is one of the common acute critical diseases in clinical practice, and there are various causative factors for the occurrence of this disease, such as alcohol, infection, obstruction and intestinal microecological factors. The dysbiosis of gut microbiota may play an important role in the pathogenesis of acute pancreatitis and affect prognoses, including gut microbiota structure disorder and bacterial translocation. It can also affect host metabolism and increase the production of toxic metabolites and affect the treatment of acute pancreatitis. Probiotics are live microorganisms that can give health benefits to the host when applied in sufficient quantities, which can effectively stimulate the growth and reproduction of the normal flora of the body, inhibit the overgrowth of pathogenic bacteria, and have a protective effect on the intestinal barrier function. A search of electronic databases (PubMed, EMBASE, Cochrane) has been realized to summarize the information. The paper briefly describes the concept of gut microbiota and acute pancreatitis, examines the role of gut microbiota in the development and treatment of acute pancreatitis, concludes the investigations of the therapeutic effect of probiotics for dysbiosis of gut microbiota in acute pancreatitis in order to provide a valid reference for the development of subsequent clinical strategies.
Assuntos
Microbioma Gastrointestinal , Pancreatite , Doença Aguda , Disbiose/terapia , Ecossistema , Humanos , Pancreatite/terapiaRESUMO
BACKGROUND: To analyze the rule of traditional Chinese medicine in the treatment of acute pancreatitis (AP). METHODS: Using machine learning technology and artificial intelligence, we collected 516 traditional Chinese medicine compounds for treating AP in the recent past 20 years, and analyzed the application of Chinese medicine in the field of AP. The data set was established by the ingredients of each prescription and its corresponding effectiveness. 90% of the data was divided into the training set, and the remaining 10% of the data was used as the test set. We employed random forest method to build a model to predict the efficacy of the prescriptions in the treatment of AP. The R-squared score and mean absolute error was used to evaluate the model's performance. RESULTS: The most frequently used drugs were rhubarb, Radix Bupleuri, Fructus Aurantii Immaturus, and Mirabilite. Rhubarb and Rhizoma Corydalis had the greatest curative effect. The random forest model that fit all data showed that its R-squared score reached 0.8021. And the results predicted on the test set showed that the R-squared score reached 0.7318. CONCLUSIONS: Soothing the liver, promoting qi, clearing heat, removing obstructions of organs, activating blood, and resolving stagnation are the treatment methods for AP.
Assuntos
Medicina Tradicional Chinesa , Pancreatite , Doença Aguda , Inteligência Artificial , Humanos , Aprendizado de Máquina , Pancreatite/tratamento farmacológico , TecnologiaRESUMO
OBJECTIVE: To screen and optimize the extraction of Dingxiangjiangqi granules. METHOD: The extraction route was screened by using pharmacodynamic experiment and the extraction conditions were optimized by orthogonal design and taking extract yield, content of naringin and tetrahydropalmatine as indexes. RESULT: The pharmacodynamic result showed that aqueous extract had the best effect to cure the esophagitis of rats and the optimized extraction technique was adding 12 times water, extracting 0. 5 hour for 3 times. CONCLUSION: The optimum extraction was simple, reasonable, stable and useful for further development.