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1.
Curr Treat Options Oncol ; 24(12): 1852-1869, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38079061

RESUMO

OPINION STATEMENT: Pancreatic cancer (PC) remains the deadliest cancer worldwide. Most patients are diagnosed at the advanced or metastatic stage, leading to a poor prognosis. Awareness of the limitations of current therapy and accompanying pain, depression, malnutrition, and side effects of chemoradiotherapy may lead patients and physicians towards complementary and alternative medicine (CAM). CAM refers to a diverse set of medical and healthcare practices, products, and systems that are not part of conventional Western medicine. Despite the low-quality evidence supporting the efficacy of these methods, they remain appealing due to patients' beliefs, fear of death, and the slow development of conventional therapy. Hence, the possibility of using natural products for pancreatic cancer is increasing. CAM options such as: medical cannabis, plants, fungi, herbal formulas, and injections, which originate primarily from traditional Chinese or Japanese medicine i.e. Curcuma longa, Panax ginseng, Poria cocos, Hochuekkito, Juzentaihoto, and Rikkunshito, Shi-quan-da-bu-tang/TJ-48, Huang-qin-tang, Shuangbai San, Wen Jing Zhi Tong Fang, Xiang-Sha-Liu-jun-zi-tang, Aidi injection, Brucea javanica oil emulsion/Yadanziyouru injection, Compound Kushen injection, Huachansu injection, Kangai injection and Kanglaite injections are becoming promising candidates for the management of pancreatic cancer. The abovementioned substances/medications are the most popular or potentially effective in PC treatment and consequently CAM-based adjuvant therapy through improving patients' quality of life, might be a useful addition in the treatment of pancreatic cancer patients.


Assuntos
Antineoplásicos , Terapias Complementares , Medicamentos de Ervas Chinesas , Neoplasias Pancreáticas , Humanos , Qualidade de Vida , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Quimiorradioterapia
2.
Food Funct ; 13(21): 10994-11007, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36239291

RESUMO

Natural polyphenols are plant metabolites exhibiting a broad range of biological activities. Among them, anticancer properties seem to be very desirable. This study examined the anticancer and anti-metastatic properties of the polyphenol-rich extract from the evening primrose seeds (EPE). In vitro and in vivo studies performed in colorectal cancer (CRC) cell lines and AOM-DSS-induced colitis-associated colon cancer in mice revealed the EPE anticancer properties. Furthermore, we studied the EPE activity on metastatic abilities and showed that the EPE inhibited invasiveness in the following models (cells isolated from patients with different invasive stages and cells with induced invasion by either Snail overexpression or CAF stimulation). More importantly, we also demonstrated that the EPE decreases the cell invasiveness of 5-fluorouracil (5-FU) resistant CRC cells. The inhibition of metastasis correlated with a decrease in thymidylate synthetase (TYMS), which has recently been associated with metastatic phenotype development. Our results indicate that the EPE might be an effective anticancer agent in suppressing colon cancer metastasis regardless of the invasiveness cause. Based on these findings, we concluded that the used EPE extract rich in polyphenols inhibits cell invasion by TYMS downregulation.


Assuntos
Neoplasias do Colo , Oenothera biennis , Camundongos , Animais , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , Oenothera biennis/metabolismo , Polifenóis/farmacologia , Fluoruracila/farmacologia , Neoplasias do Colo/tratamento farmacológico , Extratos Vegetais/farmacologia
3.
Pharmacol Rep ; 74(6): 1198-1207, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36166147

RESUMO

The novel coronavirus disease (COVID-19) still remains a major challenge to the health-care systems worldwide, inciting ongoing search for pharmaceutical and non-pharmaceutical interventions which could benefit patients already infected with SARS-CoV-2 or at increased risk thereof. Although SARS-CoV-2 primarily affects the respiratory system, it may also infect other organs and systems, including gastrointestinal tract, where it results in microbial dysbiosis. There is an emerging understanding of the role the gut microbiota plays in maintaining immune homeostasis, both inside the gastrointestinal tract and beyond (i.e. through gut-lung and gut-brain axes). One family of compounds with recognized immunomodulatory and anti-inflammatory properties are short chain fatty acids (SCFAs). SCFAs are believed that they have a protective effect in case of gastrointestinal diseases. Moreover, they are responsible for maintaining proper intestinal barrier and they take part in relevant immune functions. This review presents mechanisms of action and potential benefits of SCFA-based probiotics and direct SCFA supplementation as a strategy to support immune function amid the COVID-19 pandemic.


Assuntos
COVID-19 , Pandemias , Humanos , SARS-CoV-2 , Ácidos Graxos Voláteis
4.
Int J Mol Sci ; 23(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35328624

RESUMO

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.


Assuntos
Microbioma Gastrointestinal , Pancreatite , Doença Aguda , Bactérias , Translocação Bacteriana , Humanos , Mucosa Intestinal/metabolismo , Pancreatite/metabolismo
5.
Int J Mol Sci ; 23(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35054907

RESUMO

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Desenvolvimento de Medicamentos , Ouro/química , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Estudos Clínicos como Assunto , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/etiologia , Neoplasias do Colo/metabolismo , Terapia Combinada , Complexos de Coordenação/uso terapêutico , Gerenciamento Clínico , Suscetibilidade a Doenças , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
6.
Nutrients ; 13(9)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34579147

RESUMO

Acute pancreatitis (AP) is an inflammatory disease that causes severe tissue damage. Ghee butter from bovine colostrum (GBBC) is a clarified butter produced by heating milk fat to 40 °C and separating the precipitating protein. As colostrum mainly contains fatty acids (FAs), immunoglobulins, maternal immune cells, and cytokines, we hypothesized that it may exert anti-inflammatory effects. We investigated the effects of GBBC on experimental AP in mice. Two intraperitoneal (ip) injections of L-arginine (8%) were given 1 h apart to generate the AP murine model. After 12 h from the first L-arginine injection, mice were divided into the following experimental groups: AP mice treated with GBBC (oral gavage (po) every 12 h) and non-treated AP mice (po vehicle every 12 h). Control animals received vehicle only. At 72 h, mice were euthanized. Histopathological examination along with myeloperoxidase (MPO) and amylase/lipase activity assays were performed. In a separate set of experiments, FFAR1 and FFAR4 antagonists were used to verify the involvement of respective receptors. Administration of GBBC decreased MPO activity in the pancreas and lungs along with the microscopical severity of AP in mice. Moreover, treatment with GBBC normalized pancreatic enzyme activity. FFAR1 and FFAR4 antagonists tended to reverse the anti-inflammatory effect of GBBC in mouse AP. Our results suggest that GBBC displays anti-inflammatory effects in the mouse model of AP, with the putative involvement of FFARs. This is the first study to show the anti-inflammatory potential of a nutritional supplement derived from GBBC.


Assuntos
Anti-Inflamatórios/farmacologia , Colostro/química , Ácidos Graxos não Esterificados/metabolismo , Ghee/análise , Pancreatite/tratamento farmacológico , Amilases/metabolismo , Animais , Anti-Inflamatórios/química , Arginina/efeitos adversos , Bovinos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação/metabolismo , Lipase/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pancreatite/metabolismo , Peroxidase/metabolismo , Gravidez , Receptores Acoplados a Proteínas G/metabolismo
7.
Mol Cell Endocrinol ; 538: 111448, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480991

RESUMO

Crohn's disease (CD) is an inflammatory bowel disease (IBD) which is characterized by chronic and relapsing inflammation of the gastrointestinal (GI) tract. The etiology of CD is unknown, but factors such as epithelial barrier dysfunction, immune system imbalance, microbiota dysbiosis and environmental influences are thought to be involved in its pathogenesis. Recent studies have shown that short chain fatty acids (SCFAs) and long chain fatty acids (LCFAs) play a vital role in pathophysiology and development of CD by various mechanisms affecting pro- and anti-inflammatory mediators, and maintaining the intestinal homeostasis and regulation of gene expression. SCFAs and LCFAs activate signaling cascades that control immune functions through interaction with cell surface free fatty acid receptors (FFARs), i.e. FFAR1, FFAR2, FFAR3, and FFAR4. This review highlights the role of fatty acids in maintenance of intestinal and immune homeostasis and supports the supplementation of fatty acids as a promising adjunctive treatment for CD.


Assuntos
Doença de Crohn/metabolismo , Ácidos Graxos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Regulação da Expressão Gênica , Homeostase , Humanos , Intestinos/metabolismo , Transdução de Sinais
8.
Pharmacol Rep ; 73(5): 1448-1456, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34383255

RESUMO

BACKGROUND: The pathogenesis of acute pancreatitis (AP) initiation and progression is still unknown, and effective treatment is limited to supportive care. Many phytochemicals have the potential to alleviate AP symptoms and may be a useful and effective supplement to standard AP treatment. The objective of the study was to examine the potential role of chlorogenic acid (CGA), a polyphenol known for anti-inflammatory effect, in the treatment of experimental AP in mice. METHODS: Two intraperitoneal (ip) injections of L-arginine (dosage 400 mg/100 g BW) were given 1 h apart to generate the AP murine model. Mice were separated into two experimental groups after 12 h from the first L-arginine injection: AP mice treated with CGA (oral gavage (po) every 12 h; 20 mg/kg BW) and non-treated AP mice (po vehicle, 5% dimethyl sulfoxide every 12 h). Every 12 h, control mice were given an equivalent volume of vehicle. At 72 h, mice were slaughtered. Histology, as well as myeloperoxidase (MPO) and amylase activity assays, were performed on pancreatic tissues. RESULTS: In murine mouse model of AP po administration of CGA decreased MPO vs. AP (40.40 ± 2.10 U vs. 7.39 ± 0.34; p < 0.001) as well as amylase activity vs. AP (1444 ± 56 mU/mL vs. 3340 ± 144 mU/mL, Fig. 2B; p < 0.001). When comparing CGA mice to AP mice, histological research demonstrated that the severity of AP was reduced following CGA treatment. CONCLUSIONS: The current study found that CGA might have anti-inflammatory effect on L-arginine-induced pancreatitis. Dietary intervention with CGA may be advised as a supportive treatment for AP, according to our findings.


Assuntos
Ácido Clorogênico/uso terapêutico , Inflamação/tratamento farmacológico , Pancreatite/tratamento farmacológico , Animais , Arginina/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pancreatite/induzido quimicamente , Peroxidase/genética , Peroxidase/metabolismo , Distribuição Aleatória
9.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809912

RESUMO

Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the major circulating metabolite. Further renal hydroxylation generates 1,25(OH)2D3, the most potent metabolite. Our aim was to examine the association between vitamin D levels, and its supplementation and pain intensity in 39 IBD patients and 33 healthy individuals. 25(OH)D3 and 1,25(OH)2D3 serum levels were measured. Each subject filled out visual analog scale (VAS) and Laitinen's pain assessment scales. Laboratory results were obtained, and disease activity was assessed. Linear regression was employed to investigate the correlation between 25(OH)D3, 1,25(OH)2D3 and pain intensity, clinical activity parameters, C-reactive protein, disease duration, and dietary habits. In IBD patients, 25(OH)D3 was increased, whereas 1,25(OH)2D3 was not. Vitamin D3 supplementation did not influence their levels. No correlation was found between pain scores, disease activity, inflammatory status, disease duration or dietary habits and both forms of vitamin D. Elevated 25(OH)D3 and normal 1,25(OH)D3 were found in IBD patients as compared to the controls. We discovered no effect from supplementation and no association between pain severity and vitamin D.

10.
Adv Nutr ; 12(2): 533-545, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33070186

RESUMO

Inflammatory bowel disease (IBD) is a group of chronic relapsing disorders whose etiology has not been fully explained. Therefore, available therapeutic approaches for IBD patients are still insufficient. Current treatment strategies are targeted to immune system dysfunctions, often associated with alternations in the microbiota, which contribute to the development of chronic intestinal inflammation. Therapeutics include anti-inflammatory drugs such as aminosalicylates and corticosteroids, immunosuppressive agents, antibiotics, and biological agents such as infliximab and vedolizumab. Auxiliary therapies involve a balanced and personalized diet, healthy lifestyle, avoiding stress, as well as dietary supplements. In this review, we discuss the use of bovine colostrum (BC) as a therapeutic agent, including its advantages and contraindications. We summarize our knowledge on well-researched BC constituents and their effects on the gastrointestinal tract as evidenced in in vitro and in vivo studies.


Assuntos
Colostro , Doenças Inflamatórias Intestinais , Animais , Anti-Inflamatórios/uso terapêutico , Bovinos , Contraindicações , Suplementos Nutricionais , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Gravidez
11.
Artigo em Inglês | MEDLINE | ID: mdl-32802139

RESUMO

This study was to explore the therapeutic effect and mechanism of the traditional Chinese medicine with the formula Da-Cheng-Qi-Tang (T-DCQT) and a modified Da-Cheng-Qi-Tang (M-DCQT) in a postoperative ileus (POI) mouse model. POI was induced via small bowel manipulation, and T-DCQT or M-DCQT was given by enema. The intestinal motility was measured with a charcoal mixture gavage. The intestinal tissues were collected for further studies by histopathological, qPCR, immunohistochemical staining, and Western blotting. Levels of inflammatory cytokines in blood were determined using a high-throughput liquid chip. We found that gastrointestinal dysfunction was alleviated after administration of either a T-DCQT or M-DCQT enema. Increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues of POI mice were reversed following treatment. IL-1α, IL-6, MIP-1ß, and IL-17 levels were significantly reduced at 24 h and 48 h following treatment, while the MCP-1 level was only observed to be reduced at 24 h after the treatment. Furthermore, compared with the T-DCQT effect, M-DCQT treatment was more effective in alleviating the increased IL-6, MIP-1ß, and IL-1α levels. So, we draw a conclusion that T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility in a POI mouse model.

12.
Int J Pharm ; 585: 119549, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32554032

RESUMO

Silver nanoparticles have been used in a range of applications and although they are already employed in medicine, there are new, promising possibilities for their utilization. We investigated the potential of silver nanoparticles obtained with the use of blackcurrant extract in vitro in the LPS-stimulated RAW264.7 macrophages and in vivo in the murine DSS-induced colitis model. The examined formulations contained particles of 95 nm (Ag95) and 213 nm (Ag213) diameter. In vitro, both formulations inhibited nitric oxide (NO) release. In vivo, the preparations alleviated colitis as evidenced by a decreased macroscopic score and myeloperoxidase activity (indicative of neutrophil infiltration). In both cases, the nanoparticles of larger diameter showed better anti-inflammatory properties. Although further tests are required, our results indicate a plausible new use of silver nanoparticles in inflammatory bowel diseases.


Assuntos
Colite/tratamento farmacológico , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Ribes , Prata/química , Tecnologia Farmacêutica/métodos , Animais , Sobrevivência Celular , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Peroxidase/metabolismo , Extratos Vegetais/administração & dosagem , Células RAW 264.7
13.
Nutrients ; 12(5)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370215

RESUMO

Ulcerative colitis belongs to inflammatory bowel diseases, which is a group of chronic disorders of the gastrointestinal tract. It is a debilitating condition with a wide range of symptoms including rectal bleeding, diarrhea, and visceral pain. Current dietary habits often lead to imbalance in n-6/n-3 polyunsaturated fatty acids (PUFA) in favor of n-6 PUFA. Recent data showed the potential anti-inflammatory advantage of n-3 PUFA. Walnut oil (WO) is rich in those fatty acids and mainly consists of linoleic and linolenic acids that may act via free fatty acids receptors (FFARs). We assessed the anti-inflammatory effect of WO in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Moreover, we examined changes in the expression of tight junction proteins (TJ), pro-inflammatory cytokines, and FFAR proteins in the inflamed mouse colon. WO improves the damage score in inflamed tissue, significantly restoring ion transport and colonic wall permeability. Inflammation caused changes in TJ, FFAR, and pro-inflammatory gene proteins expression, which WO was able to partially reverse. WO has anti-inflammatory properties; however, its exact mechanism of action remains unclear. This stems from the pleiotropic effects of n-3 PUFA ligands associated with receptor distribution and targeted signaling pathways.


Assuntos
Anti-Inflamatórios , Colite/tratamento farmacológico , Colite/metabolismo , Juglans/química , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Animais , Colo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/isolamento & purificação , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Junções Íntimas/metabolismo
14.
Naunyn Schmiedebergs Arch Pharmacol ; 393(8): 1357-1364, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32002574

RESUMO

TRPV1 are involved in the control of the gastrointestinal (GI) functions and pain sensation. Their activation induces pain but it is followed by desensitization, which in turn causes analgesia. The studies from the last two decades indicate that TRPV1 are involved in visceral hypersensitivity in the GI tract and pathogenesis of irritable bowel syndrome (IBS). Therefore, the aim of this study is to assess the action of fast desensitizing agonist of TRPV1, palvanil (N-palmitoyl-vanillamine), in the murine GI tract and on nociception to evaluate its potential application in the therapy of IBS. The effect of palvanil on smooth muscle contractility was evaluated using organ baths. The impact of palvanil on intestinal secretion was assessed in Ussing chambers. In vivo, the action of palvanil (0.1-1 mg/kg) was assessed in whole GI transit, fecal pellet output, and colonic bead expulsion tests. The antinociceptive potency of palvanil was tested in the mustard oil-induced pain test. Palvanil inhibited colonic contractions (evoked by electrical field stimulation, EFS) and decreased the ion transport in the colon stimulated with forskolin. It did not affect secretion in experiments with veratridine. In vivo, palvanil prolonged whole GI transit at all doses tested. At the lower dose tested, it accelerated colonic motility during first 60 min following injection. By contrast, at the dose of 1 mg/kg, colonic motility was inhibited. Palvanil induced antinociceptive action at all tested doses in mustard oil-induced pain test. TRPV1 fast-desensitizing compounds, i.e., palvanil, may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.


Assuntos
Dor Abdominal/prevenção & controle , Analgésicos/farmacologia , Capsaicina/análogos & derivados , Colo/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/tratamento farmacológico , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/efeitos dos fármacos , Dor Abdominal/induzido quimicamente , Dor Abdominal/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Capsaicina/farmacologia , Colo/metabolismo , Colo/fisiopatologia , Modelos Animais de Doenças , Técnicas In Vitro , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Mostardeira , Óleos de Plantas , Fatores de Tempo
15.
Curr Drug Targets ; 21(8): 792-806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31854272

RESUMO

Crohn's disease (CD) is an autoimmune disorder from the group of inflammatory bowel diseases. The etiology of CD is not clear; currently, the interaction between the genetic, immunological and environmental factors is assumed as the cause of the disease. Partial knowledge of those factors has led to the development of drugs, which control the clinical symptoms and improve the overall condition of the infected; the main objective of the modern therapeutic strategies is the induction and maintenance of remission. Among the wide range of available treatments, older generation molecules: mesalazine, corticosteroids and thiopurine derivatives as well as biological drugs and biosimilars can be distinguished. Moreover, some novel biologics and small molecule drugs have shown potential in CD clinical trials, providing safe and effective results. This article provides an overview of the achievements in the field of biologic therapy, its efficacy and safety with an indication of future directions in CD treatment.


Assuntos
Terapia Biológica/métodos , Doença de Crohn/terapia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Doença de Crohn/etiologia , Humanos , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Inibidores do Fator de Necrose Tumoral/farmacologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico
16.
Eur J Nutr ; 59(6): 2481-2496, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31562532

RESUMO

PURPOSE: We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4). METHODS: Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies. RESULTS: COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO. CONCLUSION: Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.


Assuntos
Gorduras na Dieta/farmacologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Dor Visceral/dietoterapia , Animais , Óleo de Coco/química , Óleo de Coco/farmacologia , Diarreia/dietoterapia , Dietoterapia , Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores , Trânsito Gastrointestinal/efeitos dos fármacos , Ácidos Linoleicos/química , Ácidos Linoleicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oenothera biennis , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Ácido gama-Linolênico/química , Ácido gama-Linolênico/farmacologia
17.
Postepy Biochem ; 65(3): 224-230, 2019 10 01.
Artigo em Polonês | MEDLINE | ID: mdl-31643170

RESUMO

Berberine (BRB) is a compound belonging to the group of isoquinoline alkaloids of plant origin that has long been used in traditional chinese medicine (TMC). Due to, among others anti-inflammatory properties BRB is a potential therapeutic in the treatment of acute pancreatitis (OZT). In a study in the mouse model of L-arginine-induced acute pancreatitis, we showed that BRB administered by the intravenous route at 0.1 and 0.5 mg / kg body weight significantly reduces the level of myeloperoxidase activity (an indicator of inflammation) in the pancreas and lungs. Promising results point to the need for larger, randomized studies to assess the long-term efficacy and side effects of BRB therapy.


Assuntos
Berberina/uso terapêutico , Pancreatite/tratamento farmacológico , Doença Aguda/terapia , Animais , Berberina/farmacologia , Modelos Animais de Doenças , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia
18.
Pharmacol Rep ; 71(5): 899-908, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421543

RESUMO

BACKGROUND: Dietary interventions can improve gastrointestinal (GI) symptoms. We determined the effects of fatty acids (FAs) supplementation with medium- and long-chain saturated FAs on mouse GI motility and correlated them with the expression of genes for free FA receptors (FFAR)1-4, FA binding protein 4 (FABP4) and inflammation. METHODS: Forty-eight BalbC were assigned to: standard diet (STD), diet rich in medium-chain saturated FAs (COCO) and long-chain saturated FAs (HF) (7% by weight). Body weight (BW) and food intake (FI) were monitored for 8-weeks. GI motility was determined by fecal pellet output (FPO) and colon bead expulsion tests. FABP4 inhibitor, BMS309403 (1mg/kg, ip) was injected to half of each group 2 days/week. mRNA expression of FABP4, (FFAR)1-4, and pro-inflammatory cytokines were measured in colonic and splenic tissues using real-time PCR. RESULTS: COCO and HF decreased FI. COCO accelerated overall GI transit (p<0.05). COCO increased the mRNA expression of FFAR2 (p<0.001) and TNFα (p<0.01); HF increased the expression of FABP4 and FFAR4 (p<0.05), and FFAR2 (p<0.001) in the colon, and decreased FFAR1 and FFAR4 (p<0.001), TNFα (p<0.01) and IL-1ß (p<0.05) in splenic tissues. BMS309403 decreased the FI and delayed colonic transit in STD+BMS and COCO+BMS vs. STD (p<0.05). HF+BMS increased colonic expression of FFAR3 (p<0.01), TNFα (p<0.01), IL-6 (p<0.01), and reduced FFAR4 (p<0.05); COCO+BMS decreased TNFα (p<0.01). CONCLUSION: Diversification in the dietary lipid content affected GI motility in mice and the expression of FFARs and pro-inflammatory cytokines in vivo.


Assuntos
Colo/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Colo/imunologia , Colo/metabolismo , Citocinas/genética , Proteínas de Ligação a Ácido Graxo/genética , Metabolismo dos Lipídeos/genética , Masculino , Camundongos Endogâmicos BALB C , Receptores Acoplados a Proteínas G/genética , Baço/imunologia , Baço/metabolismo
19.
Pancreatology ; 19(4): 481-487, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079933

RESUMO

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can lead to local and systemic complications. Repeated attacks of AP can lead to chronic pancreatitis, which markedly increases the probability of developing pancreatic cancer. Although many researchers have attempted to identify the pathogenesis involved in the initiation and aggravation of AP, the disease is still not fully understood, and effective treatment is limited to supportive therapy. METHODS: We aim to summarize available literature focused on phytochemicals (berberine, chlorogenic acid, curcumin, emblica officinalis, ellagic acid, cinnamtannin B-1, resveratrol, piperine and lycopene) and discuss their effectiveness and therapeutic value for improving AP. RESULTS: This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. CONCLUSIONS: Many phytochemicals hold potential in improving AP symptoms and may be a valuable and effective addition to standard treatment of AP. It has already been proven that the crucial factor for reducing the severity of AP is stimulation of apoptosis along with/or inhibition of necrosis. Supplementation of phytochemicals, which target the balance between apoptosis and necrosis can be recommended in ongoing clinical studies.


Assuntos
Pancreatite/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Fitoterapia/métodos , Doença Aguda , Animais , Humanos , Resultado do Tratamento
20.
Neurogastroenterol Motil ; 31(9): e13651, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31145538

RESUMO

BACKGROUND: Food and diet are central issues for proper functioning of the cardiovascular (CV) system and gastrointestinal (GI) tract. We hypothesize that different types of dietary FAs affect CV parameters as well as GI motor function and visceral sensitivity. METHODS: Male Wistar rats were fed with control diet (CTRL), diet supplemented with 7% soybean oil (SOY), SOY + 3.5% virgin coconut oil (COCO), and SOY + 3.5% evening primrose oil (EP) for 4 weeks. The content of insoluble fiber in CTRL was higher than in SOY, COCO, or EP. Body weight gain and food/water intake were measured. At day 28, biometric, biochemical, CV parameters, GI motor function (X-ray and colon bead expulsion test), and visceral sensitivity were evaluated. Changes in propulsive colonic activity were determined in vitro. The colon and adipose tissue were histologically studied; the number of mast cells (MCs) in the colon was calculated. RESULTS: SOY, COCO, and EP had increased body weight gain but decreased food intake vs CTRL. Water consumption, biometric, biochemical, and CV parameters were comparable between groups. SOY increased the sensitivity to colonic distention. All groups maintained regular propulsive neurogenic contractions; EP delayed colonic motility (P < 0.01). SOY, COCO, and EP displayed decreased size of the cecum, lower number and size of fecal pellets, and higher infiltration of MCs to the colon (P < 0.001). CONCLUSIONS AND INFERENCES: Dietary FAs supplementation and lower intake of insoluble fiber can induce changes in the motility of the lower GI tract, in vivo and in vitro, but CV function and visceral sensitivity are not generally affected.


Assuntos
Pressão Sanguínea/fisiologia , Fibras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Motilidade Gastrointestinal/fisiologia , Frequência Cardíaca/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Óleo de Coco/administração & dosagem , Motilidade Gastrointestinal/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Óleo de Soja/administração & dosagem
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