ABSTRACT
This study is to investigate the protective effects of Eurotium cristatum intracellular polysaccharides (ECIP) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). The oral administration of ECIP could downregulate the disease activity index (DAI) and ameliorate the colonic shortening, immune stress, and damage caused by DSS. In addition, ECIP treatment increased the colonic contents of SCFAs including acetic, propionic, and butyric acids in UC mice. Targeted and untargeted metabolic analysis suggested that ECIP dramatically altered the tryptophan metabolism in the feces of UC mice and promoted the conversion of tryptophan into indole metabolites including indolepyruvate and indole-3-acetic acid (IAA) and indolealdehyde (IAId). Moreover, ECIP observably increased the content of colonic IL-22 and stimulated the relative concentration and relative expression of tight junction molecules in mRNA and proteins levels. Conclusively, consumption of ECIP can improve colon damage and its related effects of UC by promoting the production of IAA and IAId to reinforce intestinal barriers.
Subject(s)
Colitis, Ulcerative , Colon , Mice, Inbred C57BL , Polysaccharides , Tryptophan , Animals , Mice , Tryptophan/metabolism , Male , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/drug therapy , Humans , Colon/metabolism , Colon/drug effects , Polysaccharides/pharmacology , Polysaccharides/metabolism , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Dextran Sulfate/adverse effects , Indoleacetic Acids/metabolism , Interleukin-22 , Gastrointestinal Microbiome/drug effectsABSTRACT
Rats can condition cephalic-phase insulin responses (CPIRs) to specific sounds or times of the day that predict food availability. The present study asked whether mice can condition a CPIR to the flavor of sapid solutions that produce postoral glucose stimulation. To this end, we subjected C57BL/6 mice to one of six experimental protocols. We varied both the duration of the five training sessions (i.e., 23 h or 1 h) and the nature of the training solution. In Experiment 1, consumption of a 0.61% saccharin solution was paired with IG co-infusion of a 16% glucose solution. In Experiments 2-6, the mice consumed a training solution containing a mixture of 0.61% saccharin + 16% glucose, 32% sucrose, 32% maltodextrin, flavored 32% maltodextrin, or 16% maltodextrin. We subsequently asked whether consumption of any of these fluids conditioned a CPIR to a test solution that produced a similar flavor, but which did not elicit a CPIR in naïve mice. The mice did condition a CPIR, but only to the solutions containing 32% maltodextrin. We attribute this conditioning to postoral actions of the concentrated maltodextrin solutions.
Subject(s)
Glucose , Insulin , Mice, Inbred C57BL , Polysaccharides , Animals , Insulin/blood , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Male , Mice , Blood Glucose/metabolism , Saccharin/administration & dosage , Flavoring Agents/administration & dosage , Taste , Postprandial Period , Insulin Secretion/drug effectsSubject(s)
Anticoagulants , Factor Xa Inhibitors , Fondaparinux , Heart Valve Prosthesis , Humans , Fondaparinux/administration & dosage , Fondaparinux/therapeutic use , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/therapeutic use , Male , Aged , Female , Anticoagulants/administration & dosage , Middle Aged , Polysaccharides/administration & dosage , Polysaccharides/therapeutic use , Aged, 80 and overABSTRACT
Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were â4)-ß-D-Manp(1â, â4)-ß-Glcp(1â, ß-D-Manp(1â, and ß-D-Glcp(1â. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1ß to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.
Subject(s)
Dendrobium , Fermentation , Liver Diseases, Alcoholic , Liver , Polysaccharides , Animals , Mice , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Dendrobium/chemistry , Male , Liver Diseases, Alcoholic/prevention & control , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/drug therapy , Humans , Liver/metabolism , Liver/drug effects , Protective Agents/pharmacology , Protective Agents/chemistry , Protective Agents/administration & dosage , Lactobacillales/metabolism , Lactobacillales/genetics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/administration & dosageABSTRACT
Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.
Subject(s)
Disease Models, Animal , Nanoparticles , Polysaccharides , Spiramycin , Toxoplasmosis, Animal , Animals , Spiramycin/therapeutic use , Spiramycin/administration & dosage , Mice , Polysaccharides/administration & dosage , Polysaccharides/therapeutic use , Polysaccharides/pharmacology , Nanoparticles/chemistry , Toxoplasmosis, Animal/drug therapy , Toxoplasma/drug effects , Female , Brain/parasitology , Brain/pathology , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/therapeutic use , Toxoplasmosis/drug therapy , Toxoplasmosis/parasitology , Drug CarriersABSTRACT
Skin aging occurs naturally as essential skin components gradually decline, leading to issues such as fine lines, wrinkles, and pigmentation. Fucoidan, a natural bioactive compound, holds potential for addressing these age-related concerns. However, its hydrophilic nature and substantial molecular weight hinder its absorption into the skin. In this study, we utilized polyvinyl pyrrolidone K30 (PVP) and polyvinyl alcohol (PVA) as polymers to fabricate dissolving microneedles loaded with fucoidan (DMN-F). The DMN-F formulations were examined for physical characteristics, stability, permeability, toxicity, and efficacy in animal models. These formulations exhibited consistent polymer blends with a conical structure and uniform cone-shaped design. Microneedle structure and penetration capability gradually decreased with increasing fucoidan concentration, with storage recommended at approximately 33 % relative humidity (RH). Ex vivo studies showed that DMN-F efficiently delivered up to 95.03 ± 2.36 % of the total fucoidan concentration into the skin. In vivo investigations revealed that DMN-F effectively reduced wrinkles, improved skin elasticity, maintained moisture levels, and increased epidermal thickness. Histological images provided additional evidence of DMN-F's positive effects on these aging parameters. The results confirm that the DMN-F formulation effectively delivers fucoidan into the skin, allowing it to treat and mitigate signs of aging.
Subject(s)
Administration, Cutaneous , Drug Delivery Systems , Needles , Polysaccharides , Skin Aging , Skin , Animals , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Skin Aging/drug effects , Mice , Drug Delivery Systems/methods , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Povidone/chemistry , Polyvinyl Alcohol/chemistry , Female , SolubilityABSTRACT
Sepsis-associated acute lung injury (ALI) poses a significant threat, characterized by inflammation and oxidative damage. Effective drugs targeting these aspects with reliable drug delivery systems are vital for ALI management. This study aimed to evaluate the influence of algal polysaccharides (APs) with aerosolized drug delivery in ALI mice and clarify the underlying mechanism. To induce the sepsis-associated acute lung injury (ALI) model, mice were administered intraperitoneal injections of 10 mg/kg LPS for 48 h in vivo. ALI mice received APs via atomization to arrive at different sites within the lungs. Lung tissue samples and bronchoalveolar lavage fluid (BALF) were collected to access lung injury parameters. Concurrently, western blotting, H&E staining, and immunofluorescence (IF) were applied to investigate the specific impact of APs on ALI. The results showed that APs protect lung tissue against ALI by inhibiting inflammation and mitigating oxidative stress-induced damage. This study highlights promising avenues for ALI intervention using natural compounds with anti-inflammatory and antioxidant properties.
Subject(s)
Acute Lung Injury , Anti-Inflammatory Agents , Lung , Oxidative Stress , Polysaccharides , Animals , Oxidative Stress/drug effects , Polysaccharides/therapeutic use , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Administration, Inhalation , Mice , Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Male , Lung/drug effects , Lung/pathology , Lung/metabolism , Pneumonia/drug therapy , Disease Models, Animal , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/chemistry , Lipopolysaccharides , Antioxidants/therapeutic use , Antioxidants/pharmacology , Antioxidants/administration & dosage , Mice, Inbred C57BL , Sepsis/drug therapy , Aerosols , Inflammation/drug therapy , HumansABSTRACT
Avian influenza virus subtype H9N2 has the ability to infect birds and humans, further causing significant losses to the poultry industry and even posing a great threat to human health. Oral vaccine received particular interest for preventing majority infection due to its ability to elicit both mucosal and systemic immune responses, but their development is limited by the bad gastrointestinal (GI) environment, compact epithelium and mucus barrier, and the lack of effective mucosal adjuvants. Herein, we developed the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) as an adjuvant for H9N2 vaccine. Encouragingly, CDP-DFNS facilitated the proliferation of T and B cells, and further induced the activation of T lymphocytes in vitro. Moreover, CDP-DFNS/H9N2 significantly promoted the antigen-specific antibodies levels in serum and intestinal mucosal of chickens, indicating the good ability to elicit both systemic and mucosal immunity. Additional, CDP-DFNS facilitate the activation of CD4 + and CD8 + T cells both in spleen and intestinal mucosal, and the indexes of immune organs. This study suggested that CDP-DFNS may be a new avenue for development of oral vaccine against pathogens that are transmitted via mucosal route.
Subject(s)
Adjuvants, Immunologic , Chickens , Immunity, Mucosal , Influenza A Virus, H9N2 Subtype , Influenza Vaccines , Influenza in Birds , Nanoparticles , Polysaccharides , Silicon Dioxide , Animals , Influenza A Virus, H9N2 Subtype/immunology , Influenza A Virus, H9N2 Subtype/drug effects , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/immunology , Silicon Dioxide/administration & dosage , Silicon Dioxide/chemistry , Nanoparticles/administration & dosage , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Immunity, Mucosal/drug effects , Influenza in Birds/prevention & control , Influenza in Birds/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Administration, Oral , Intestinal Mucosa/immunology , Intestinal Mucosa/drug effects , Antibodies, Viral/blood , Antibodies, Viral/immunologyABSTRACT
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.
Subject(s)
Drug Delivery Systems , Emulsions , Fluorouracil , Gels , Pectins , Polysaccharides, Bacterial , Animals , Fluorouracil/administration & dosage , Fluorouracil/chemistry , Polysaccharides, Bacterial/chemistry , Tissue Adhesions/prevention & control , Male , Pectins/chemistry , Pectins/administration & dosage , Drug Liberation , Postoperative Complications/prevention & control , Mice , Humans , Rats, Sprague-Dawley , Rats , Delayed-Action Preparations , Polysaccharides/chemistry , Polysaccharides/administration & dosageABSTRACT
In this study, we investigated the effects of supplemental Glycyrrhiza polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at 28 days of age were randomly allocated to three groups with five replicates per treatment. Piglets were fed the following diets for 28 days: (1) CON (control group), basal diet; (2) G500, CON + 500 mg/kg GCP; (3) G1000, CON + 1000 mg/kg GCP. The results showed that supplementation with 1000 mg/kg GCP increased the average daily gain (ADG) and decreased the feed-to-gain ratio (F/G) (P < 0.05). Serum diamine oxidase (DAO) and D-lactic acid (DL-A) levels were lower in the G1000 group (P < 0.05). Dietary GCP 1000 mg/kg improved mucosal trypsin activity in the duodenum, jejunum and ileum and increased lipase and amylase activity in the jejunum (P < 0.05). Moreover, in the G1000 group, ZO-1, claudin 1 and occludin levels were increased in the jejunum mucosa, whereas interleukin-1ß (IL-1ß) and IL-6 levels were decreased (P < 0.05). The 16S rRNA gene analysis indicated that dietary 1000 mg/kg GCP altered the jejunal microbial community, with increased relative abundances of beneficial bacteria. In conclusion, dietary GCP 1000 mg/kg can improve growth performance, digestive enzyme activity, intestinal immunity, barrier function and microbial community in weaned piglets.
Subject(s)
Animal Feed , Dietary Supplements , Glycyrrhiza , Polysaccharides , Weaning , Animals , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Swine/growth & development , Animal Feed/analysis , Glycyrrhiza/chemistry , Intestines/drug effects , Diet/veterinary , Gastrointestinal Microbiome/drug effects , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , MaleABSTRACT
Fucoidan has shown better effects on the improvement of acute ulcerative colitis (UC). However, the specific mechanisms by which fucoidan improves UC-related behavioral disorders in aged mice, especially its effect on the gut-brain axis, remain to be further explored. C57BL/6 male mice aged 8 months were gavaged with 400 or 100 mg/kg bw day fucoidan for five consecutive weeks, with UC being induced by ad libitum to dextran sulfate sodium (DSS) solution in the fifth week. The results showed that fucoidan ameliorated UC and accompanying anxiety- and depressive-like behaviors with downregulated expressions of (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate-specific protease-1 (Caspase-1) and interlekin-1ß (IL-1ß), and elevated mRNA levels of brain-derived neurotrophic factor (Bdnf) and postsynaptic-density protein 95 (Psd-95) in cortex and hippocampus. Furthermore, fucoidan improved the permeability of intestinal barrier and blood-brain barrier and restored the abnormal structure of the gut microbiota with a significantly decreased ratio of Firmicutes to Bacteroidota (F/B) and obviously increased abundance of Akkermansia. As a diet-derived bioactive ingredient, fucoidan might be a better alternative for the prevention of UC and accompanying anxiety- and depressive-like behaviors.
Subject(s)
Anxiety , Colitis, Ulcerative , Depression , Dextran Sulfate , Mice, Inbred C57BL , Polysaccharides , Animals , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Polysaccharides/chemistry , Male , Dextran Sulfate/adverse effects , Mice , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/chemically induced , Depression/drug therapy , Depression/metabolism , Anxiety/drug therapy , Humans , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Gastrointestinal Microbiome/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Caspase 1/metabolism , Caspase 1/genetics , Disease Models, Animal , Hippocampus/metabolism , Hippocampus/drug effects , Behavior, Animal/drug effectsABSTRACT
BACKGROUND: Garlic polysaccharides (GPs) constitute over 75% of the dry weight of garlic. They are characterized by fructan with a 2,1-ß-d-Fruf backbone and 2,6-ß-d-Fruf branches. Studies have suggested a role for GPs in regulating gut microbiota but whether they possess a comprehensive function in maintaining intestinal well-being and can serve as effective prebiotics remains unknown. To explore this, varied doses of GPs (1.25-5.0 g kg-1 body weight) and inulin (as a positive control) were administered to Kunming mice via gavage, and their effects on the intestinal epithelial, chemical, and biological barriers were assessed. A constipation model was also established using loperamide to investigate the potential effects of GPs on the relief of constipation. RESULTS: Administration of GPs significantly upregulated expression of tight-junction proteins and mucins in Kunming mouse small-intestine tissue. Garlic polysaccharides elevated cecal butyric acid content, reduced the abundance of Desulfobacterota, and decreased the ratio of Firmicutes to Bacteroidetes (the F/B ratio). Garlic polysaccharides also promoted the growth of Bacteroides acidifaciens and Clostridium saccharogumia. Tax4Fun functional predictions suggested the potential of GPs to prevent human diseases, reducing the risk of insulin resistance, infectious diseases, and drug resistance. Garlic polysaccharides also exhibited a beneficial effect in alleviating loperamide-induced constipation symptoms by enhancing small intestinal transit, softening stool consistency, accelerating bowel movements, and promoting the release of excitatory neurotransmitters. CONCLUSIONS: These findings highlight the important role of GPs in maintaining gut fitness by enhancing intestinal barrier function and peristalsis. Garlic polysaccharides are promising prebiotics, potentially contributing to overall intestinal well-being and health. © 2024 Society of Chemical Industry.
Subject(s)
Constipation , Fructans , Garlic , Gastrointestinal Microbiome , Oligosaccharides , Plant Extracts , Prebiotics , Animals , Constipation/drug therapy , Constipation/chemically induced , Mice , Garlic/chemistry , Gastrointestinal Microbiome/drug effects , Male , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/pharmacology , Prebiotics/administration & dosage , Fructans/chemistry , Oligosaccharides/administration & dosage , Bacteria/classification , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/genetics , Humans , Intestinal Mucosa/metabolism , Intestines/drug effects , Intestines/microbiology , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Intestine, Small/metabolism , Intestine, Small/microbiology , Intestine, Small/drug effects , Animals, Outbred StrainsABSTRACT
BACKGROUND: Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). RESULTS: QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6ß levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION: In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.
Subject(s)
Colitis, Ulcerative , Dextran Sulfate , Polysaccharides , Zinc , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Animals , Dextran Sulfate/adverse effects , Mice , Zinc/administration & dosage , Zinc/metabolism , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Male , Humans , Tea/chemistry , Colon/metabolism , Colon/drug effects , Colon/pathology , Disease Models, Animal , Camellia sinensis/chemistry , Gastrointestinal Microbiome/drug effects , Mice, Inbred C57BL , Fatty Acids, Volatile/metabolism , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , SulfatesABSTRACT
During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.
Subject(s)
Arthritis, Rheumatoid , Macrophages , Needles , Polysaccharides , Reactive Oxygen Species , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Animals , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Mice , Reactive Oxygen Species/metabolism , Macrophages/metabolism , Macrophages/drug effects , Polymers/chemistry , RAW 264.7 Cells , Inflammation/drug therapy , Humans , Nanoparticles/chemistry , Drug Delivery Systems , Cytokines/metabolism , MorphinansABSTRACT
Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon -targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.
Subject(s)
Colitis, Ulcerative , Drug Delivery Systems , Hydrogels , Colitis, Ulcerative/drug therapy , Hydrogels/chemistry , Hydrogels/administration & dosage , Drug Delivery Systems/methods , Animals , Tumor Necrosis Factor-alpha , Humans , Administration, Oral , Colon/metabolism , Colon/drug effects , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Administration, Rectal , Area Under CurveABSTRACT
The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.
Subject(s)
Anti-Inflammatory Agents , Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Insulin , Polysaccharides , Animals , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Blood Glucose/drug effects , Blood Glucose/analysis , Administration, Oral , Insulin/administration & dosage , Insulin/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Mice , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/pharmacokinetics , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Male , Vitamin B 12/administration & dosage , Nanoparticles/administration & dosage , Drug Liberation , Drug Carriers/chemistry , HumansABSTRACT
Little information is available on the effect of Hericium erinaceus polysaccharides (HEP) on laying hens, especially on improving liver and ovarian health and function. Therefore, this study was conducted to investigate the impacts of HEP on liver and ovarian function to delay the decline in the laying performance of aged hens. A total of 360 fifty-eight-wk-old laying hens were randomly allocated to 4 treatments, with 6 replicates of 15 birds each. After 2 wk of adaptation, the birds were fed basal diet (CON) or basal diets supplemented with 250, 500, and 750 mg/kg of HEP (HEP250, HEP500, and HEP 750, respectively) for 12 wk. The results showed that, compared with CON, hens fed HEP had significantly increased laying performance (P < 0.05) and promoted follicle development, as evidenced by the increased numbers of hierarchical follicles, small follicles, and total follicles (P < 0.05). Birds fed 500 mg/kg of HEP improved the liver function by increasing T-AOC activity (P < 0.05) and decreasing hepatic oxidative stress and inflammatory responses (inflammatory cell infiltration) caused by aging. The lipid metabolism was improved, and yolk precursor synthesis was promoted in the liver of HEP-treated laying hens by upregulating the mRNA expression of FAS, MTTP, PPAR-α, APOVLDL-â ¡, and VTG-â ¡ (P < 0.05). In addition, HEP significantly decreased ovarian inflammation by regulating the mRNA levels of NF-κB, IL-1ß, IL-6, and TNF-α (P < 0.05). As a result, the contents of E2, LH, and FSH in serum and the gene expression of ERα of the liver and FSHR of the ovary increased in HEP-treated hens (P < 0.05). In conclusion, dietary HEP supplementation exhibited potential hepatic and ovarian protective effects, thereby increasing the laying performance of aged hens by enhancing reproductive hormone secretion hormone secretion and promoting yolk precursor synthesis and follicle development via the liver-blood-ovary axis. The optimal supplementation level of HEP in aged hens was 500 mg/kg.
Subject(s)
Animal Feed , Chickens , Diet , Liver , Animals , Chickens/physiology , Female , Liver/drug effects , Liver/metabolism , Animal Feed/analysis , Diet/veterinary , Ovarian Follicle/drug effects , Dietary Supplements/analysis , Egg Yolk/chemistry , Random Allocation , Ovary/drug effects , Ovary/metabolism , Dose-Response Relationship, Drug , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Reproduction/drug effectsABSTRACT
Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.
Subject(s)
Diet, High-Fat , Lipogenesis , Lipolysis , Mice, Inbred C57BL , Polysaccharides , Animals , Lipogenesis/drug effects , Mice , Lipolysis/drug effects , Male , Diet, High-Fat/adverse effects , Humans , Polysaccharides/pharmacology , Polysaccharides/administration & dosage , Sirtuin 1/metabolism , Sirtuin 1/genetics , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/genetics , Kidney Tubules/metabolism , Kidney Tubules/drug effects , Camellia sinensis/chemistry , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Tea/chemistry , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/geneticsABSTRACT
BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.
Subject(s)
Administration, Cutaneous , Drug Liberation , Niacin , Polysaccharides , Rats, Wistar , Skin Absorption , Skin , Animals , Rats , Niacin/administration & dosage , Niacin/chemistry , Niacin/pharmacology , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Flushing/chemically induced , Tensile Strength , Male , Drug Delivery Systems/methods , Tamarindus/chemistry , Polymers/chemistryABSTRACT
Wound healing following skin tumour surgery still remains a major challenge. To address this issue, polysaccharide-loaded nanofibrous mats have been engineered as skin patches on the wound site to improve wound healing while simultaneously eliminating residual cancer cells which may cause cancer relapse. The marine derived polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were blended with polydioxanone (PDX) nanofibers due to their inherent anti-cancer activity conferred by the sulphate groups as well as their immunomodulatory properties which can reduce inflammation resulting in accelerated wound healing. KCG and FUC were released sustainably from the blend nanofibers via the Korsmeyer-Peppas kinetics. MTT assays, live/dead staining and SEM images demonstrated the toxicity of KCG and FUC towards skin cancer MP 41 cells. In addition, MP 41 cells showed reduced metastatic potential when grown on KCG or FUC containing mats. Both KCG and FUC were non- cytotoxic to healthy L 929 fibroblast cells. In vivo studies on healthy Wistar rats confirmed the non-toxicity of the nanofibrous patches as well as their improved and scarless wound healing potential. In vivo studies on tumour xenograft model further showed a reduction of 7.15 % in tumour volume in only 4 days following application of the transdermal patch.