Search Results (91)

Ulcerative colitis (UC) is a chronic inflammatory disorder associated with cytokine imbalance, epigenetic alterations, and metabolic–redox dysfunction. Despite the widespread use of mesalazine (5-ASA), therapeutic limitations remain. Norcantharidin (NCTD), a synthetic cantharidin analogue, may provide multi-target protection against UC. Experimental colitis was induced in male Sprague-Dawley rats by intrarectal administration of 4% acetic acid (AA). Rats received oral NCTD (10 mg/kg), 5-ASA (100 mg/kg), or their combination for 8 days. Disease severity was assessed by disease activity index, body weight, colon length, colon weight/length ratio, and histopathology. Colonic biomarkers were evaluated using ELISA, qRT-PCR, Western blotting, and immunohistochemistry. Fe²⁺ and malondialdehyde (MDA) were measured as indicators of iron accumulation and lipid peroxidation. Molecular docking suggested that NCTD may adopt plausible binding poses within the binding pockets of AMPK, SIRT1, and DNMT1, providing structural support for potential protein–ligand interactions. NCTD significantly ameliorated AA-induced colitis, improving clinical and histological outcomes. These effects were associated with reduced IL-6, TNF-α, DNMT1, Fe²⁺, and MDA levels, restoration of SOCS3, activation of p-AMPK/SIRT1/FOXO3a signaling, and enhancement of Nrf2/HO-1 defenses. Combined NCTD/5-ASA treatment produced greater clinical and histological protection, with differential effects on molecular markers. Docking studies suggested favorable interactions of NCTD with AMPK, SIRT1, and DNMT1. NCTD treatment was associated with protection against experimental colitis, linked to modulation of inflammatory, epigenetic, metabolic, and antioxidant pathways. Full article

Background/Objectives: Manumycin A, a natural polyketide antibiotic isolated from Streptomyces species, has been reported to exhibit anticancer, anti-inflammatory, and immunomodulatory activities through regulation of multiple signaling pathways. However, its therapeutic potential in inflammatory bowel disease (IBD) has not yet been investigated. This study aimed to evaluate the protective effects of Manumycin A in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Experimental colitis was induced in male ICR mice by administration of 3% DSS in drinking water for 7 days. Manumycin A (1, 5, and 10 mg/kg) was administered via intraperitoneal injection, and 5-aminosalicylic acid (100 mg/kg) was used as a positive control. Disease severity was evaluated by body weight changes, disease activity index (DAI), colon length, histopathological analysis, and immunohistochemical assessment of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and IFN-γ. Results: Manumycin A treatment attenuated DSS-induced colitis in a dose-dependent manner. Although body weight changes were modest and did not show statistically significant differences among groups, Manumycin A significantly reduced DAI scores compared with the DSS-treated group. Treatment also alleviated DSS-induced colon shortening and improved histopathological alterations, including epithelial damage, mucosal disruption, and inflammatory cell infiltration. Immunohistochemical analysis showed that Manumycin A reduced the expression of IL-1β, IL-6, TNF-α, and IFN-γ in colon tissues. Conclusions: Manumycin A exerted protective effects against DSS-induced colitis by attenuating inflammatory responses and improving colonic tissue damage. These findings suggest that Manumycin A may have therapeutic potential as a candidate for the treatment of IBD. Full article

Background/Objectives: Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by epithelial injury and excessive inflammatory responses. J2H-1802 is a newly synthesized hybrid molecule designed to combine the pharmacological properties of mycophenolate mofetil and 5-aminosalicylic acid. This study evaluated the protective and anti-inflammatory effects of J2H-1802 in a dextran sulfate sodium (DSS)-induced colitis mouse model and investigated its underlying mechanisms. Methods: Experimental colitis was induced in mice by administration of 2.5% (w/v) DSS for 7 days, followed by oral treatment with J2H-1802. Body weight, stool consistency, fecal bleeding, and disease activity index were assessed. Colon length and spleen weight were measured to evaluate macroscopic damage. Levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues were quantified, and the expression of phosphorylated nuclear factor-κB and cyclooxygenase-2 was analyzed by Western blotting. Results: J2H-1802 alleviated DSS-induced body weight loss, diarrhea, and fecal bleeding, resulting in reduced disease activity index scores. It also prevented colon shortening and attenuated splenomegaly. In addition, J2H-1802 significantly suppressed the elevated levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase in colon tissues. Western blot analysis further showed that J2H-1802 inhibited the DSS-induced upregulation of phosphorylated nuclear factor-κB and cyclooxygenase-2. Conclusions: J2H-1802 protected against DSS-induced colitis by reducing inflammatory responses and inhibiting the nuclear factor-κB/cyclooxygenase-2 signaling pathway. These findings suggest that J2H-1802 functions as a hybrid anti-inflammatory scaffold with in vivo pharmacological activity and may warrant further optimization and investigation in IBD models. Full article

Poor solubility and low permeability remain major obstacles to the oral bioavailability of mesalazine (5-aminosalicylic acid, 5-ASA), a BCS Class IV anti-inflammatory drug used in the treatment of inflammatory bowel diseases. In this study, we report a novel eutectogel (EG) platform based on a natural deep eutectic solvent (NADES) composed of choline chloride and lactic acid (ChCl:LA, 1:10 molar ratio). The NADES significantly enhanced mesalazine solubility, reaching 35 mg/mL, nearly 40-fold higher than in water. The drug-loaded NADES was structured using hydroxyethyl cellulose and Carbomer 140 to obtain a gel matrix, which was subsequently coated with Eudragit^® S100 to provide pH-dependent release and gastro-resistance. Physicochemical characterization was carried out via FT-IR and NMR spectroscopy, polarized optical microscopy (POM), and swelling studies in simulated fluids. In vitro release studies under simulated gastrointestinal conditions revealed minimal drug release at gastric pH (1.2) and a sustained release (>80%) at colonic pH (7.4) over 48 h. These results support the potential of ChCl:LA-based eutectogels as a biocompatible, green, and effective delivery system for the site-specific release of poorly soluble drugs in the colon. Full article

Purpose: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder strongly associated with intestinal microbial dysregulation. Although 5-aminosalicylic acid (5-ASA) is widely used in the clinical management of IBD, its therapeutic efficacy is often limited. To address this, the present study aimed to develop a bifidobacterium-derived extracellular vesicle-based drug delivery system (B-MVs@5-ASA) to enhance the therapeutic outcomes of IBD. Methods: B-MVs were isolated by PEG precipitation and loaded with 5-ASA via sonication to obtain B-MVs@5-ASA. Their morphology, particle size, zeta potential, and encapsulation efficiency were analyzed using TEM, DLS, and UV spectrophotometry. Cellular uptake, cytotoxicity (LDH and NO assays), and anti-inflammatory effects were assessed in RAW 264.7 and Caco-2 cells. A DSS-induced colitis mouse model was established to evaluate therapeutic efficacy. Cytokines (ELISA), colon histopathology (H&E), tight-junction proteins (IF), and gut microbiota composition (16S rRNA sequencing) were systematically analyzed. Results: B-MVs@5-ASA exhibited a particle size of 104.3 ± 2.81 nm and an encapsulation efficiency of 11.14% ± 3.63%. B-MVs@5-ASA exhibited the strongest anti-inflammatory effect in vitro and most effectively alleviated DSS-induced colitis in vivo, outperforming monotherapies in reducing inflammation, tissue damage, and enhancing barrier integrity. B-MVs@5-ASA further promoted goblet cell regeneration and beneficially modulated the gut microbiota by enriching Akkermansia and suppressing Escherichia, thereby restoring microbial homeostasis. Conclusions: B-MVs@5-ASA provides potent anti-inflammatory and mucosal-protective effects by modulating cytokine balance, enhancing epithelial barrier function, and reshaping gut microbiota. These findings highlight probiotic vesicle-based nanoplatforms as a safe and promising strategy for targeted IBD therapy. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

Background/Objectives: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammatory responses, which are primarily driven by the interleukin (IL)-23/Th17 axis. Although current therapies effectively suppress inflammation, their long-term use is often limited by adverse systemic effects, underscoring the need for safe immunomodulatory agents. This study investigated the anti-psoriatic efficacy of J2H-1802, a novel hybrid compound combining mycophenolate mofetil (MMF) and 5-aminosalicylic acid (5-ASA), in an imiquimod (IMQ)-induced psoriasis-like mouse model. Methods: J2H-1802 was orally administered at doses of 125 and 250 mg/kg during IMQ treatment, and its effects were evaluated by conducting clinical assessments, histological analyses, and inflammatory cytokine measurements in the serum and skin tissues. Results: J2H-1802 treatment reduced Psoriasis Area and Severity Index (PASI) scores, skin and ear thickness, and splenomegaly in a dose-dependent manner. Histological examination revealed IMQ-induced epidermal hyperplasia attenuation and dermal collagen organization improvement. In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. Conclusions: J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways. Full article

Background/Objectives: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon that profoundly impacts human health. Conventional pharmacological treatments are associated with serious adverse reactions and toxic side effects. Consequently, the development of natural plant-derived biological agents for UC treatment is an urgent imperative. Methods: Utilising a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis mouse model, with mice receiving low, medium, and high doses of water extract of Tibetan Fritillaria cirrhosa D. Don extract (FCD), alongside a group receiving 5-aminosalicylic acid. The Disease Activity Index (DAI) was calculated, colon length was measured, histological scores were assessed, and histopathological alterations were evaluated. Inflammatory factor were determined by ELISA; mRNA and protein expression in colonic tissue was analysed by RT-qPCR and Western blotting; intestinal barrier-related proteins were examined by immunofluorescence and immunohistochemistry; and gut microbiota composition was assessed by 16S rRNA sequencing. Results: Research has confirmed that FCD alleviates symptoms of DSS-induced colitis in mice, specifically manifested by a slower rate of weight loss, reduced colon shortening, and decreased disease activity index. It has been demonstrated that the process under investigation exerts a beneficial effect on intestinal injury by means of a number of mechanisms. These include increased goblet-cell production, elevated IL-10 levels, and reduced levels of TNF-α, IL-1β, and IL-6. Furthermore, immunofluorescence detection, immunohistochemical analysis, and RT-qPCR results indicate that FCD maintains the integrity of the intestinal mucosal barrier by enhancing the expression of Zonula occludens-1 (ZO-1), occludin, and claudin-1 proteins and their corresponding mRNAs, in addition, FCD can regulate the gut microbiota and promote its diversity. Conclusions: Research indicates that FCD may exert therapeutic effects on ulcerative colitis (UC) by regulating intestinal barrier integrity and modulating the gut microbiota. These findings reinforce the idea that FCD could be used as a natural therapy to improve UC. Full article

Background/Objectives: Cocrystallisation is a well-established path for altering the physicochemical properties and bioavailability of active pharmaceutical ingredients (APIs). A common side effect of anti-tubercular medicines is the depletion of group B vitamin reserves in TB patients. Co-administration of supplements such as pyridoxine (vitamin B₆) during TB therapy may be used to ameliorate the harmful side effects of vitamin B₆ deficiency. Methods: Mechanochemical grinding and solvent evaporation experiments using pyridoxine (PN) with 4-aminosalicylic acid (PAS) and separately with pyrazinecarboxylic acid (PCBA) were conducted. The bulk powder and crystal analysis was performed using FTIR, PXRD, DSC, TGA and SCXRD. Results: The isolation and characterization of two multicomponent salts containing pyridoxine, i.e., PN-PAS·H₂O and PN-PCBA, were completed. Mechanochemistry is an efficient method for the preparation of cocrystals. Conclusions: The drug–vitamin combinations may be useful for the development of new treatment regimens with potentially improved therapeutic outcomes and reduced adverse effects. Full article

Proanthocyanidins (PACs) are a key group of bioactive phytochemicals known to provide health benefits. Most PACs are non-bioavailable polymeric molecules that need to be biotransformed by colonic microbes into simple metabolites to exert their pharmacological effects. In this study, six previously unexamined PAC metabolites from Saccharomyces cerevisiae, 3-aminophenol (3-AMP), 3-aminosalicylic acid, 2,4-dihydroxy-6-methylbenzaldehyde, 4-hydroxyphenylacetamide (4-HPA), 3-phenyllactic acid, and 2,4,6-trihydroxyacetophenone, were tested for their antiadipogenic activity using an insulin-dependent 3T3-L1 preadipocyte differentiation model. Lipid accumulation in differentiating preadipocytes was visualized and measured with the Oil Red O assay. Only 3-AMP and 4-HPA significantly reduced lipid accumulation at a concentration of 25 µM. To understand the cellular mechanisms, protein levels of key regulators of adipogenesis and lipid metabolism were analyzed using Western blotting. 3-AMP and 4-HPA may attenuate lipid accumulation by suppressing de novo lipogenesis, with 3-AMP downregulating the peroxisome proliferator-activated receptor (PPAR)-γ/acetyl-CoA carboxylase (ACC)/fatty acid synthase (FAS) axis and 4-HPA primarily inhibiting ACC/FAS signaling. Molecular docking studies indicated that 3-AMP may downregulate PPAR-γ expression through competitive inhibition of insulin receptors. These preliminary findings suggest that 3-AMP and 4-HPA exhibit potential antiadipogenic effects, highlighting PAC-derived postbiotics as promising nutraceuticals for mitigating obesity risk. Full article

Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), severely affects patients’ quality of life. Sodium butyrate (NaB) has been reported to improve IBD manifestations, although its underlying mechanisms remain incompletely understood. Methods: An IBD mouse model was induced with 3% (w/v) dextran sulfate sodium (DSS). Mice were administered NaB (500 mg/kg, gavage), 5-aminosalicylic acid (5-ASA,150 mg/kg, gavage), or the ferroptosis inhibitor ferrostatin-1 (Fer-1, intraperitoneal injection). Western blotting (WB) and real-time quantitative PCR (RT-qPCR) were performed to evaluate ferroptosis-related molecules and target pathway components. Immunofluorescence staining was used to assess ferroptosis in macrophages preliminarily. Results: NaB alleviated clinical symptoms of IBD in mice, including mitigation of body weight loss, restoration of colon length, reduction in disease activity index (DAI), decreased spleen index, and protection of the intestinal barrier. In addition, compared with the DSS model group, NaB downregulated ACSL4 and upregulated GPX4 and SLC7A11, indicating an inhibitory effect on ferroptosis. WB results showed that SIRT1 expression was enhanced in the DSS + NaB group. In addition, immunofluorescence staining demonstrated that compared with the DSS group, GPX4 expression was increased in macrophages in the DSS + NaB group. Conclusions: NaB alleviates IBD by modulating SIRT1-associated signaling molecules and inhibiting ferroptosis, including inhibiting macrophage ferroptosis. Full article

Background: Inflammatory bowel disease (IBD) is associated with chronic pain and reduced quality of life, even in the absence of active intestinal inflammation. International studies suggest that fibromyalgia (FM), a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, and multiple somatic symptoms, is more prevalent among patients with IBD than among the general population. However, data from Saudi Arabia are limited. Methods: This cross-sectional study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, during July and August of 2024. Patients with biopsy-confirmed IBD were identified from hospital records and contacted by phone to screen for FM using a validated Arabic version of the Fibromyalgia Rapid Screening Tool. Demographic data, comorbidities, medication exposure, IBD characteristics, disease activity, and laboratory parameters were extracted from the medical records and compared between patients with and without FM. Results: Of 274 patients with IBD (mean age 30.9 ± 9.2 years; 56.9% male), 51 (18.6%; 95% CI 14.2–23.7) met criteria for FM. Patients with FM tended to be older than those without and were more likely to have comorbidities, particularly thyroid disorders, as well as low Vitamin D levels. Prior 5-aminosalicylic acid use was also more common among patients with FM. Inflammatory markers, hematological indices, IBD phenotypes, and disease activity were similar between the groups. Conclusions: Saudi patients with IBD often have comorbid FM. Routine FM screening in IBD clinics may help avoid misattributing central pain to active inflammation and unnecessary treatment escalation. Full article

The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2a–f, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article

The formation of interfacial charge transfer (ICT) complexes between phenolic ligands and metal oxide surfaces enables surface functionalization strategies with potential applications in catalysis and bioconjugation. In this study, magnetite (Fe₃O₄) nanoparticles were modified with two phenolic ligands, 5-aminosalicylic acid (5ASA) and caffeic acid (CA), to generate ICT complexes capable of covalent or non-covalent enzyme immobilization, respectively. The modified nanomaterials were structurally characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). Horseradish peroxidase (HRP) was immobilized on these functionalized supports using varying nanoparticle amounts (10–30 mg) and initial enzyme concentrations (25–250 µg mL⁻¹). Catalytic activity was evaluated using pyrogallol oxidation assays. The Fe₃O₄/5ASA–HRP system exhibited a maximum activity of 2.5 U per 20 mg of support (approximately 125 U g⁻¹), whereas Fe₃O₄/CA showed minimal activity under the same conditions. Enzyme loading studies confirmed that 5ASA-enabled covalent attachment resulted in significantly higher immobilization efficiency (up to 1068 mg g⁻¹) compared to the CA system. Reusability tests demonstrated that the Fe₃O₄/5ASA system retained high absolute catalytic activity during the initial reaction cycles and consistently outperformed the non-covalently immobilized Fe₃O₄/CA system upon repeated reuse. The magnetic properties of Fe₃O₄ allowed rapid recovery of the biocatalysts using an external magnetic field. These results highlight the effectiveness of ICT-based functionalization for enzyme immobilization, positioning Fe₃O₄/5ASA as a promising platform for robust and reusable biocatalysts in environmental and industrial applications. Full article

Gallium-based liquid metals have been extensively studied in the field of biomedical engineering, including applications in tumor and inflammatory disease therapy, as well as targeted drug delivery. Among these, leveraging the photothermal effect of gallium liquid metals enables effective treatment of heat-sensitive cells in tumor regions and enhances the diffusion capability of liquid metal microdroplets. However, research on the active treatment of ulcerative colitis (UC) using photothermal therapy with liquid metals remains unexplored. This study focuses on constructing an active composite colloidal motor based on gallium indium liquid metal alloy, using liquid metal microdroplets as the core. Through layer-by-layer assembly of polyelectrolytes, a liquid metal active droplet loaded with the drug mesalazine (5-aminosalicylic acid), named as LMAD-A was developed. Under asymmetric light fields generated by NIR-II light source irradiation, LMAD-A exhibits autonomous locomotion, achieving an effective diffusion coefficient more than 800 times greater than that of Brownian motion in liquid metal microdroplets of similar size. Furthermore, LMAD-A demonstrates phototactic behavior, moving toward the NIR light source autonomously. Through in vitro and in vivo experiments in mice, it was verified that LMAD-A can aggregate, deform, and fuse in the mouse colon under photothermal effects, leading to enhanced release of the loaded drug. In simulated treatments, LMAD-A significantly alleviated DSS-induced colitis in mice, confirming the targeted therapeutic capability of active liquid metal microdroplets as an active therapeutic agent in UC-affected regions. Full article