CARRAGEENAN

Carrageenans are versatile sulfated marine galactans that possess attractive modification-dependent bulk properties, making them prime candidates for various cosmetic, drug delivery, and food-related applications. The structural diversity and intrinsic complexity of carrageenans hamper access to homogeneous polysaccharides, limiting the development of many carrageenan-based applications. We devised a synthetic strategy for the acquisition of a panel of γ-carrageenan-derived oligosaccharides with varying sulfation profiles and chain length. To that end, we synthesized a set of specialized building blocks with an elaborate multilevel protecting group hierarchy, tailor-made to specifically accommodate the structural complexity of carrageenans. In doing so, we uncovered interdependent protecting group and reactivity constraints, which we resolved strategically to adapt the synthetic route across the panel of carrageenans and minimize trade-offs. Assembly of di-, tri-, and tetrasaccharides with precise control over monomer connectivity and regiodefined sulfation on a conjugation-ready linker showcased the first total synthesis of homogeneous carrageenan oligogalactans. We demonstrated that the application of the curated panel enabled elucidation of the effect of γ-carrageenan molecular features on IL-8 binding preferences via electrochemical sensing and surface analyses.

Cynoglossum clandestinum Desf. (C. clandestinum Desf.) is a wild Moroccan medicinal species traditionally used for wounds, burns, microbial infections, and inflammatory skin disorders. This work aimed to characterize the phytochemical composition of the ethanolic leaf extract of C. clandestinum Desf. and to evaluate its antioxidant, anti-inflammatory, and antidepressant-like activities using in vitro, in vivo, and in silico approaches. Leaves were macerated in absolute ethanol to obtain a reproducible ethanol-soluble fraction. Total phenolic and flavonoid contents were determined, and major compounds were identified by HPLC-DAD. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Anti-inflammatory activity was evaluated in the carrageenan-induced paw edema model, and antidepressant-like activity was assessed in the forced swimming test in rats. Major identified compounds were further examined by ADMET prediction and molecular docking. The extract contained 51.25 ± 1.06 mg GAE/g of total phenolics and 41.14 ± 1.81 mg QE/g of total flavonoids. HPLC-DAD identified six major phenolics, with quercetin-3-glucoside (12.08%) and epicatechin (10.17%) as the most abundant compounds. The extract showed strong antioxidant activity (DPPH IC 50  = 0.290 ± 0.03 μg/mL; TAC = 295.83 ± 6.71 mg AAE/g), dose-dependent anti-inflammatory activity (63.64% edema inhibition at 400 mg/kg at T6), and a significant reduction in immobility time in the forced swimming test. Docking suggested quercetin-3-glucoside as the best xanthine oxidase binder, whereas quercetin showed the highest affinity for COX-2 and MAO-A. The ethanolic leaf extract of C. clandestinum Desf. is rich in bioactive phenolics and shows promising antioxidant, anti-inflammatory, and antidepressant-like effects. Quercetin-3-glucoside appears to be the main antioxidant-oriented lead, whereas quercetin is the most promising anti-inflammatory and antidepressant-oriented lead. Further studies on isolated compounds, toxicity, and pharmacokinetics are required.

Precise, synchronous monitoring of cervical kinematics and muscle electrophysiology is critical for early intervention in neck pain, yet remains constrained by the unimodal functionality, limited biocompatibility, and restricted accuracy of existing wearable technologies. To overcome these limitations, we developed an imperceptible multimodal, hydrogel-based electronic skin based on tannic acid (TA)-modified polyacrylamide-carrageenan (PCT) hydrogel, which simultaneously enables high-fidelity strain sensing and surface electromyography (sEMG) acquisition with optimized conductivity (1.03 S/m), stretchability (>300%), and tissue adhesion (12.1 kPa). TA doping (100 mg/mL) achieves balanced adhesion-conductivity-mechanical robustness trade-offs. Strain sensing exhibits gold-standard correlation with 3D motion capture ( r = 0.9904) and high linearity at cervical-relevant strains (0-30%: GF = 1.15, R 2 > 0.999). The first multimodal biosafety validation was conducted via fNIRS-based cortical pain mapping, confirming zero neural activation during wear. A cervical spine strain sensor and a trapezius sEMG array interface were integrated with flexible electronics for real-time wireless fatigue/posture alerts. This platform enables proactive neck pain management through precision biomechanical telemonitoring, advancing human-machine interfaces for tele-rehabilitation.

This study evaluated the immunomodulatory role of somatostatin-6 (SST6) in gilthead seabream (Sparus aurata) using a validated inflammation model induced by λ-carrageenan and a comprehensive panel of serum and skin mucus biomarkers. SST6 was administered at 1 nM and 2 nM, and its effects were assessed in these matrices. In fish injected with SST6 alone, serum alternative complement activity increased at both concentrations. In skin mucus, λ-carrageenan reduced peroxidase, esterase, and protease activities, whereas SST6 administration was associated with lower non-Ig protein levels and reduced peroxidase, esterase, and protease activities. When combined with λ-carrageenan, SST6 at 1 nM increased serum immunoglobulin levels and α2-globulins in the proteinogram fractions, while further decreasing the oxidative and proteolytic activities in skin mucus. Correlation analysis revealed the coordinated regulation of key mucosal enzymes, reinforcing the functional integration of local immune responses. These results indicate that SST6 is able to modulate systemic and mucosal humoral biomarkers. Furthermore, this study provides the first evidence of complement activation by SST6 in fish and highlights the value of integrating biomarker-based tools to monitor immunophysiological responses and test bioactive compounds in aquaculture research.

Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is often limited by poor skin permeability and short duration of action. Solid lipid nanoparticles (SLNs) offer a promising carrier system to enhance dermal delivery and sustain local therapeutic effects. This study aimed to formulate and optimize ketoprofen (KP)-loaded SLNs to improve its efficacy in topical inflammatory conditions. A mixture design was applied for modeling and optimization of formulation variables. SLNs were prepared using hot melting and solvent evaporation techniques and characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and drug release. Pharmacodynamic evaluation was conducted using a carrageenan-induced paw edema model in rats, compared with a marketed formulation (FASTUM gel 2.5%). The optimized SLNs showed a particle size of 51.9±4.55 nm, PDI of 0.398±0.02, and zeta potential of -14.2±0.61 mV, indicating acceptable stability. The optimized formulation significantly reduced paw edema by 57.65% and decreased PGE2 and TNF-α levels by 55.6% and 58.4%, respectively (P < 0.05). Additionally, the SLN gel exhibited enhanced bioadhesion (+81%) and doubled permeation flux compared to the pure drug gel. These findings support SLNs as an effective platform for topical NSAID delivery.

Background/Objectives: Seasonal waves of respiratory viruses-including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)-continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry ( Sambucus nigra L.) fruit extract (ElderCraft ® ; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAV PR8 , human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness.

Transposable elements are major components of teleost genomes. However, their transcriptional regulation during inflammatory responses has not been investigated in vivo in teleosts. In this study, we used a λ-carrageenan model of sterile inflammation in gilthead seabream and analysed skin and brain RNA-seq data using a workflow that jointly quantified transcripts derived from TE families and host genes. This study aimed to determine whether λ-carrageenan alters TE family transcription as part of an integrated response to inflammation. Under basal conditions, we detected widespread transcription from Class I and Class II TE families in each tissue. Following λ-carrageenan injection, differential expression analysis identified a limited but consistent TE response. In skin, 19 TE families and 1035 genes were differentially expressed, whereas in the brain, 15 TE families and 874 genes changed expression. When grouping TEs at the class level, the skin response was characterised by a predominance of induced Class II elements, whereas the brain response was characterised by repressed Class I TE families. Differentially expressed TE families were distributed across all the chromosomes and frequently occurred in genomic regions that also contained differentially expressed genes. Functional enrichment analysis suggested that genes near the regulated TEs were mainly related to metabolic pathways in skin and adaptive immune functions in brain. These findings suggest that inflammation could be associated with differential transcription of a subset of TE families in these tissues. These results a new perspective on the relationship between TEs and the immune system of fish of interest in aquaculture.

Kappa-carrageenan (κ-CRG) forms thermo-reversible physical hydrogels via a coil-helix transition and helix bundling, but its sulfate-driven electrostatic repulsion limits mechanical robustness and control over aqueous disintegration. Here, we show that plant-derived polyphenols reprogram κ-CRG gel through sulfate-directed binding in a structure-dependent manner. Tannic acid (TA) selectively engages κ-CRG sulfate groups, yielding transparent gels and a >5-fold increase in storage modulus, whereas the same TA triggers turbidity and precipitation in sulfate-free agarose, supporting sulfate-mediated specificity. Using monomeric pyrogallol as a galloyl analogue, we demonstrate that monovalent interactions partially reinforce κ-CRG but lack cooperative stabilization. Intervention timing further separates mechanism. Pyrogallol produces pathway-dependent mechanics and gelation temperature, while TA is stage-insensitive, consistent with multivalent network annealing. In simulated gastric/intestinal fluids, pyrogallol/κ-CRG gels retain morphology longer, whereas TA/κ-CRG ones disintegrate rapidly yet exhibit strong adhesion to rough substrates and human skin. These findings provide a fully food-grade route to tune κ-CRG mechanics, thermal behavior, adhesion and programmed disintegration.

This study aimed to fabricate and characterize a polymeric matrix-type transdermal patch containing Mitragyna speciosa ethanolic extract (MSE) using an Eudragit RL100/polyvinylpyrrolidone (ERL/PVP) matrix. Eight different MSE polymeric matrices with varying ERL/PVP ratios, solvent-type permeation enhancers, and MSE loadings were successfully prepared using the solvent casting technique. All polymeric matrices had average thickness of 272.5-316.0 μm with mitragynine content of 198.45-280.86 µg/cm². ATR-FTIR indicated a lack of intermolecular interactions between MSE and ERL or PVP. Mitragynine release followed a square root of time dependence, with a rate of 12.74-17.72 µg/cm 2 /h 1/2 , regulated by a diffusion-controlled process. Ex vivo skin absorption using porcine ear skin showed that mitragynine permeated with initial permeation flux of 1.55-2.84 µg/cm 2 /h. Inclusion of 10% diethylene glycol monoethyl ether enhanced mitragynine skin deposition and permeation efficiency, yielding total skin absorption of 30.88% of the applied dose at 24 h. An anti-inflammatory study using carrageenan-induced paw edema in Wistar rats demonstrated the efficacy of MSE patch administration through systemic effects (dorsal region) and local effects (paw area). Expression of pro-inflammatory genes (IL-6, iNOS, and TNF-α) in the paw tissue treated with the MSE patch was significantly reduced compared to that with the placebo. In vivo skin absorption demonstrated that MSE patches delivered mitragynine systemically at a low concentration (< 0.48 µg/mL), while remaining safe and not inducing skin irritation. The information in this study highlights the potential of polymeric matrix as a simple, conventional, noninvasive alternative transdermal carrier for MSE to alleviate local inflammation and pain associated with inflammatory conditions.

Alpha-tocopherol (vitamin E) is a fat-soluble antioxidant with neuroprotective properties. There is a gap in research regarding the anti-nociceptive and anti-inflammatory effects of alpha-tocopherol in different tests of nociception as well as its signaling pathways. Therefore, this study aimed to assess the anti-nociceptive and anti-inflammatory effects of alpha-tocopherol in vivo and examine the potential involvement of transient receptor potential vanilloid 1 (TRPV1) and downstream kinase pathways, particularly protein kinases protein kinase A (PKA) and protein kinase C (PKC). Male Swiss albino mice were used in acetic acid-induced writhing, immersion tail-flick, and hot-plate tests for nociception while male Wistar rats were used in carrageenan-induced paw edema assay for inflammation. Alpha-tocopherol (50 mg/kg, i.p.), alone or in combination with TRPV1 antagonist (capsazepine) or PKC/PKA inhibitors (Go 6976, H89, respectively) was administered, followed by conducting the behavioral tests. TRPV1 expression in brain and skin tissues was examined using immunohistochemistry. Alpha-tocopherol significantly reduced writhing responses and extended heat latency in thermal tests. The TRPV1 was involved in the hot-plate and immersion tail-flick assays, while PKC and PKA pathways were implicated in the supraspinal analgesic effect (the hot plate test). Alpha-tocopherol (20 μg) did not exert any significant anti-inflammatory effect in the carrageenan model. Intense TRPV1 immunolabeling was observed in the alpha-tocopherol/ carrageenan condition, particularly in the skin. Alpha-tocopherol possesses a strong anti-nociceptive effect through TRPV1 modulation via PKC/PKA-dependent mechanisms. These findings suggest that alpha-tocopherol can be used as an adjuvant in multimodal pain management protocols.

This study aims to evaluate the antioxidant and anti-inflammatory potential of dichloromethanic, methanolic and hydroalcoholic extracts of seventeen different selected Balkan medicinal herbs with ethnopharmacological interest, with the goal of identifying the most bioactive candidates for further investigation of their therapeutic efficacy in human diseases. A total of fifty-four extracts were initially screened; due to the high sample number, only the most active samples were advanced to subsequent assays in order to identify bioactive candidates with potential therapeutic efficacy in human diseases. The methanolic extract of Cotinus coggygria showed the highest radical scavenging activity (DPPH: 96.4% inhibition), the hydroalcoholic extract of Hypericum empetrifolium exhibited the most potent iron chelation (IC 50 : 5.0 μg/mL) and the methanolic extract of Sedum sediforme presented the best anti-inflammatory activity in in vitro assays (LOX IC 50 : 39.4 μg/mL, COX-1 inhibition: 93.1% and COX-2 inhibition: 94.0%). Furthermore, significant inhibition of tyrosinase and collagenase was observed for the methanolic extract of Cistus creticus (94.2% tyrosinase inhibition, 86.8% collagenase inhibition) and the methanolic extract of Cotinus coggygria (83.1% tyrosinase inhibition, 96.1% collagenase inhibition). In vivo, five promising plant extracts were selected and evaluated for their anti-inflammatory activity using a carrageenan-induced paw edema model in female C57BL/6 mice. The study aimed to assess the in vivo anti-inflammatory potential of these extracts under acute inflammatory conditions. The methanolic extract of Cotinus coggygria proved the most active, significantly reducing paw edema by 34% compared to the non-treated control, indicating a pronounced anti-inflammatory effect and supporting its potential as a source of bioactive compounds with therapeutic relevance. The results of this study indicate that several selected herbal extracts exhibit notable pharmacological activities. Given their antioxidant, anti-inflammatory, and inhibitory properties against enzymes related to skin function, these extracts warrant further in vivo and (pre)clinical investigation for potential use in cosmetic and pharmaceutical products targeting skin disorders associated with inflammation and oxidative stress.

Pothos scandens , belonging to the Araceae family, locally known as "batilata," is traditionally used for treating various chronic diseases in folk medicine, such as epilepsy, seizures, convulsions, wounds, snakebites, skin issues, asthma, muscle problems, and diarrhea. This research examined the anxiolytic, antidepressant, analgesic, and anti-inflammatory potentials of the acetone extract of P. scandens whole plant (APS) on in vivo mice and rat models. The elevated plus maze (EPM) and hole board tests (HBTs) were carried out to assess the anxiolytic effects, while antidepressant activity with forced swimming test (FST) and tail suspension test (TST) and the acetic acid-induced writhing and formalin-induced licking tests on Swiss albino mice were used to evaluate the analgesic activity, and the carrageenan-induced rat paw edema model was applied for anti-inflammatory effect. APS at 400 mg/kg exhibited significant anxiolytic ( p < 0.001) and antidepressant ( p < 0.01) effects. This study also demonstrated that APS has dose-dependent and significant analgesic effects for acetic acid-induced writhing ( p < 0.05) and formalin-induced licking tests ( p < 0.01), respectively, as well as anti-inflammatory ( p < 0.001) activities compared to the standard diclofenac sodium. Furthermore, 11 compounds were detected in the extract through GC-MS. These phytochemicals exhibited significant binding affinities, excellent pharmacokinetics, and a safe toxicological profile, as reported by in silico molecular docking and ADMET analysis. The outcomes of this study confirmed that the presence of bioactive compounds in APS offers it considerable potential as a multimodal therapeutic substance with neuropharmacological, analgesic, and anti-inflammatory properties.