Chitosan-Stabilized Selenium Nanoparticles Alleviate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Modulating the Gut Barrier Function and Microbiota.

Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.

Megalin-targeted acetylcysteine polymeric prodrug ameliorates ischemia-reperfusion-induced acute kidney injury.

Acute kidney injury (AKI), a condition associated with reactive oxygen species (ROS), causes high mortality in clinics annually. Active targeted antioxidative therapy is emerging as a novel strategy for AKI treatment. In this study, we developed a polymeric prodrug that targets the highly expressed Megalin receptor on proximal tubule cells, enabling direct delivery of N-Acetylcysteine (NAC) for the treatment of ischemia reperfusion injury (IRI)-induced AKI. We conjugated NAC with low molecular weight chitosan (LMWC), a biocompatible and biodegradable polymer consisting of glucosamine and N-acetylglucosamine, to enhance its internalization by tubular epithelial cells. Moreover, we further conjugated triphenylphosphonium (TPP), a lipophilic cation with a delocalized positive charge, to low molecular weight chitosan-NAC in order to enhance the distribution of NAC in mitochondria. Our study confirmed that triphenylphosphonium-low molecular weight chitosan-NAC (TLN) exhibits remarkable therapeutic effects on IRI-AKI mice. This was evidenced by improvements in renal function, reduction in oxidative stress, mitigation of pathological progress, and decreased levels of kidney injury molecule-1. These findings suggested that the polymeric prodrug TLN holds promising potential for IRI-AKI treatment.

Low molecular weight chitosan based GSH-responsive self-assembled cationic micelle with enhanced anti-tumor effect by combining oxidative damage and chemotherapy.

A novel cationic lipoic acid grafted low molecular weight chitosan (LCNE-LA) conjugate was constructed and further self-assembled into GSH-responsive cationic nanocarrier to achieve better antitumor effect by combining encapsulated chemotherapy and oxidative damage induced by ROS. The resultant LCNE-LA cationic micelle exhibited favorable physicochemical properties (low CMC, small size, positively zeta potential and good stability), excellent biosafety and desired redox sensitivity. Next, doxorubicin (Dox) was embedded into hydrophobic core to form stable Dox/LCNE-LA micelle that had superior loading capacity. The GSH-induced release behavior, cellular uptake ability, ROS generation and GSH consumption capacity and in vitro antitumor activity of Dox/LCNE-LA micelle were systematically evaluated. Consequently, Dox/LCNE-LA cationic micelle with positively charged could efficiently enter into cancer cell and redox-sensitive release Dox via disulfide-thiol exchange reaction, which usually expend abundant GSH and disrupt redox homeostasis. Studies further confirmed that Dox/LCNE-LA micelle could increase ROS and reduced GSH content which might cause oxidative damage to tumor cell. Antitumor activity indicated that Dox/LCNE-LA micelle achieved an excellent cancer-killing effect, which might be attributed to combination treatment of Dox and ROS induce oxidative damage. Overall, this research was expected to provide a platform for antitumor treatment by triggering Dox release and promoting ROS generation.

Self-assembled low molecular weight chitosan-based cationic micelle for improved water solubility, stability and sustained release of α-tocopherol.

New amphiphilic low molecular weight chitosan-graft-nicotinic acid bearing decyl groups (LCND) was synthesized by two-step reaction and spontaneously assembled into cationic micelle by ultra-sonication method to improve water solubility and photostability properties of α-tocopherol. The chemical structure of LCND was characterized and physical properties of cationic micelle were evaluated. Results displayed that cationic micelle exhibited strong self-assemble ability with nanoscale spherical morphology and showed best loading ability with loading content of 18.50% when the feeding ratio of LCND to α-tocopherol reached 10:3. Meanwhile, the greatly enhanced water solubility, photostability and sustained release behavior of α-tocopherol in cationic micelle were observed. The cumulative release of α-tocopherol in cationic micelle reached up 82.18% within 96 h while free α-tocopherol was completely released within 10 h. Additionally, release kinetics models were also fitted. The LCND cationic micelle could be promising nanocarrier for improving the physicochemical properties of α-tocopherol in food fields.

Strong tissue adhesive polyelectrolyte complex powders based on low molecular weight chitosan for acute hemorrhage control.

Self-gelling and bioadhesive powders offered promising effective hemostats to suit irregularly shaped, complex and non-compressible wounds for clinical applications. In the current study, chitosan based polyelectrolyte complex coacervate were simply prepared by mixing high concentrations (10 %) of low molecular weight chitosan (CS) and polyacrylic acid (PAA) solutions. Obtained by lyophilization, the physical cross-linked polyelectrolyte complex powders would form a gel within 5 s upon hydration, which demonstrated excellent mechanical properties, significant antibacterial activities, strong and lasting adhesion on wet tissues in physiological environment. In vitro blood clotting assays showed that the CS/PAA powders could remarkably aggregate blood cells and accelerate blood clotting process. As studied by diverse hemorrhage models, including rat tail, liver and heart injuries and dog incision, CS/PAA powders significantly facilitated the decrease of blood loss as well as hemostatic time by creating robust physical barriers and promoting blood clot formation on the bleeding sites. These outstanding properties in terms of easy preparation, rapid self-gelling, strong wet adhesion, effective hemostasis and shape-adaptability endowed CS/PAA polyelectrolyte complex powders with great potential in managing acute hemorrhage of non-compressible trauma.

Bilirubin Nanomedicine Rescues Intestinal Barrier Destruction and Restores Mucosal Immunity in Colitis.

Inflammatory bowel disease (IBD) manifests as intestinal barrier destruction, mucosal immunity dysregulation, and disrupted gut microbiome homeostasis. Conventional anti-inflammatory medications for IBD therapy partially alleviate symptoms but are unable to restore normal barrier and immune function. Here, we report a nanomedicine comprising bilirubin (BR)-attached low-molecular-weight, water-soluble chitosan nanoparticles (LMWC-BRNPs), that promotes restoration of the intestinal barrier, mucosal immunity, and the gut microbiome, thereby exerting robust therapeutic efficacy. In a mouse model of dextran sulfate sodium salt (DSS)-induced colitis, orally administered LMWC-BRNPs were retained in the GI tract much longer than other nonmucoadhesive BRNPs owing to the mucoadhesiveness of LMWC via electrostatic interaction. Treatment with LMWC-BRNPs led to considerable recovery of the damaged intestinal barrier compared with the current IBD medication, 5-aminosalicylic acid (5-ASA). Orally administered LMWC-BRNPs were taken up by pro-inflammatory macrophages and inhibited their activity. They also concurrently increased the population of regulatory T cells, thereby leading to the recovery of dysregulated mucosal immunity. An analysis of the gut microbiome revealed that LMWC-BRNPs treatment significantly attenuated the increase Turicibacter, an inflammation-related microorganism, resulting in protection of gut microbiome homeostasis. Taken together, our findings indicate that LMWC-BRNPs restored normal functions of the intestine and have high potential for use as a nanomedicine for IBD therapy.

Application of depolymerized chitosan in crop production: A review.

Currently, chitosan (CHT) is well known for its uses, particularly in veterinary and agricultural fields. However, chitosan's uses suffer greatly due to its extremely solid crystalline structure, it is insoluble at pH levels above or equal to 7. This has sped up the process of derivatizing and depolymerizing it into low molecular weight chitosan (LMWCHT). As a result of its diverse physicochemical as well as biological features which include antibacterial activity, non-toxicity, and biodegradability, LMWCHT has evolved into new biomaterials with extremely complex functions. The most important physicochemical and biological property is antibacterial, which has some degree of industrialization today. CHT and LMWCHT have potential due to the antibacterial and plant resistance-inducing properties when applied in crop production. This study has highlighted the many advantages of chitosan derivatives as well as the most recent studies on low molecular weight chitosan applications in crop development.

A low-molecular-weight chitosan fluorometric-based assay for evaluating antiangiogenic drugs.

Low-molecular-weight chitosan (LMWCS) damaged cell membranes in zebrafish showed its possibility to release reporter proteins for detection. In this study, we developed a simple fluorometric-based assay for the evaluation of clinical antiangiogenic drugs using LMWCS and Tg(fli1:EGFP) transgenic zebrafish, which expressed green-fluorescence protein (GFP) in the endothelial cells of blood vessel. In vitro stable and transiently transfected cell lines was released luciferase and green fluorescent protein (GFP) for intensity evaluation upon LMWCS fluorometric-based assay. In vivo Tg(fli1:EGFP) transgenic zebrafish was also released GFP from endothelial cells of blood vessels and show an increase of fluorescent intensity upon LMWCS fluorometric-based assay. Treatment with the clinical antiangiogenic drug sorafenib and analyzed by LMWCS fluorometric-based assay showed significantly reduction of angiogenesis. Furthermore, treatment with 2 µM sorafenib showed a significant reduction in angiogenesis of the intersegmental vein (ISV) and dorsal longitudinal anastomotic vessels (DLAV) in Tg(fli1:EGFP) transgenic zebrafish. Fluorescence intensity reduction from 2 µM sorafenib was used as a factor in the LMWCS fluorescence-based assay for relative antiangiogenic evaluation. Relative angiogenesis evaluation of the clinical drugs axitinib, cabozantinib, and regorafenib showed a significant reduction. Collectively, this study provided a simple, convenient, and rapid LMWCS fluorometric-based assay for evaluating angiogenic drugs using transgenic zebrafish.

Effect of Hydrophobic Chain Length in Amphiphilic Chitosan Conjugates on Intracellular Drug Delivery and Smart Drug Release of Redox-Responsive Micelle.

Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.

Production of Low Molecular Weight Chitosan Using a Combination of Weak Acid and Ultrasonication Methods.

Low molecular weight chitosan (LMWC) has higher solubility and lower viscosity allowing for a wider pharmaceutical application compared to high molecular weight chitosan. LMWC chitosan can be obtained through a chitosan depolymerization process. This research aimed to produce LWMC using the combination of formic acid and ultrasonication method with the optimal condition of the depolymerization process. The chitosan depolymerization method was performed by combining formic acid and ultrasonication. The optimum conditions of the depolymerization process were obtained using the Box-Behnken design. The LMWC obtained from depolymerization was characterized to identify its yield, degree of deacetylation, the molecular weight, structure, morphology, thermal behavior, and crystallinity index. Results: The characterization results of LWMC obtained from the depolymerization process using the optimum conditions showed that the yield was 89.398%; the degree of deacetylation was 98.076%; the molecular weight was 32.814 kDa; there was no change in the chemical structure, LWMC had disorganized shape, there was no change in the thermal behavior, and LWMC had a more amorphous shape compared to native chitosan. Conclusion: The production of LWMC involving depolymerization in the presence of weak acid and ultrasonication can be developed by using the optimal condition of the depolymerization process.

Anticancer therapeutic potential of 5-fluorouracil and nisin co-loaded chitosan coated silver nanoparticles against murine skin cancer.

Cancer is a major health concern worldwide as conventional treatment modalities face several limitations such as drug resistance, toxicity etc. To overcome such deficits, combination therapy involving anticancer peptides and chemodrugs is being considered as an attractive strategy. Therefore, present study developed, characterized and evaluated the anticancer potential of a single nanoconstruct comprising of oligomeric chitosan coated silver nanoparticles co-loaded with nisin and 5-florouracil (5-FU/nisin-CHI-AgNPs) against DMBA/TPA-induced murine skin cancer. It was fabricated using wet reduction method of silver salt to form silver nanoparticles followed sequentially by oligomeric chitosan coating, nisin conjugation to deacetylated units of chitosan oligomers (EDC/NHS chemistry) and physical loading of 5-FU. Biophysical characterisation studies revealed that the developed nanoconstruct had UV-visible absorption maxima at 420 nm, zeta potential of + 32.90 mV and 72.39 nm particle size (TEM analysis). In vivo anticancer therapeutic potential was assessed in terms of tumor statistics, histopathological, scanning electron microscopic analyses and testing oxidant/antioxidant status which exhibited marked reduction both in mean tumor volume (68.34 %) and mean tumor burden (82.39 %); restored skin histoarchitecture and improved oxidant/antioxidant status. Interestingly, anticancer therapeutic potential of nisin and 5-florouracil was found to be enhanced in vivo when bound on single composite nanoconstruct. The study forms a basis for developing synergetic single platforms against variety of cancers.

Addition time plays a major role in the inhibitory effect of chitosan on the production of Pseudomonas aeruginosa virulence factors.

Pseudomonas aeruginosa is a gram-negative bacterium capable of forming persistent biofilms that are extremely difficult to eradicate. The species is most infamously known due to complications in cystic fibrosis patients. The high mortality of cystic fibrosis is caused by P. aeruginosa biofilms occurring in pathologically overly mucous lungs, which are the major cause facilitating the organ failure. Due to Pseudomonas biofilm-associated infections, remarkably high doses of antibiotics must be administered, eventually contributing to the development of antibiotic resistance. Nowadays, multidrug resistant P. aeruginosa is one of the most terrible threats in medicine, and the search for novel antimicrobial drugs is of the utmost importance. We have studied the effect of low molecular weight chitosan (LMWCH) on various stages of P. aeruginosa ATCC 10145 biofilm formation and eradication, as well as on production of other virulence factors. LMWCH is a well-known naturally occurring agent with a vast antimicrobial spectrum, which has already found application in various fields of medicine and industry. LMWCH at a concentration of 40 mg/L was able to completely prevent biofilm formation. At a concentration of 60 mg/L, this agent was capable to eradicate already formed biofilm in most studied times of addition (2-12 h of cultivation). LMWCH (50 mg/L) was also able to suppress pyocyanin production when added 2 and 4 h after cultivation. The treatment resulted in reduced formation of cell clusters. LMWCH was proved to be an effective antibiofilm agent worth further clinical research with the potential to become a novel drug for the treatment of P. aeruginosa infections.

A novel low-molecular-weight chitosan/gamma-polyglutamic acid polyplexes for nucleic acid delivery into zebrafish larvae.

Many challenges, such as virus infection, extreme weather and long cultivation periods, during the development of fish larvae have been observed, especially in aquaculture. Gene delivery is a useful method to express functional genes to defend against these challengers. However, the methods for fish larvae are insufficient. In our earlier report, low-molecular-weight chitosan (LMWCS) showed a strong positive charge and may be useful for polyplex formulation. Herein, we present a simple self-assembly of LMWCS polyplexes (LMWCSrNPs) for gene delivery into zebrafish larvae. Different weight ratios of LMWCS/gamma-polyglutamic acid (γ-PGA)/plasmid DNA were analyzed by gel mobility assay. Delivery efficiency determined by green fluorescent protein (GFP) expression in zebrafish liver (ZFL) cells showed that delivery efficiency at a weight ratio of 20:8:1 was higher than others. Zeta potential and transmission electron microscopy (TEM) analysis showed that the round shape of the particle size varied. In our earlier reports, IRF9S2C could induce interferon-stimulated gene (ISG) expression to induce innate immunity in zebrafish and pufferfish. Further delivery of pcDNA3-IRF9S2C-HA plasmid DNA into ZFL cells and zebrafish larvae by LMWCSrNP successfully induced ISG expression. Collectively, LMWCSrNP could be a novel gene delivery system for zebrafish larvae and might be used to improve applications in aquaculture.

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Effect of Hydroxymethylfurfural and Low-Molecular-Weight Chitosan on Formation of Acrylamide and Hydroxymethylfurfural during Maillard Reaction in Glucose and Asparagine Model Systems.

The aim of this research was to investigate the effects of the addition of 0.5% hydroxymethylfurfural (HMF) and low molecular chitosan on acrylamide and HMF formation in a food model system, which contains 0.5% glucose, asparagine, and HMF within 30 min of heating at 180 °C. At an interval of 10 min, all solutions were evaluated in the following aspects: reducing sugar, asparagine, acrylamide, HMF content, pH, Maillard reaction products, kinematic viscosity, and color. After heating for 10 min, the kinematic viscosity of solutions containing chitosan reduced significantly. The values of the acrylamide, HMF, and absorbance increased at OD294 and OD420 (optical density measured at 294 nm and 420 nm) of solutions. Experimental results showed that low-molecular-weight chitosan might be hydrolyzed into much lower molecular weight, followed by the decrease in kinematic viscosity of the solution at pH lower than 6 and the increase in the formation of acrylamide after heating for 30 min.

Preparation of low molecular chitosan by microwave-induced plasma desorption/ionization technology.

Compared with high molecular weight chitosan (HMWC), low molecular weight chitosan (LMWC) has better solubility and biological activity. However, there is no quick and environmentally friendly to prepare low molecular chitosan. In this study, microwave induced plasma desorption/ionization (MIPDI) was used for the first time to prepare LMWC through the degradation processes of HMWC. The results showed that MIPDI has the most abundant ∙OH content at the gas-liquid interface, and the active particles represented by ∙OH can degrade chitosan with a molecular weight of 540 KDa into soluble chitosan (≤ 10 KDa), and the yield of soluble chitosan can reach 61% in 60 min. Moreover, a series of characterization results showed that the chain structure and crystal structure gradually degraded as the treatment time increased while the chemical structure of chitosan did not change significantly. Antibacterial experiments also indicated that the antimicrobial property of LMWC obtained by MIPDI degradation was improved. In short, this method has proven to be a new, fast and green processing method for the preparation of low molecular chitosan.

The immunosuppressive effects of low molecular weight chitosan on thymopentin-activated mice bearing H22 solid tumors.

In the present study, the low molecular weight of chitosan (CS) was prepared and its activity on thymopentin-activated mice bearing H22 solid tumors was further researched. The purity and molecular weight of CS were determined by UV and HPGPC spectra, and its immunosuppressive effects on H22 tumor-bearing mice were evaluated through determination on immune organs, cells and cytokines. Results showed that CS contained little impurities with the average molecular weight of 1.20 × 104 Da. The in vivo antitumor experiments demonstrated that CS facilitated to destroy immune organs (thymuses and spleens), suppress immune cells (lymphocytes, macrophages and NK cells) activities and reduce immune-related cytokines (TNF-α, IFN-γ, IL-2 and IL-4) expressions of H22 tumor-bearing mice even with simultaneous TP5 stimulation. Our data suggested that CS could not be applied to improve immune response in cancer-bearing patients, but might be employed for treatments on autoimmune diseases or organ transplant patients.

Intermolecular interactions of chitosan: Degree of acetylation and molecular weight.

The degree of acetylation (DA), which determines as the molar proportion of N-acetyl-D-glucosamine units on chitosan, characterizes the physical, chemical, and biological properties of chitosan. Thus, DA can be a critical factor in the utilization of chitosan. Nevertheless, quantitative studies on the molecular interactions of chitosan as a function of DA are lacking. Here, we directly measured the molecular interaction (adhesion and cohesion) of molecularly thin chitosan films, dependent on the molecular weight and DA, using a surface forces apparatus. Using low molecular weight (LMW, ∼5 kDa) and high molecular weight (HMW, ∼135 kDa) chitosan, we obtained several DA ranges through a reacetylation method. The interactions of LMW chitosan were greatly influenced by the intrinsic charge of the chitosan units, whereas for HMW chitosan, chain flexibility was found to be the major factor affecting molecular interaction Taken together, our comprehensive data provides a holistic understanding of the interaction mechanism of chitosan.

Low molecular weight chitosan-cyanocobalamin nanoparticles for controlled delivery of ciprofloxacin: Preparation and evaluation.

This study was carried out to project a safe nano-drug carrier composed of chitosan and cyanocobalamin (CNCbl) to improve oral delivery of ciprofloxacin hydrochloride (CIP). CIP is classified in class IV of the biopharmaceutical classification system with low solubility and permeabilityA, so it has some problems if given orally. Novel conjugate of low molecular weight chitosan, as a natural biopolymer, and CNCbl was synthesized, and then drug loading and in-vitro drug release were assessed. The loading of CIP was optimized by the Design-Expert software and the central composite design method, and that the optimal drug loading efficiency (57%) was obtained via analysis of variance (ANOVA). In-vitro drug release studies showed controlled release patterns in two various conditions, namely phosphate buffer saline (pH = 7.4) and 0.1 N HCl. Functionalized nano-drug-loaded carrier showed cytotoxicity as much as that of free drug, particle size less than 100 nm as well as positive zeta potential. Due to the beneficial properties of the chitosan-based drug carrier and the suitable features of the CIP-loaded carrier, this chitosan-based nano-drug delivery system can be regarded as an ideal candidate for oral delivery of the CIP as a drug model.

Low-Molecular-Weight Chitosan Attenuates Lipopolysaccharide-Induced Inflammation in IPEC-J2 Cells by Inhibiting the Nuclear Factor-κB Signalling Pathway.

Low-molecular-weight chitosan (LMWC), a product of chitosan deacetylation, possesses anti-inflammatory effects. In the present study, a porcine small intestinal epithelial cell line, IPEC-J2, was used to assess the protective effects of LMWC on lipopolysaccharide (LPS)-induced intestinal epithelial cell injury. IPEC-J2 cells were pretreated with or without LMWC (400 µg/mL) in the presence or absence of LPS (5 µg/mL) for 6 h. LMWC pretreatment increased (p < 0.05) the occludin abundance and decreased (p < 0.05) the tumour necrosis factor-α (TNF-α) production, apoptosis rate and cleaved cysteinyl aspartate-specific protease-3 (caspase-3) and -8 contents in LPS-treated IPEC-J2 cells. Moreover, LMWC pretreatment downregulated (p < 0.05) the expression levels of TNF receptor 1 (TNFR1) and TNFR-associated death domain and decreased (p < 0.05) the nuclear and cytoplasmic abundance of nuclear factor-κB (NF-κB) p65 in LPS-stimulated IPEC-J2 cells. These results suggest that LMWC exerts a mitigation effect on LPS-induced intestinal epithelial cell damage by suppressing TNFR1-mediated apoptosis and decreasing the production of proinflammatory cytokines via the inhibition of NF-κB signalling pathway.