RESUMO
BACKGROUND: Gelsectan® is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan® on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions. METHODS: Animals: Wistar rats received gavage with XOS, XG + PPGS or XG + PPGS + XOS, as a single dose or for 7 days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12 weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively. RESULTS: Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG + PPGS + XOS failed to reverse PRS, but 7 days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan® treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan® restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan® treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D. CONCLUSIONS: Gelsectan® prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan® can be considered as an effective therapy for IBS-D symptoms.
Assuntos
Diarreia , Modelos Animais de Doenças , Glucanos , Mucosa Intestinal , Síndrome do Intestino Irritável , Permeabilidade , Ratos Wistar , Xilanos , Animais , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/complicações , Diarreia/tratamento farmacológico , Diarreia/etiologia , Humanos , Ratos , Masculino , Xilanos/farmacologia , Xilanos/uso terapêutico , Xilanos/administração & dosagem , Feminino , Glucanos/farmacologia , Glucanos/administração & dosagem , Glucanos/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Adulto , Dor Visceral/tratamento farmacológico , Dor Visceral/etiologia , Reto/patologia , Pessoa de Meia-Idade , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacologia , Dor Abdominal/etiologia , Dor Abdominal/tratamento farmacológicoRESUMO
Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.
Assuntos
Hidrogéis , Receptor da Anafilatoxina C5a , Animais , Glucanos/farmacologia , Hidrogéis/farmacologia , Camundongos , Aderências Teciduais/prevenção & controle , Xilanos/farmacologia , Xilanos/uso terapêuticoRESUMO
The differences in the source and structure of xylans make them have various biological activities. However, due to their inherent structural limitations, the various biological activities of xylans are far lower than those of commercial drugs. Currently, several types of molecular modification methods have been developed to address these limitations, and many derivatives with specific biological activity have been obtained. Further research on structural characteristics, structure-activity relationship and mechanism of action is of great significance for the development of xylan derivatives. Therefore, the major molecular modification methods of xylans are introduced in this paper, and the primary structure and conformation characteristics of xylans and their derivatives are summarized. In addition, the biological activity and structure-activity relationship of the modified xylans are also discussed.
Assuntos
Xilanos/química , Xilanos/farmacologia , Bactérias/efeitos dos fármacos , Enzimas/química , Estrutura Molecular , Relação Estrutura-Atividade , Vírus/efeitos dos fármacos , Xilanos/uso terapêuticoRESUMO
Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy. This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2-3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC.
Assuntos
Oryza/química , Óleo de Farelo de Arroz/química , Cogumelos Shiitake/enzimologia , Xilanos/química , Enzimas/química , Humanos , Óleo de Farelo de Arroz/uso terapêutico , Xilanos/uso terapêuticoRESUMO
Alzheimer's disease (AD) is a debilitating and irreversible brain disease that affects an increasing number of aged individuals, mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent antioxidant, antiaging, and immunomodulatory effects. The aim of the present study was to investigate the protective effect of Biobran against sporadic Alzheimer's disease (SAD). SAD was induced in mice via intracerebroventricular injection of streptozotocin (STZ) (3 mg/kg). STZ-treated mice were administered with Biobran for 21 days. The effects of Biobran on memory and learning were measured via the Morris water maze, novel object recognition, and Y-maze tests. Biomarkers for apoptosis, oxidative stress, and amyloidogenesis were measured using ELISA and western blot analysis. Histopathological examination was performed to confirm neuronal damage and amyloid-beta deposition. Biobran reversed the spatial memory deficit in SAD-induced mice, and it increased the expression of glutathione, reduced malondialdehyde, decreased IL-6, decreased intercellular adhesion molecule-1 (ICAM-1), and significantly increased nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). Moreover, Biobran exerted a protective effect against amyloid-beta-induced apoptosis via the suppression of both cleaved caspase-3 and the proapoptotic protein Bax and via the upregulation of the antiapoptotic protein Bcl-2. Furthermore, it reduced the expression of forkhead box class O proteins. It could be concluded from this study that Biobran may be a useful nutritional antioxidant agent for protection against SAD through its activation of the gene expression of Nrf2/ARE, which in turn modulates the apoptotic and amyloidogenic pathways.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Apoptose , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Xilanos/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Animais , Elementos de Resposta Antioxidante/genética , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Caspase 3/metabolismo , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Glutationa/metabolismo , Inflamação/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Teste do Labirinto Aquático de Morris , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Teste de Campo Aberto , Estresse Oxidativo/efeitos dos fármacos , Placa Amiloide/patologia , Estreptozocina , Testes de Toxicidade Aguda , Xilanos/química , Xilanos/farmacologia , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Oral rehydration is the main treatment of acute diarrhea in children. This study was undertaken to evaluate the efficacy and safety of xyloglucan and gelose (agar-agar) plus oral rehydration solution (ORS) compared with placebo and ORS for reduction of acute diarrhea symptoms in children. METHODS: In a randomized, double-blind, placebo-controlled trial, children with acute gastroenteritis received xyloglucan/gelose plus ORS (n = 50) or placebo plus ORS (n = 50) for 5 days. Demographic, clinical, anthropometric and laboratory parameters were recorded and analyzed. RESULTS: Xyloglucan/gelose plus ORS reduced the total number of type 7 and 6 stools on the Bristol Stool Form scale (p = 0.040 and p = 0.015, respectively, compared to placebo plus ORS), and had a rapid onset of action, evident 6 hours post-treatment. Xyloglucan/gelose plus ORS also improved associated clinical symptoms (apathy, vomiting, flatulence, and blood in stool). compared with placebo plus ORS. Except for a generalized rash of unknown causality in a patient receiving placebo plus ORS, all other adverse events (dehydration, n = 7, cough, n = 1, exacerbation of vomiting, n = 1) were deemed unrelated to study medication. CONCLUSIONS: Xyloglucan/gelose plus ORS was effective and safe in treating acute diarrhea in children.
Assuntos
Ágar/uso terapêutico , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Gastroenterite/tratamento farmacológico , Glucanos/uso terapêutico , Soluções para Reidratação/uso terapêutico , Xilanos/uso terapêutico , Doença Aguda , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Hidratação/métodos , Gastroenterite/complicações , Humanos , Lactente , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Demand for safe, environmentally friendly and minimally processed food additives with intrinsic technological (stabilizing, texturizing, structuring) and functional potential is already on the rise. There are actually several natural excipients eligible for pharmaceutical formulation. Mucilage, as a class constitutes arabinoxylan and rhamnogalacturonan-based biomolecules used in the pharmaceutical, environmental as well as phytoremediation industries owing to its particular structure and properties. These compounds are widely used in pharmaceutical, food and cosmetics, as well as, in agriculture, paper industries. This review emphasizes mucilage valuable applications in the pharmaceutical and industrial fields. In this context, much focus has recently been given to the valorization of mucilage as an ingredient for food or nutraceutical applications. Furthermore, different optimization and extraction techniques are presented to develop better utilization and/or enhanced yield of mucilage. The highlighted mucilage extraction methods warrant assessing up-scale processes to encourage for its industrial applications. The current article capitalizes on cutting-edge characteristics of mucilage and posing for other possible innovative applications in non-food industries. Here, the first holistic overview of mucilage with regards to its physicochemical properties and potential novel usages is presented.
Assuntos
Biodegradação Ambiental , Mucilagem Vegetal/química , Polissacarídeos/química , Xilanos/química , Aditivos Alimentares/química , Aditivos Alimentares/uso terapêutico , Humanos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Mucilagem Vegetal/uso terapêutico , Polissacarídeos/uso terapêutico , Viscosidade , Xilanos/uso terapêuticoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, characterized by dryness and more or less severe itching. The etiology of AD is complex and has not been fully clarified, involving genetic susceptibility, immunological abnormalities, epidermal barrier dysfunction, and environmental factors. Xyloglucan (XG) and pea protein (PP) are two compounds of natural origin characterized by the ability to create a physical barrier that protects mucosae membranes, reducing inflammation. The aim of the present study was to evaluate the potential beneficial effects of XG + PP in both a mouse model of AD and Staphylococcus aureus (S.aureus) infection- associated AD. Mice were topically treated with 200 µL of 0.5% oxazolone on the dorsal skin three times a week for AD induction. Mice received XG and PP by topical administration 1 h before oxazolone treatment. In S. aureus infection-associated AD, to induce a superficial superinfection of the skin, mice were also treated with 5 µL of 108 of a culture of S. aureus for 2 weeks; mice superinfected received XG and PP by topical administration 1 h before oxazolone + S. aureus. Four weeks later, the skin was removed for histological and biochemical analysis. Our results demonstrated the protective barrier effects of XG and PP characterized by a reduction in histological tissue changes, mastocyte degranulation, and tight junction permeability in the skin following oxazolone treatment. Moreover, XG + PP was able to preserve filaggrin expression, a hallmark of AD. Our data also support the effectiveness of XG + PP to reduce the damage by superinfection post AD induced by S. aureus. In conclusion, a future product containing XG and PP could be considered as a potentially interesting approach for the treatment of AD.
Assuntos
Dermatite Atópica/tratamento farmacológico , Glucanos/uso terapêutico , Proteínas de Ervilha/uso terapêutico , Xilanos/uso terapêutico , Animais , Degranulação Celular/efeitos dos fármacos , Citocinas/metabolismo , Dermatite Atópica/complicações , Dermatite Atópica/patologia , Modelos Animais de Doenças , Eritema/complicações , Eritema/tratamento farmacológico , Eritema/patologia , Feminino , Proteínas Filagrinas , Glucanos/farmacologia , Inflamação/patologia , Proteínas de Filamentos Intermediários , Mastócitos/fisiologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Ocludina/metabolismo , Oxazolona/farmacologia , Proteínas de Ervilha/farmacologia , Pele/patologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Junções Íntimas/metabolismo , Xilanos/farmacologiaRESUMO
Butyrate has been shown to be effective in ulcerative colitis (UC). However, its oral administration is rare due to its rancid odour and unpleasant taste. In this study, the effect of a butyrate-releasing polysaccharide derivative, xylan butyrate ester (XylB), was evaluated in a dextran sodium sulphate (DSS)-induced UC model in C57BL/6 mice. Linear xylan was extracted from corn cobs. The C-2 and C-3 positions of the linear xylan were esterified with butyrate, forming XylB. The protective and therapeutic effects of XylB against UC were determined in a DSS-induced mouse model. The results showed that XylB treatments reversed the imbalance between pro- and anti-inflammatory cytokines. Moreover, XylB rebalanced the gut microbiota that interfered with DSS treatment and significantly decreased the relative abundance of the genera Oscillibacter, Ruminococcaceae UCG-009, Erysipelatoclostridium, and Defluviitaleaceae UCG-01. XylB increased butyrate content in the colon, upregulated G-protein coupled receptor 109A protein expression, inhibited histone deacetylase (HDAC) activity, and exerted anti-inflammatory activity through autophagy pathway activation and nuclear factor-κB (NF-κB) inhibition. XylB reduces inflammatory intestinal damage in mice, suggesting that it would be a potential drug for the treatment of UC and could be used to overcome the limitations of the oral administration of sodium butyrate.
Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Butiratos/metabolismo , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Xilanos/administração & dosagem , Xilanos/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Autofagia/efeitos dos fármacos , Sequência de Carboidratos , Colite/imunologia , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/imunologia , Colo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Xilanos/química , Xilanos/uso terapêuticoRESUMO
PURPOSE: The world's older population is growing rapidly and the need to find measures to combat age-associated decline of physical, mental, and cognitive functions and improve their health-related quality of life (HRQOL) is escalating. Biobran/MGN-3, an arabinoxylan rice bran, has been previously reported to improve the quality of life in cancer patients. The objective of the current study was to examine the effect of a low dose of Biobran/MGN-3 supplementation on the HRQOL in a healthy older adult population. METHODS: Sixty apparently healthy subjects, 40 males and 20 females, over 56 years old were recruited and blindly randomized into two group receiving either placebo or Biobran/MGN-3 (250 mg/day for 3 months). Participants did not take any vitamins or medications during the study and their health was closely monitored. HRQOL was assessed at the initiation and termination of the study using the previously validated Arabic version of SF-12v2 questionnaire. RESULTS: For all measured HRQOL domains, there was no statistically significant difference in baseline scores between the two groups. Compared to baseline values and placebo-treated subjects, Biobran/MGN-3 supplementation significantly enhanced the levels of physical and mental component summary scores as well as role-physical, bodily pain, vitality, and social functioning subdomain scores. CONCLUSION: These results show that Biobran/MGN-3 is a promising psychoneuroimmune modulatory agent that could improve the HRQOL in healthy old adults.
Assuntos
Qualidade de Vida , Xilanos , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oryza , Xilanos/uso terapêuticoRESUMO
Background: Irritable bowel syndrome (IBS) is highly prevalent and presents a clinical challenge. Gelsectan is a medical device containing xyloglucan (XG), pea protein and tannins (PPT) from grape seed extract, and xylo-oligosaccharides (XOS), which act together to protect and reinforce the intestinal barrier. Objective: The objective of this study is to evaluate the efficacy and safety of XG + PPT + XOS in patients with diarrhoea-predominant IBS (IBS-D). Methods: In this double-blind study, 60 patients were randomly assigned to receive XG + PPT + XOS or placebo for 28 days, then crossed over to the alternative treatment. Patients were followed for 60 days. Results: At Day 28, a significantly higher proportion of patients starting treatment with XG + PPT + XOS than placebo (87 vs 0%; p = 0.0019) presented normal stools (Bristol Stool Form Scale type 3-4). At Day 56, a significantly higher proportion of patients who crossed over to XG + PPT + XOS than placebo (93% vs 23%; p = 0.0001) presented normal stools. In the group allocated to receive XG + PPT + XOS after placebo, benefits of XG + PPT + XOS were maintained during follow-up. Subjective assessments of abdominal pain, bloating, quality of life and general health indicated significant improvement with XG + PPT + XOS over placebo. There were no related adverse events. Conclusion: XG + PPT + XOS effectively controlled diarrhoea and alleviated clinical symptoms in patients with IBS-D, and was well tolerated.
Assuntos
Demulcentes/uso terapêutico , Diarreia/tratamento farmacológico , Glucanos/uso terapêutico , Síndrome do Intestino Irritável/diagnóstico , Oligossacarídeos/uso terapêutico , Proteínas de Ervilha/uso terapêutico , Xilanos/uso terapêutico , Dor Abdominal/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adulto , Estudos Cross-Over , Demulcentes/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Desenho de Equipamento/instrumentação , Feminino , Seguimentos , Glucanos/administração & dosagem , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/psicologia , Masculino , Oligossacarídeos/administração & dosagem , Proteínas de Ervilha/administração & dosagem , Placebos/administração & dosagem , Prebióticos/administração & dosagem , Prevalência , Qualidade de Vida , Romênia/epidemiologia , Segurança , Resultado do Tratamento , Xilanos/administração & dosagemRESUMO
This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.
Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/radioterapia , Xilanos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Carcinoma de Ehrlich/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Feminino , Regulação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Fígado/efeitos da radiação , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiação , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Xilanos/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
In the last years, biomedical research has focused its efforts in the development of new oral delivery systems for the treatment of different diseases. Ferulated arabinoxylans are polysaccharides from cereals that have been gaining attention in the pharmaceutical field due to their prebiotic, antioxidant, and anticancer properties. The antioxidant and anticancer properties of these polysaccharides make them attractive compounds for the treatment of cancer, particularly colon cancer. In addition, ferulated arabinoxylans can form covalent gels through the cross-linking of their ferulic acids. Due to their particular characteristics, ferulated arabinoxylan gels represent an excellent alternative as colon-targeted drug delivery systems. The aim of the present work is to review the physicochemical and functional properties of ferulated arabinoxylans and their gels and to present the future perspectives for potential application as antioxidant and anticancer agents.
Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Géis/uso terapêutico , Xilanos/uso terapêutico , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Xilanos/farmacologiaRESUMO
Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a "mucin-like" molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders.
Assuntos
Glucanos/farmacologia , Mucosa/efeitos dos fármacos , Mucosa/metabolismo , Compostos Fitoquímicos/farmacologia , Polímeros/farmacologia , Substâncias Protetoras/farmacologia , Xilanos/farmacologia , Animais , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Suscetibilidade a Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Gastroenterite/tratamento farmacológico , Gastroenterite/etiologia , Gastroenterite/metabolismo , Gastroenterite/patologia , Glucanos/química , Glucanos/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Mucinas/metabolismo , Mucosa/citologia , Mucosa/imunologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia , Infecções Urinárias/metabolismo , Xilanos/química , Xilanos/uso terapêuticoRESUMO
BACKGROUND: Non-digestible carbohydrates present in cereals such as fructans and arabinoxylans represent promising prebiotic nutrients to prevent the development of obesity and related metabolic disorders. OBJECTIVE AND DESIGN: The aim of this study was to determine the corrective effects of wheat bran-derived arabinoxylan oligosaccharides in obese mice fed a western diet (WD). WD was given for 4 weeks before wheat bran extract (WBE) supplementation (5%) for an additional 4 weeks, whereas a control group received the standard diet. RESULTS: Bifidogenic effect of WBE was evidenced by an induction of both Bifidobacterium animalis and Bifidobacterium pseudolongum in the caecal content. WBE supplementation normalised WD-induced fat-mass expansion, steatosis, hypercholesterolemia, hyperleptinemia, hyperglycemia and hyperinsulinemia reaching the values of control mice. The reduced glucose-dependent insulinotropic polypeptide (GIP) release observed in WD + WBE mice may be a protective mechanism in terms of reducing adipose tissue storage, hepatic steatosis and glucose homoeostasis. CONCLUSION: We found that WBE completely abolished WD-induced metabolic disorders. Those results might be useful to take into account nutritional advices to treat obesity and related metabolic disorders such as type 2 diabetes, hypercholesterolaemia and fatty liver diseases when obesity was already established.
Assuntos
Bifidobacterium/efeitos dos fármacos , Dieta Ocidental/efeitos adversos , Doenças Metabólicas/tratamento farmacológico , Obesidade/tratamento farmacológico , Oligossacarídeos/uso terapêutico , Triticum/química , Xilanos/uso terapêutico , Tecido Adiposo/metabolismo , Animais , Bifidobacterium/crescimento & desenvolvimento , Glicemia/metabolismo , Ceco/microbiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Fibras na Dieta , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/microbiologia , Polipeptídeo Inibidor Gástrico/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/microbiologia , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/microbiologia , Hiperinsulinismo/sangue , Hiperinsulinismo/tratamento farmacológico , Hiperinsulinismo/microbiologia , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismo , Obesidade/microbiologia , Oligossacarídeos/farmacologia , Prebióticos , Xilanos/farmacologiaRESUMO
INTRODUCTION: The intestinal barrier controls the absorption of nutrients and water whilst helping to prevent the entry of toxins and pathogenic micro-organisms from the lumen into the tissues. Deficiencies in the barrier are associated with various gastrointestinal and extra digestive disorders. Areas covered: This review provides an overview of the relationship between increased intestinal permeability and disease, and considers the role of mucosal protectants (mucoprotectants) in restoring normal intestinal barrier function, with a particular focus on diarrheal disorders. Expert commentary: Impairment of the intestinal barrier characterizes a variety of diseases, and there is ongoing interest in the development of pharmacological approaches targeting the reduction of intestinal permeability. These include corticosteroids, aminosalicylates and anti-tumor necrosis factor-α (TNF-α), which act by reducing inflammation; probiotics, which modulate the production of mucin and epithelial tight junction proteins; and mucoprotectants, which form a protective film over the epithelium. Recently, preclinical and clinical data highlight, the ability of new mucoprotectants, such as gelatin tannate and xyloglucan, to protect the intestinal mucosa and to exert anti-diarrheal effects. In the future the ability of these substances to enhance the intestinal barrier may extend their use in the management of a variety of gastro-intestinal diseases associated with 'leaky gut'.
Assuntos
Demulcentes/uso terapêutico , Diarreia/tratamento farmacológico , Gelatina/uso terapêutico , Glucanos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Taninos/uso terapêutico , Xilanos/uso terapêutico , Demulcentes/efeitos adversos , Diarreia/diagnóstico , Diarreia/metabolismo , Diarreia/fisiopatologia , Gelatina/efeitos adversos , Glucanos/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Permeabilidade , Taninos/efeitos adversos , Resultado do Tratamento , Xilanos/efeitos adversosRESUMO
INTRODUCTION: Conventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies. OBJECTIVES: To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary therapy for conventional cancer treatment. METHODS: Systematic search of journal databases and gray literature for primary studies reporting the effects of MGN-3 on cancer and cancer treatment. RESULTS: Thirty full-text articles and 2 conference abstracts were included in this review. MGN-3 has been shown to possess immunomodulating anticancer effects and can work synergistically with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to act against carcinogenic agents, and inhibit tumor growth, either by itself or in combination with other anticancer compounds. Fourteen successful MGN-3 treated clinical cases were found. Eleven clinical studies, including 5 nonrandomized, pre-post intervention studies and 6 randomized controlled trials (RCTs) were located. Reported effects include enhanced immunoprofile, reduced side effects, improved treatment outcomes; one RCT established significantly increased survival rates. There are no reports on adverse events on MGN-3. Most of the clinical trials are small studies with short duration. CONCLUSION: There is sufficient evidence suggesting MGN-3 to be an effective immunomodulator that can complement conventional cancer treatment. However, more well-designed RCTs on MGN-3 are needed to strengthen the evidence base.
Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Xilanos/farmacologia , Xilanos/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Terapias Complementares/métodos , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Low intake of dietary fibre is associated with the development of type 2 diabetes. Dyslipidaemia plays a key role in the pathogenesis of type 2 diabetes. Knowledge of the impact of dietary fibres on postprandial lipaemia is, however, sparse. This study aimed in subjects with metabolic syndrome to assess the impact on postprandial lipaemia and features of the metabolic syndrome of a healthy carbohydrate diet (HCD) rich in cereal fibre, arabinoxylan and resistant starch compared to a refined-carbohydrate western-style diet (WSD). METHODS: Nineteen subjects completed the randomised, crossover study with HCD and WCD for 4-week. Postprandial metabolism was evaluated by a meal-challenge test and insulin sensitivity was assessed by HOMA-IR and Matsuda index. Furthermore, fasting cholesterols, serum-fructosamine, circulating inflammatory markers, ambulatory blood pressure and intrahepatic lipid content were measured. RESULTS: We found no diet effects on postprandial lipaemia. However, there was a significant diet × statin interaction on total cholesterol (P = 0.02) and LDL cholesterol (P = 0.002). HCD decreased total cholesterol (-0.72 mmol/l, 95% CI (-1.29; -0.14) P = 0.03) and LDL cholesterol (-0.61 mmol/l, 95% CI (-0.86; -0.36) P = 0.002) compared with WSD in subjects on but not without statin treatment. We detected no other significant diet effects. CONCLUSIONS: In subjects with metabolic syndrome on statins a 4-week diet rich in arabinoxylan and resistant starch improved fasting LDL and total cholesterol compared to subjects not being on statins. However, we observed no diet related impact on postprandial lipaemia or features of the metabolic syndrome. The dietary fibre x statin interaction deserves further elucidation.
Assuntos
Fibras na Dieta/uso terapêutico , Dislipidemias/tratamento farmacológico , Resistência à Insulina , Síndrome Metabólica/dietoterapia , Amido/uso terapêutico , Grãos Integrais , Xilanos/uso terapêutico , Adulto , Idoso , Biomarcadores , Estudos Cross-Over , Dieta Ocidental/efeitos adversos , Fibras na Dieta/metabolismo , Digestão , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Feminino , Manipulação de Alimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediadores da Inflamação/sangue , Masculino , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Modelos Estatísticos , Período Pós-Prandial , Amido/metabolismo , Xilanos/metabolismoRESUMO
The objective of this study was to determine the impact of wheat bran and its main polysaccharides on intestinal bacteria and gene expression of intestinal barrier function relevant proteins. Thirty freshly weaned male piglets were assigned randomly to five dietary treatment groups with six piglets per group. Accordingly, five synthetic diets including a basal control diet without fiber components (CON), wheat bran diet (10% wheat bran, WB), arabinoxylan diet (AX), cellulose diet (CEL) and combined diet of arabinoxylan and cellulose (CB) were studied. The piglets were fed ad libitum for 30 d. Lower Escherichia coli (E. coli) populations in WB group and higher probiotic (Lactobacillus and Bifidobacterium) populations in groups fed diets containing arabinoxylan (WB, AX and CB) were observed and compared with CON group. Compared with CON group, the gene expressions of cystic fibrosis transmembrane conductance regulator (CFTR), calcium-activated chloride channel regulator 1 (CLCA1) and voltage-gated chloride channel 2 (CIC2) were suppressed in the WB group. And wheat bran down-regulated gene expression of pro-inflammation (TNF-α, IL-1ß, IL-6) and TLRs/MyD88/NF-κB pathway compared with CON group. In conclusion, wheat bran and its main polysaccharides could change intestinal microflora and down-regulate the gene expression of intestinal barrier function relevant proteins in the distal small intestinal mucosa.