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1.
Int J Biol Macromol ; 276(Pt 1): 133840, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39004250

RESUMEN

We previously found that modified citrus pectin (MCP), an inhibitor of pro-inflammatory factor Galectin-3 (Gal-3), has significant anti-inflammatory and chondroprotective effects. In this study, a hyaluronate (HA) gel-based sustained release system of MCP (MCP-HA) was developed as an anti-inflammatory agent for chronic inflammation for osteoarthritis (OA) treatment. The MCP-HA gel was injected into the knee joint cavities of OA rabbit models induced by anterior cruciate ligament transection (ACLT) or modified Hulth method once a week for five weeks. We found that MCP-HA could improve the symptoms and signs of OA, protect articular cartilage from degeneration, suppress synovial inflammation, and therefore alleviate OA progression. Proteomic analysis of the synovial fluid obtained from the knee joints of OA rabbits revealed that MCP-HA synergistically regulated the levels of multiple inflammatory mediators and proteins involved in metabolic pathways. Taken together, our results demonstrate that the MCP-HA shows a synergistic effect of HA and MCP by modulating both inflammation and metabolic processes, thereby alleviating OA progression. The MCP-HA sustained release system has promising potential for long-term use in OA treatment.


Asunto(s)
Ácido Hialurónico , Osteoartritis , Pectinas , Pectinas/farmacología , Pectinas/química , Pectinas/administración & dosificación , Animales , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Conejos , Inyecciones Intraarticulares , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Geles , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Masculino , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Cartílago Articular/metabolismo , Líquido Sinovial/metabolismo , Líquido Sinovial/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación
2.
J Equine Vet Sci ; 139: 105128, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38852926

RESUMEN

Surgical site infection (SSI) is a common complication after celiotomy in horses, leading to increased morbidity and costs. Increased concern about antibiotic resistance justifies evaluation of alternative preventive approaches, such a Manuka honey which has displayed antimicrobial properties. Pectin-Honey Hydrogels (PHH), composed by Manuka honey and pectin provide a moist wound environment and microbial growth inhibition. The aim of the study was to evaluate the effectiveness of PHHs in preventing SSI in horses subjected to emergency laparotomy. Horses undergoing laparotomy were evaluated. Horses were randomly divided into two groups: Group 1 received PHH application onto the sutured linea alba before skin closure, while Group 2 received no treatment. Horses with postoperative antimicrobial administration or survival of less than 5 days were excluded. The incidence of SSIs was reported as percentages and compared between groups. Out of 44 horses enrolled in the study, only thirty-six were ultimately included. Exclusions occurred either due to death before 5 days postoperatively (2 horses) or the administration of postoperative antimicrobials (6 horses). The median length of hospitalization was 9 days (range 8-14 days). The overall occurrence of SSI was 19.4 %. One out of eighteen horses (5.5 %) in Group 1 and 6 out of 18 (33.3 %) horses in Group 2 developed SSI. Group 2 had an 8.5-fold increased risk of SSI (p = 0.035, OR = 8.5, 95 % CI. 0.9-80.07). No macroscopically visible adverse reactions were associated with PHH. PHH placed at the abdominal incision during surgery was safe and reduced the prevalence of SSI in horses.


Asunto(s)
Miel , Enfermedades de los Caballos , Hidrogeles , Laparotomía , Pectinas , Infección de la Herida Quirúrgica , Animales , Caballos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/veterinaria , Infección de la Herida Quirúrgica/epidemiología , Proyectos Piloto , Laparotomía/efectos adversos , Laparotomía/veterinaria , Enfermedades de los Caballos/prevención & control , Enfermedades de los Caballos/cirugía , Hidrogeles/administración & dosificación , Pectinas/administración & dosificación , Masculino , Femenino
3.
Int J Pharm ; 661: 124386, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38942182

RESUMEN

Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the Tmax (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent anti-adhesion properties and could be developed as a drug delivery system.


Asunto(s)
Sistemas de Liberación de Medicamentos , Emulsiones , Fluorouracilo , Geles , Pectinas , Polisacáridos Bacterianos , Animales , Fluorouracilo/administración & dosificación , Fluorouracilo/química , Polisacáridos Bacterianos/química , Adherencias Tisulares/prevención & control , Masculino , Pectinas/química , Pectinas/administración & dosificación , Liberación de Fármacos , Complicaciones Posoperatorias/prevención & control , Ratones , Humanos , Ratas Sprague-Dawley , Ratas , Preparaciones de Acción Retardada , Polisacáridos/química , Polisacáridos/administración & dosificación
4.
Drug Deliv Transl Res ; 14(10): 1-17, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38789909

RESUMEN

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.


Asunto(s)
Disponibilidad Biológica , Colon , Emulsiones , Flavonoides , Flavonoles , Galactanos , Pectinas , Polisacáridos Bacterianos , Flavonoles/farmacocinética , Flavonoles/administración & dosificación , Flavonoles/química , Animales , Colon/metabolismo , Flavonoides/farmacocinética , Flavonoides/administración & dosificación , Flavonoides/química , Masculino , Administración Oral , Galactanos/química , Galactanos/farmacocinética , Galactanos/administración & dosificación , Pectinas/química , Pectinas/farmacocinética , Pectinas/administración & dosificación , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/farmacocinética , Polisacáridos Bacterianos/administración & dosificación , Gomas de Plantas/química , Gomas de Plantas/farmacocinética , Gomas de Plantas/administración & dosificación , Mananos/química , Mananos/farmacocinética , Mananos/administración & dosificación , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Nanopartículas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Liberación de Fármacos , Solubilidad
5.
J Nutr ; 154(7): 2014-2028, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735572

RESUMEN

BACKGROUND: The gut microbiota contributes to metabolic disease, and diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via gut microbiota alterations. Fiber intake is linked with improvements in metabolic homeostasis in rodents and humans, which is associated with changes in the gut microbiota. However, dietary fiber is extremely heterogeneous, and it is imperative to comprehensively analyze the impact of various plant-based fibers on metabolic homeostasis in an identical setting and compare the impact of alterations in the gut microbiota and bacterially derived metabolites from different fiber sources. OBJECTIVES: The objective of this study was to analyze the impact of different plant-based fibers (pectin, ß-glucan, wheat dextrin, resistant starch, and cellulose as a control) on metabolic homeostasis through alterations in the gut microbiota and its metabolites in high-fat diet (HFD)-fed mice. METHODS: HFD-fed mice were supplemented with 5 different fiber types (pectin, ß-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (wt/wt) for 18 wk (n = 12/group), measuring body weight, adiposity, indirect calorimetry, glucose tolerance, and the gut microbiota and metabolites. RESULTS: Only ß-glucan supplementation during HFD-feeding decreased adiposity and body weight gain and improved glucose tolerance compared with HFD-cellulose, whereas all other fibers had no effect. This was associated with increased energy expenditure and locomotor activity in mice compared with HFD-cellulose. All fibers supplemented into an HFD uniquely shifted the intestinal microbiota and cecal short-chain fatty acids; however, only ß-glucan supplementation increased cecal butyrate concentrations. Lastly, all fibers altered the small-intestinal microbiota and portal bile acid composition. CONCLUSIONS: These findings demonstrate that ß-glucan consumption is a promising dietary strategy for metabolic disease, possibly via increased energy expenditure through alterations in the gut microbiota and bacterial metabolites in mice.


Asunto(s)
Dieta Alta en Grasa , Fibras de la Dieta , Microbioma Gastrointestinal , Homeostasis , Ratones Endogámicos C57BL , Animales , Fibras de la Dieta/farmacología , Fibras de la Dieta/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , beta-Glucanos/farmacología , beta-Glucanos/administración & dosificación , Pectinas/farmacología , Pectinas/administración & dosificación
6.
Biomater Sci ; 12(12): 3212-3228, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38757193

RESUMEN

Oral administration, while convenient, but complex often faces challenges due to the complexity of the digestive environment. In this study, we developed a nanoliposome (NLP) encapsulating psoralen (P) and coated it with chitosan (CH) and pectin (PT) to formulate PT/CH-P-NLPs. PT/CH-P-NLPs exhibit good biocompatibility, superior to liposomes loaded with psoralen and free psoralen alone. After oral administration, PT/CH-P-NLPs remain stable in the stomach and small intestine, followed by a burst release of psoralen after reaching the slightly alkaline and gut microbiota-rich colon segment. In the DSS-induced ulcerative colitis of mice, PT/CH-P-NLPs showed significant effects on reducing inflammation, mitigating oxidative stress, protecting the integrity of the colon mucosal barrier, and modulating the gut microbiota. In conclusion, the designed nanoliposomes demonstrated the effective application of psoralen in treating ulcerative colitis.


Asunto(s)
Colitis Ulcerosa , Colon , Sulfato de Dextran , Ficusina , Liposomas , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Animales , Liposomas/química , Ficusina/química , Ficusina/administración & dosificación , Ficusina/farmacología , Ratones , Administración Oral , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Sulfato de Dextran/química , Sulfato de Dextran/administración & dosificación , Nanopartículas/química , Nanopartículas/administración & dosificación , Pectinas/química , Pectinas/administración & dosificación , Pectinas/farmacología , Ratones Endogámicos C57BL , Masculino , Quitosano/química , Quitosano/administración & dosificación
7.
Biomed Pharmacother ; 174: 116561, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38593705

RESUMEN

Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.


Asunto(s)
Suplementos Dietéticos , Microbioma Gastrointestinal , Voluntarios Sanos , Pectinas , Humanos , Pectinas/administración & dosificación , Pectinas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Adulto , Método Doble Ciego , Femenino , Adulto Joven , Rhinovirus/efectos de los fármacos , Persona de Mediana Edad , Heces/microbiología , Bifidobacterium/efectos de los fármacos
8.
Drug Deliv Transl Res ; 14(9): 2461-2473, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38296909

RESUMEN

Artemisia argyi, commonly known as wormwood, is a traditional Chinese herbal food and medicine celebrated for its notable antibacterial and anti-inflammatory properties. This study explores a novel delivery method for wormwood, aiming for more convenient and versatile applications. Specifically, we present the first investigation into combining wormwood with microstructures to create a microneedle (MN) patch for wound healing. The wormwood microneedle (WMN) patch is formulated with milled wormwood sap, calcium carbonate, and sodium hyaluronate. The addition of 0.3% (w/v) sodium hyaluronate enhances the mechanical strength of the WMN patch. Pectin, derived from wormwood, is combined with calcium carbonate to create a gelatinous and solidified substance. The WMN patch exhibits a well-defined shape and sufficient mechanical strength to penetrate the epidermis, as confirmed by our results. In vitro experiments demonstrate the biocompatibility of the WMN patch with fibroblasts and highlight its antibacterial and anti-inflammatory properties. Furthermore, the patch facilitates collagen deposition at the wound site. In an excisional rat model, the WMN patch significantly accelerates the wound closure rate compared to the control group. Our findings suggest that the WMN patch has the potential to serve as a natural treatment for wound healing. Additionally, this approach can be extended to other biologically active substances with similar physiochemical characteristics in future applications.


Asunto(s)
Artemisia , Agujas , Ratas Sprague-Dawley , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Artemisia/química , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/química , Ácido Hialurónico/química , Ácido Hialurónico/administración & dosificación , Ratas , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Fibroblastos/efectos de los fármacos , Pectinas/química , Pectinas/administración & dosificación , Ratones , Humanos
9.
Fish Physiol Biochem ; 47(6): 2015-2025, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34709495

RESUMEN

To reveal the impact of dietary fiber (DF) on the bile acid (BA) profiles of fish, yellow catfish (Pelteobagrus fulvidraco) were fed a diet containing 300 g kg-1 dextrin (CON diet, control) or pectin (a type of soluble DF, PEC diet) for 7 days, and then the BA profiles were analyzed by UHPLC-MS/MS. A total of 26 individuals of BAs were detected in the fish body, with 8, 10, 14, and 22 individuals of BAs detected in the liver, serum, bile, and hindgut digesta, respectively. The conjugated BAs (CBAs) of fish were dominated by taurine CBAs (TCBAs). The concentrations of free BAs (FBAs) and the value of FBAs/CBAs in the bile of fish fed the PEC diet were nearly 5 and 7 times higher, respectively than those in fish fed the CON diet. The value of glycine CBAs/TCBAs in the liver, serum and bile of fish fed the PEC diet was significantly lower, and in the hindgut digesta was higher than that of fish fed the CON diet (P < 0.05). These results suggested that dietary pectin greatly changed the BA profiles of Pelteobagrus fulvidraco, attributed to inhibition of reabsorption of BAs. Therefore, attention should be paid to the impact on BA homeostasis when replacing fishmeal with DF-rich plant ingredients in the fish diet.


Asunto(s)
Ácidos y Sales Biliares , Bagres , Pectinas/administración & dosificación , Animales , Ácidos y Sales Biliares/análisis , Dieta/veterinaria , Hígado , Espectrometría de Masas en Tándem , Taurina
10.
Carbohydr Polym ; 270: 118377, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34364621

RESUMEN

Several studies are described that contribute to the systematic exploration of new aspects of digestion, fermentation, and biological activities of pectic polysaccharides (PPS) leading to a better understanding of prebiotics. Inflammatory bowel disease (IBD) is thought to be associated with the dysbacteriosis induced by different environmental agents in genetically susceptible persons. PPS are considered as an indispensable gut-microbiota-accessible carbohydrate that play a dominant role in maintaining gut microbiota balance and show a better effect in ameliorating IBD than some traditional prebiotics. The aim of this review is to summarize the fermentation characteristics of PPS, highlight its role in improving IBD, and propose a view that PPS may be a new and effective prebiotic.


Asunto(s)
Colitis/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Pectinas/administración & dosificación , Polisacáridos/administración & dosificación , Prebióticos/administración & dosificación , Animales , Línea Celular , Colitis/metabolismo , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/metabolismo , Digestión/efectos de los fármacos , Disbiosis/tratamiento farmacológico , Femenino , Fermentación , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Masculino , Ratones , Pectinas/metabolismo , Polisacáridos/metabolismo , Ratas
11.
Carbohydr Polym ; 270: 118383, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34364625

RESUMEN

The elucidation of the oral absorption of natural polysaccharides contributes to their further research and utilization. Herein, to explore the absorption of a pectin-type polysaccharide from Smilax china L. (SCLP), SCLP was respectively fluorescently labeled with fluorescein-5-thioicarbazide (FSCLP) and Cyanine7 amine (Cy7-SCLP) for in vitro and in vivo tracking. The near-infrared imaging demonstrated that Cy7-SCLP was absorbable in the small intestine and distributed in the liver and kidney after oral administration. Subsequently, in vitro intestinal epithelial tissue experiments showed that the jejunum was the dominant site of FSCLP transport. Further transport studies in the Caco-2 cell monolayer illustrated that FSCLP was delivered across the monolayer via transcellular transport by caveolae-mediated endocytosis and macropinocytosis together with paracellular transport by reversibly affecting tight junctions. In summary, this work presents the oral absorption characteristics and mechanisms of SCLP through the intestinal epithelium, which will facilitate the further development of SCLP and pectin polysaccharides.


Asunto(s)
Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Pectinas/farmacocinética , Polisacáridos/farmacocinética , Smilax/química , Administración Oral , Animales , Células CACO-2 , Endocitosis , Fluoresceína/administración & dosificación , Humanos , Mucosa Intestinal/efectos de los fármacos , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Pectinas/administración & dosificación , Polisacáridos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Uniones Estrechas , Transcitosis
12.
Mol Nutr Food Res ; 65(18): e2100222, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34268870

RESUMEN

SCOPE: Intestinal mucositis is a common side effect of the chemotherapeutic agent doxorubicin, which is characterized by severe Toll-like receptor (TLR) 2-mediated inflammation. The dietary fiber pectin is shown to prevent this intestinal inflammation through direct inhibition of TLR2 in a microbiota-independent manner. Recent in vitro studies show that inhibition of TLR2 is determined by the number and distribution of methyl-esters of pectins. Therefore, it is hypothesized that the degree of methyl-esterification (DM) and the degree of blockiness (DB) of pectins determine attenuating efficacy on doxorubicin-induced intestinal mucositis. METHODS AND RESULTS: Four structurally different pectins that differed in DM and DB are tested on inhibitory effects on murine TLR2 in vitro, and on doxorubicin-induced intestinal mucositis in mice. These data demonstrate that low DM pectins or intermediate DM pectins with high DB have the strongest inhibitory impact on murine TLR2-1 and the strongest attenuating effect on TLR2-induced apoptosis and peritonitis. Intermediate DM pectin with a low DB is, however, also effective in preventing the induction of doxorubicin-induced intestinal damage. CONCLUSION: These pectin structures with stronger TLR2-inhibiting properties may prevent the development of doxorubicin-induced intestinal damage in patients undergoing chemotherapeutic treatment with doxorubicin.


Asunto(s)
Doxorrubicina/efectos adversos , Intestino Delgado/efectos de los fármacos , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Pectinas/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antibióticos Antineoplásicos/efectos adversos , Apoptosis/efectos de los fármacos , Línea Celular , Relación Dosis-Respuesta a Droga , Esterificación , Femenino , Enfermedades Intestinales/inducido químicamente , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/patología , Mucosa Intestinal/efectos de los fármacos , Intestino Delgado/patología , Ratones Endogámicos C57BL , Mucositis/patología , Pectinas/administración & dosificación , Pectinas/química , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Peritonitis/patología , Relación Estructura-Actividad , Receptor Toll-Like 2/antagonistas & inhibidores , Receptor Toll-Like 2/metabolismo
13.
Front Endocrinol (Lausanne) ; 12: 676869, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34168616

RESUMEN

Diet-induced gastrointestinal distension is known to evoke satiation and suppress postprandial hyperglycemia; however, the underlying mechanisms remain poorly understood. This study explored how gastrointestinal distension regulates energy homeostasis by using inflating stomach formulation (ISF), the carbonated solution containing pectin that forms stable gel bubbles under acidic condition in the stomach. Here we show that, in mice, oral administration of ISF induced distension of stomach and proximal intestine temporarily, stimulated intestinal glucagon-like peptide-1 (GLP-1) secretion, and activated vagal afferents and brainstem. ISF suppressed food intake and improved glucose tolerance via enhancing insulin sensitivity. The anorexigenic effect was partially inhibited, and the beneficial glycemic effect was blunted by pharmacological GLP-1 receptor blockade and chemical denervation of capsaicin-sensitive sensory nerves. In HFD-fed obese mice showing arrhythmic feeding and obesity, subchronic ISF treatment at the light period (LP) onset for 10 days attenuated LP hyperphagia and visceral fat accumulation. These results demonstrate that gastrointestinal distension by ISF stimulates GLP-1 secretion and the vagal afferent signaling to the brain, thereby regulating feeding behavior and glucose tolerance. Furthermore, subchronic ISF treatment ameliorates HFD-induced visceral obesity. We propose the diet that induces gastrointestinal distension as a novel treatment of hyperphagic obesity and diabetes.


Asunto(s)
Bebidas Gaseosas , Ingestión de Alimentos/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Insulina/sangre , Intestinos/efectos de los fármacos , Pectinas/administración & dosificación , Nervio Vago/efectos de los fármacos , Animales , Dieta Alta en Grasa , Conducta Alimentaria/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Ratones , Saciedad/efectos de los fármacos
14.
Theranostics ; 11(9): 4155-4170, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33754054

RESUMEN

Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8+ T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Microbioma Gastrointestinal/fisiología , Pectinas/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano , Animales , Bacterias , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/metabolismo , Microambiente Tumoral/efectos de los fármacos
15.
Expert Rev Clin Pharmacol ; 14(4): 457-464, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33612037

RESUMEN

INTRODUCTION: Galectin-3 (Gal-3) is a ß-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients. AREAS COVERED: This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials. EXPERT OPINION: Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.


Asunto(s)
Proteínas Sanguíneas/antagonistas & inhibidores , Galectinas/antagonistas & inhibidores , Cirrosis Hepática/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Pectinas/administración & dosificación , Pectinas/farmacología , Índice de Severidad de la Enfermedad
16.
Int J Biol Macromol ; 171: 308-319, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33421467

RESUMEN

Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p < 0.05) higher than the control after 21-day treatment and wound closure was ~99% without any adverse systemic reactions. Histological analysis qualitatively revealed an enhanced re-epithelialization and collagen deposition. Moreover, results also showed an improved rate of collagen synthesis and angiogenesis in the group treated with the hydrogel film loaded with Simvastatin. Thus, the present study demonstrated that developed film holds great potential for the acceleration of diabetic wound healing by its pro-angiogenic effect, faster re-epithelialization and increased collagen deposition.


Asunto(s)
Alginatos/administración & dosificación , Apósitos Biológicos , Diabetes Mellitus Experimental/complicaciones , Hidrogeles , Pectinas/administración & dosificación , Simvastatina/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Alginatos/química , Animales , Colágeno/biosíntesis , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Hidrogeles/administración & dosificación , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Hidroxiprolina/análisis , Masculino , Ensayo de Materiales , Neovascularización Fisiológica/efectos de los fármacos , Pectinas/química , Distribución Aleatoria , Ratas , Ratas Wistar , Repitelización/efectos de los fármacos , Simvastatina/farmacología , Simvastatina/uso terapéutico , Piel/lesiones , Factor A de Crecimiento Endotelial Vascular/biosíntesis
17.
Int J Biol Macromol ; 171: 275-287, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33422511

RESUMEN

In this work, cashew apple pectin (CP) of the species Anacardium occidentale L. was used as an encapsulation matrix for hydrophobic drugs. The model drug chosen was mangiferin (Mf), a glycosylated C-xanthone which has antioxidant properties but low solubility in aqueous medium. CP (1-100 µg mL-1) was not toxic to human neutrophils and also did not significantly interfere with the pro-inflammatory mechanism of these cells in the concentration range of 12.5 and 100 µg mL-1. The results are promising because they show that pectin encapsulated mangiferin after spray drying presented an efficiency of 82.02%. The results obtained in the dissolution test, simulating the release of mangiferin in the gastrointestinal tract (pH 1.2, 4.6 and 6.8) and using Franz diffusion cells (pH 7.4), showed that cashew pectin may be a promising vehicle in prolonged drug delivery systems for both oral and dermal applications.


Asunto(s)
Anacardium/química , Portadores de Fármacos/administración & dosificación , Composición de Medicamentos/métodos , Neutrófilos/efectos de los fármacos , Pectinas/administración & dosificación , Secado por Pulverización , Xantonas/administración & dosificación , Cápsulas , Degranulación de la Célula/efectos de los fármacos , Células Cultivadas , Técnicas de Química Analítica , Preparaciones de Acción Retardada , Difusión , Liberación de Fármacos , Frutas/química , Humanos , Microscopía Electrónica de Rastreo , Pectinas/aislamiento & purificación , Peroxidasa/análisis , Solubilidad , Viscosidad
18.
J Sci Food Agric ; 101(3): 863-870, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33433910

RESUMEN

BACKGROUND: Protecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated. RESULTS: OP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, the upregulation of AP-related proteins including ZO-1, occludin, the antibacterial peptide-defensin-1 (DEFB1) and cathelicidin-related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP-induced intestinal inflammation. For the above, the effect of OP was better than COP. CONCLUSION: Dietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry.


Asunto(s)
Abelmoschus/química , Ceruletida/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Pectinas/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Citocinas/genética , Citocinas/inmunología , Frutas/química , Humanos , Mucosa Intestinal/inmunología , Masculino , Ratones , Ocludina/genética , Ocludina/inmunología , Pancreatitis/inducido químicamente , Pancreatitis/genética , Pancreatitis/inmunología , Pectinas/química , Extractos Vegetales/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/inmunología
19.
Fish Shellfish Immunol ; 107(Pt A): 357-366, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33132175

RESUMEN

The disposal of cacao pod husk, a byproduct of cacao bean processing, can cause serious adverse environmental impacts, motivating scientist to explore and develop potential beneficial applications of this resource. Dried cacao pod husk was extracted with ethanol to obtain a 10.6% pectin of cacao pod husks (pCPH), and its effects on the immunocompetence of Litopenaeus vannamei were estimated. Measured variables included total haemocyte count, differential haemocyte count, phenoloxidase activity, respiratory bursts, as well as phagocytic activity and clearance efficiency against Vibrio alginolyticus after receiving pCPH at 0, 1.5, 3, and 6 µg shrimp-1 for 0, 1, 3 and 7 days via injection, and their resistance to thermal stress and V. alginolyticus infection were further evaluated. No significant differences were observed in total haemocyte count, differential haemocyte count, and respiratory bursts in shrimp receiving pCPH at 1.5 µg shrimp-1 for 1 day; however, these variables were significantly elevated after 3 days of injection, compared to the control group. The significantly increased phenoloxidase activity was assessed in shrimp receiving pCPH at 1.5, 3 and 6 µg shrimp-1 within 3 days, and activity returned to the baseline after 7 days. Furthermore, the reduced phenoloxidase activity per granulocytes or respiratory bursts per haemocytes maintained homeostasis following the variation of haemogram. For gene expression assessments in haemocytes, the immune-related genes of the lipopolysaccharide and ß-1,3-glucan binding protein, prophenoloxidase II and anti-lipopolysaccharide factor as well as innate immune signaling pathway-related genes of toll-like receptors 1 and 3 significantly increased after shrimp received pCPH for 1 day. The increases in phagocytic activity and clearance efficiency were only detected in shrimp receiving pCPH at 6 µg shrimp-1 within 7 days, compared to the control. There was no significant difference in the mortality ratio of shrimp against hyperthermal stress when they received pCPH for 1 day, and the significant higher resistance to hypothermal stress and V. alginolyticus infection were found in shrimp received pCPH at 6 µg shrimp-1 for 1 days than those in the other treatments. It is therefore found that pCPH triggers immune responses serving as an immunostimulant capable of enhancing resistance against V. alginolyticus and hypothermal stress.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Cacao/química , Pectinas/farmacología , Penaeidae/inmunología , Vibrio alginolyticus/fisiología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Nueces/química , Pectinas/administración & dosificación , Vibrio alginolyticus/efectos de los fármacos
20.
J Trauma Acute Care Surg ; 89(5): 915-919, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33108138

RESUMEN

BACKGROUND: Persistent air leaks after thoracic trauma are associated with significant morbidity. To evaluate a novel pectin sealant in a swine model of traumatic air leaks, we compared a pectin biopolymer with standard surgical and fibrin-based interventions. METHODS: A standardized lung injury was created in male Yorkshire swine. Interventions were randomized to stapled wedge resection (n = 5), topical fibrin glue (n = 5), fibrin patch (n = 5), and a pectin sealant (n = 6). Baseline, preintervention and postintervention tidal volumes (TV) were recorded. Early success was defined as the return to near-normal TV (>95% of baseline). Late success was defined as no detectable air leak in the chest tube after chest closure. RESULTS: There were no differences in injury severity between groups (mean TV loss, 62 ± 17 mL, p = 0.2). Early success was appreciated in 100% (n = 6) of the pectin interventions which was significantly better than the fibrin sealant (20%, n = 1), fibrin patch (20%, n = 1), and stapled groups (80%, n = 4, p = 0.01). The percent of return to baseline TV after sealant intervention was significantly increased in the pectin (98%) and staple arms (97%) compared with the fibrin sealant (91%) and fibrin patch arms (90%) (p = 0.02; p = 0.03). Late success was also improved with the pectin sealant: no air leak was detected in 83% of the pectin group compared with 40% in the stapled group (p = 0.008)-90% of the fibrin-based interventions resulted in continuous air leaks (p = 0.001). CONCLUSION: Pectin-based bioadhesives effectively seal traumatic air leaks upon application in a porcine model. Further testing is warranted as they may provide a superior parenchymal-sparing treatment option for traumatic air leaks.


Asunto(s)
Lesión Pulmonar Aguda/terapia , Lesión Pulmonar/terapia , Pectinas/administración & dosificación , Adhesivos Tisulares/administración & dosificación , Animales , Modelos Animales de Enfermedad , Adhesivo de Tejido de Fibrina/administración & dosificación , Humanos , Masculino , Neumonectomía , Grapado Quirúrgico , Sus scrofa
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