Earlier breast-cancer studies have associated it with cell-cycle arrest, apoptosis, inhibition of invasion and angiogenesis, and reduced expression of matrix metalloproteinases. The investigators selected zein, a plant protein derived from maize, as the nanoparticle core because it is biodegradable, inexpensive, and able to encapsulate hydrophobic compounds without toxic chemical crosslinkers. Fucoidan, a sulfated polysaccharide obtained from marine algae, was attached to the particle surface through electrostatic attraction between its negatively charged groups and positively charged zein.

Particles were assembled by antisolvent precipitation: a zein and psoralen mixture in dimethyl sulfoxide was added dropwise to an aqueous fucoidan solution under rapid stirring. Centrifugation then removed excess drug. Transmission electron microscopy showed that the resulting particles were nearly spherical.

Their hydrodynamic diameter was 129.23 ± 0.18 nanometers, compared with 92.13 ± 0.74 nanometers for uncoated PSO-Z nanoparticles. Coating reversed the particles’ zeta potential from positive to negative, with the fucoidan-coated formulation measuring −24.8 ± 0.02 millivolts. High-performance liquid chromatography determined an encapsulation efficiency of 73.13 ± 0.98% and a drug-loading capacity of 5.40 ± 0.35%.

Several analytical methods supported the presence of psoralen and the successful attachment of fucoidan. Fourier-transform infrared spectroscopy showed shifts in bands associated with sulfate-related groups, hydrogen bonding, and interactions between the polysaccharide and zein. X-ray photoelectron spectroscopy detected a distinct sulfur 2p signal at 168.52 electronvolts after coating, while shifts in oxygen and nitrogen signals were consistent with hydrogen bonding and electrostatic attraction.

X-ray diffraction and differential scanning calorimetry showed neither the characteristic crystalline peaks nor the 135–145 degrees Celsius melting peak of free psoralen, supporting an amorphous or molecularly dispersed state in the zein matrix. Circular dichroism and infrared evidence indicated changes in zein’s secondary structure, including diminished alpha-helical signals and increased beta-sheet-rich aggregation interpreted by the authors as consequences of hydrophobic interactions and pi–pi stacking. The coating also altered drug-release behavior across pH conditions.

In dialysis experiments performed at 37 degrees Celsius, cumulative psoralen release after 48 hours was 92.4 ± 3.3% at pH 5.5, 52.4 ± 1.0% at pH 6.5, and 39.1 ± 1.3% at pH 7.4. The authors proposed that acidity weakened electrostatic interactions between fucoidan and zein, loosening the combined barrier around the drug. Incubation in 50% serum at 37 degrees Celsius produced little change in the particle size or polydispersity index of PSO-Z/F nanoparticles over seven days.

Uncoated PSO-Z particles initially increased to approximately 800 nanometers before gradually declining. Coated particles released less than 10% of their psoralen during seven days in both tested storage conditions. In red-blood-cell assays using blood from healthy female BALB/c mice, hemolysis rates for blank Z/F particles, uncoated PSO-Z particles, and coated PSO-Z/F particles were each below 3%.

In 4T1 murine breast-cancer cells, all drug treatments were evaluated at an equivalent psoralen concentration of 105 micrograms per milliliter for 48 hours. A CCK-8 assay showed greater cytotoxicity for the nanoparticle formulations than for free psoralen, with the fucoidan-coated particles producing the strongest suppression of cell viability; the blank Z/F carrier had negligible cytotoxicity. Fluorescence microscopy and flow cytometry found that uptake of FITC-labeled PSO-Z/F particles was 1.6-fold higher than uptake of corresponding uncoated particles, a statistically significant difference.

The results associate the fucoidan shell with improved cellular internalization, but the experiments did not resolve whether the increase arose from tumor-associated binding, altered surface properties, or another uptake mechanism. The coated particles also reduced several measured behaviors associated with movement of 4T1 cells. In the scratch-wound assay, the grayscale-derived wound closure rate was 29.13 ± 3.33% in untreated cultures, 18.34 ± 2.52% after free psoralen, and 5.02 ± 2.86% after PSO-Z/F treatment; the coated-particle result was significantly lower than both comparisons.

In transwell assays, migrated cells declined from 220 ± 33 with free psoralen to 146 ± 20 with PSO-Z/F nanoparticles, while invasive cells fell from 144 ± 21 to 90 ± 8. Annexin V-FITC and propidium iodide staining measured total apoptosis at 6.45% in control cells, 9.86% with blank carrier particles, and 17.98% with PSO-Z/F nanoparticles, with most of the drug-associated increase occurring in late apoptotic cells. These laboratory measurements concern proliferation, migration, invasion, and cell death in one cell line and do not establish that the formulation prevents metastasis in patients.

Near-infrared fluorescence imaging in 4T1 tumor-bearing mice indicated differences in distribution and retention between coated and uncoated particles. Both formulations produced signals in tumors, liver, and lung. Tumor fluorescence from PSO-Cy5.5@Z/F nanoparticles rose to a peak at 24 hours and remained detectable at 96 hours, whereas fluorescence from uncoated PSO-Cy5.5@Z particles peaked at 12 hours and was lower throughout the observation period.

The researchers described the pattern as consistent with enhanced tumor accumulation and retention under the experimental conditions. They also noted that strong liver fluorescence may reflect uptake by the mononuclear phagocyte system, while lung signals could represent distribution or retention in pulmonary microvasculature; neither mechanism was tested directly. The imaging results alone did not establish active tumor targeting or prolonged systemic circulation.

For the therapeutic experiment, mice with 4T1 tumors received intravenous PBS, paclitaxel at 3 milligrams per kilogram, free psoralen at 3 milligrams per kilogram, blank Z/F nanoparticles, or PSO-Z/F nanoparticles at a psoralen-equivalent dose of 3 milligrams per kilogram. Treatments were administered every three days for 14 days, with five animals per group. The researchers reported random allocation and allocation concealment.

PSO-Z/F nanoparticles inhibited tumor growth significantly more than PBS and free psoralen, and treated mice had the smallest final tumor volumes and weights among the groups. The blank carrier did not significantly change tumor growth relative to PBS. TUNEL staining showed prominent apoptotic signals in tumors from the coated-particle group, stronger than those in the free-psoralen group, while control tumors had no evident TUNEL-positive signal.

No significant body-weight loss occurred during treatment. Histological examinations of the heart, liver, spleen, lungs, and kidneys found no apparent treatment-related inflammatory-cell infiltration, hemorrhage, necrosis, cellular degeneration, or disruption of tissue architecture. These observations, together with the body-weight and red-blood-cell results, support preliminary tolerability under the tested conditions but are not a comprehensive safety assessment.

The antitumor experiment used a single murine 4T1 tumor model, small groups, and a short treatment period, while metastasis was evaluated in vitro rather than in a dedicated metastatic model. The authors also identified incomplete control groups as a limitation.

Subject of Research: Fucoidan-coated zein nanoparticles for delivering psoralen in preclinical breast-cancer models

Article Title: Sulfated polysaccharide-coated protein nanoparticles for enhanced delivery of psoralen in breast cancer therapy

Article References: Guo, H., Liang, J., Huang, H., Zhang, Z., Huang, X., Sun, Z., & Huang, Y. (2026). Sulfated polysaccharide-coated protein nanoparticles for enhanced delivery of psoralen in breast cancer therapy. Frontiers in Pharmacology, 17, Article 1888270. https://doi.org/10.3389/fphar.2026.1888270

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1888270

Keywords: breast cancer, psoralen, fucoidan, zein nanoparticles, drug delivery, nanomedicine, 4T1 cells, tumor accumulation, cellular uptake, preclinical research, Sulfated, polysaccharide-coated

The research team, led by Omar Arroyo-Xochihua, focused on RAW 264.7 macrophages, a murine cell line that has become the workhorse of inflammation research worldwide. These cells were stimulated with lipopolysaccharide, or LPS, a molecule found in the outer membrane of Gram-negative bacteria that reliably triggers a full-blown inflammatory response. Once the macrophages were activated in this way, the scientists treated them with an ethanol-water extract of E. menziesii and with four fractions separated by polarity: hexane, dichloromethane, ethyl acetate, and a residual aqueous fraction. The goal was to see whether any of these preparations could rein in the cellular storm that LPS ignites.

Before any biological testing could begin, the team needed to know what was actually inside the seaweed. Using proton nuclear magnetic resonance spectroscopy, or 1H-NMR, they generated chemical fingerprints of the crude extract and each fraction. The spectra revealed a rich assortment of proton signals spanning alkyl, hydroxyl, amino, alkene, and aromatic regions. Three regions stood out. Signals between 1.10 and 1.25 parts per million corresponded to the methyl groups of fucoidan, a sulfated polysaccharide abundant in brown seaweed cell walls. Signals between 5.0 and 5.8 parts per million marked the anomeric protons of fucoidan’s sugar rings. And a dense cluster between 3 and 5 parts per million pointed to mannitol, a sugar alcohol that brown algae use as a carbon transport molecule and osmolyte.

Safety came first. Using the MTT assay, which measures mitochondrial activity as a proxy for cell health, the researchers exposed macrophages to concentrations ranging from 12.5 to 1000 micrograms per milliliter over 24 and 48 hours. The extract and all fractions kept cell viability at or above 90 percent across the tested range, and the calculated half-maximal inhibitory concentration exceeded 1000 micrograms per milliliter at both time points. Only the highest concentration of the crude extract showed any hint of toxicity at 48 hours, and it was excluded from further experiments. Hydrogen peroxide, used as a positive cytotoxicity control, killed cells as expected, confirming the assay was working. The result establishes that the seaweed preparations are safe for cellular experimentation at the doses that produced biological effects.

With safety established, the team turned to a scratch assay, a simple but informative test of cell migration. A sterile pipette tip drags a wound-like gap through a confluent monolayer of macrophages, and researchers then measure how quickly cells migrate in to close the gap. LPS alone impaired migration, leaving the scratched area largely open at 48 hours. Treatment with the crude ethanol-water extract significantly reversed this effect, reducing the free scratched area by up to 40 percent at 24 hours compared with the LPS-stimulated control. The aqueous fraction performed even better, showing significant scratch closure at both 24 and 48 hours, with reductions approaching 10 percent of the original wound area remaining at the later time point. Curcumin and indomethacin, included as natural and pharmacological controls, also promoted closure, but the seaweed treatments held their own against these benchmarks.

The most technically ambitious part of the study came next. Rather than guessing which compounds were responsible, the researchers applied multivariate data analysis, specifically Orthogonal Partial Least-Squares modeling, to correlate the NMR spectra with the scratch closure measurements. The resulting statistical model was strikingly robust, with explained variance values above 0.95 and predictive Q-squared values of 0.97 and 0.93 at 24 and 48 hours respectively, and cross-validation confirmed the model was not overfitted. The contribution plots revealed that proton signals in the 0.6 to 3 parts per million region were the main contributors to the anti-migratory rescue effect. This region encompasses the methyl groups of fucoidan and the alcohol protons of mannitol, providing chemometric evidence that these two abundant seaweed metabolites are the likely active principles.

Phagocytosis, the process by which macrophages engulf debris and pathogens, told a more nuanced story. Measured with a neutral red uptake assay, phagocytic activity surged in LPS-stimulated cells, as expected. The crude extract brought this activity back down below the levels seen in unstimulated controls, suggesting a normalizing rather than suppressive effect. Interestingly, the dichloromethane, ethyl acetate, and aqueous fractions each increased phagocytic activity above unstimulated baseline levels, hinting that different components of the seaweed may push macrophage behavior in different directions depending on the chemical context. The hexane fraction showed no significant effect either way.

The clearest anti-inflammatory signal emerged from the cytokine measurements. Using reverse transcription quantitative PCR and enzyme-linked immunosorbent assays, the team quantified both messenger RNA and secreted protein levels of interleukin-1 beta and interleukin-6, two pro-inflammatory cytokines central to the M1 macrophage phenotype that LPS induces. The crude extract cut IL-1 beta mRNA expression to less than half of the LPS-stimulated level and kept IL-6 fold change below 3, with corresponding reductions at the protein level that matched the effect of indomethacin. The aqueous fraction also significantly reduced both cytokines, though its protein-level effects were less complete. Notably, neither curcumin nor indomethacin achieved significant reductions in cytokine gene expression in this system, making the seaweed’s performance at the transcript level particularly noteworthy.

The mechanistic story fits with a growing body of literature on sulfated polysaccharides. Fucoidan’s negatively charged sulfate groups are thought to interact electrostatically with inflammatory mediators, and studies of fucoidan from related brown seaweeds have shown that it can block the NF-kappa B signaling pathway, a master transcriptional switch for inflammatory genes. Mannitol, meanwhile, has been shown to reduce markers of M1-like macrophage and microglial activation in animal models of neuroinflammation, possibly through osmotic effects that alter immune cell behavior. The authors caution that the compounds in a crude extract may act synergistically or even antagonistically, and that a single murine cell line in a monolayer cannot capture the full complexity of inflammation in a living organism. Future work, they suggest, should test human cell lines, explore nitric oxide and other inflammatory mediators, and pursue full metabolomic profiling.

Still, the implications are considerable. Non-steroidal anti-inflammatory drugs remain among the most widely consumed medications on Earth, and their long-term use is linked to gastrointestinal damage, ulcers, and elevated cardiovascular risk. Marine organisms remain a strikingly underexplored source of alternatives; between 1981 and 2019, more than fifty natural products and derivatives for treating inflammation were approved, yet marine species account for only a small fraction of the research effort. Egregia menziesii, with its limited range from Alaska to Baja California and its documented safety across multiple cell types and whole-organism models, now joins the shortlist of seaweeds with credible immunomodulatory credentials. If the fucoidan and mannitol hypothesis holds up in more complex systems, the feather boa kelp swaying in the Pacific surf could one day contribute to medicines that quiet inflammation without the collateral damage of current drugs.

Subject of Research: Anti-inflammatory activity and chemical profiling of Egregia menziesii extracts in LPS-activated macrophages

Article Title: Chemical profiling of Egregia menziesii and anti-inflammatory potential in LPS-activated RAW 264.7 macrophages

Article References: Arroyo-Xochihua, O., Sánchez-Medina, A., López-Franco, Ó., Olivares-Bañuelos, T. N., & Zepeda, R. C. (2026). Chemical profiling of Egregia menziesii and anti-inflammatory potential in LPS-activated RAW 264.7 macrophages. Molecular Biology Reports, 53(1), Article 1529. https://doi.org/10.1007/s11033-026-12685-y

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12685-y

Keywords: Egregia menziesii, brown seaweed, fucoidan, mannitol, macrophages, inflammation, cytokines, 1H-NMR, chemometrics, RAW 264.7, sulfated polysaccharides, natural products

The original paper, published on 11 January 2021, examined the antitumor effect and molecular mechanism of fucoidan in non-small cell lung cancer, the most common category of lung malignancy, which includes adenocarcinomas and squamous cell carcinomas. Fucoidan has attracted sustained attention in the complementary medicine literature because it is a readily available seaweed extract with reported immunomodulatory and anti-proliferative properties, and laboratory studies have repeatedly suggested that it can interfere with signaling pathways that drive cancer cell growth. The retracted study focused on two widely used lung cancer cell lines, A549 and H1650, and reported effects on proteins involved in cell-cycle control and growth signaling.

According to the retraction notice, the problems centered on Figure 2 of the original article, which presented western blot data, a technique in which proteins separated by size are transferred to a membrane and detected with antibodies to reveal whether a target protein is more or less abundant under different experimental conditions. In cancer mechanism studies, western blots are often the decisive evidence that a treatment changed the level of a specific protein, so the authenticity of each band carries substantial weight. The editors identified multiple similarities that should not exist between bands that were supposed to represent different proteins in different experiments.

Specifically, the notice describes a similarity between the Cyclin D1 band in A549 cells shown in Figure 2A and the pm-TOR band in A549 cells shown in Figure 2B. Cyclin D1 is a cell-cycle protein that pushes cells through the G1 phase and is frequently overactive in cancer, while pm-TOR refers to phosphorylated mTOR, the activated form of a central growth-regulating kinase that integrates nutrient and growth-factor signals. A single image cannot legitimately serve as the detection signal for two different proteins probed in two different assays, because each western blot experiment involves separate gel electrophoresis, transfer, antibody incubation, and chemiluminescent detection steps that produce distinct banding patterns.

The editors also documented similarities between panels that were supposed to show results from the two different cell lines treated with the same fucoidan concentrations. The upper part of the A549 panel treated with fucoidan at 10 milligrams per milliliter was found to be similar to the lower part of the H1650 panel at the same concentration, and the lower part of the A549 panel at 16 milligrams per milliliter was similar to the upper part of the corresponding H1650 panel. A549 and H1650 cells are biologically distinct models, derived from different patients and carrying different genetic backgrounds, so their protein expression patterns under identical treatment conditions would be expected to differ. Overlapping image content between such panels suggests that the same underlying image material was reused to represent separate experiments.

The retraction notice records the authors’ responses, which were divided. Authors Xiaohan Chen and Haijun Lu agreed with the retraction, while authors Li Sun, Xiaojuan Wei, Ye Tan, Zhanyi Sun, and Jinju Jiang did not respond to correspondence from the publisher about the retraction. The absence of a coordinated institutional response left the editors with no credible explanation for the duplicated image content, and the notice states plainly that the editors therefore lost confidence in the data and conclusions of the article. The retraction note itself was published on 19 October 2026 as volume 26, article number 310 of the journal, more than five years after the original publication.

The author list of the original paper also reflects a collaboration that bridged clinical and commercial interests. Several authors were affiliated with the Department of Oncology at the Affiliated Hospital of Qingdao University and with Heze Municipal Hospital, while two authors, Zhanyi Sun and Jinju Jiang, were affiliated with the State Key Laboratory of Bioactive Seaweed Substances at Qingdao Brightmoon Seaweed Group Co Ltd, a company operating in the seaweed products industry. Fucoidan research frequently involves such partnerships, because seaweed processors hold both the raw material and the extraction expertise, while clinical departments provide the disease models and the translational motivation. The retraction does not attribute the image problems to any particular affiliation, but the structure of the collaboration illustrates how enthusiasm for a commercially relevant natural product can move a manuscript quickly from the laboratory to publication.

For readers who followed the original findings, the retraction matters because fucoidan has been promoted in some circles as a dietary supplement with anticancer potential, and laboratory papers like this one are often cited in support of such claims. The retracted study reported that fucoidan suppressed lung cancer cell proliferation and modulated the expression of proteins including Cyclin D1 and components of the mTOR pathway, a mechanistic story that fit neatly with the broader narrative that seaweed polysaccharides can restrain the signaling circuits that tumors depend on. With the paper retracted, that specific body of evidence can no longer be relied upon, and citations of it in reviews or meta-analyses should be removed or flagged in accordance with retraction guidelines.

The case also illustrates the technical fingerprints that image-integrity screening has become adept at detecting. Western blot figures are assembled from multiple exposures and panels, and when the same band, or a portion of one, appears in more than one place with different labels, duplication-detection software and attentive readers can identify the overlap even when the images have been flipped, cropped, or adjusted for contrast. In this instance, the reported similarities involved both a within-figure duplication, where one band allegedly represented two different proteins, and cross-panel duplication between the two cell lines, a combination that is difficult to explain as an innocent laboratory error. The failure of most of the author team to engage with the concerns meant that no alternative explanation was ever placed on the record.

The editors’ decision follows the standard logic of research self-correction: when the primary evidence for a conclusion is compromised and the authors cannot or will not defend it, the conclusion must be withdrawn from the scientific record regardless of how plausible it may seem. Retraction does not prove that fucoidan has no antitumor activity, and other independent studies of seaweed-derived compounds continue in laboratories around the world. What it does establish is that this particular dataset, produced with the involvement of a seaweed industry laboratory and published in a complementary medicine journal, cannot support the claims it was published to make. For patients and clinicians weighing marine-derived supplements as part of cancer care, the episode is a reminder that the evidence base for such compounds must be judged study by study, and that retracted papers, however widely they once circulated, no longer count as evidence at all.

Subject of Research: Retraction of a study on the antitumor effect and molecular mechanism of fucoidan in non-small cell lung cancer

Article Title: Retraction Note: Antitumor effect and molecular mechanism of fucoidan in NSCLC

Article References: Chen, X., Sun, L., Wei, X., Lu, H., Tan, Y., Sun, Z., & Jiang, J. (2026). Retraction Note: Antitumor effect and molecular mechanism of fucoidan in NSCLC. BMC Complementary Medicine and Therapies, 26(1), Article 310. https://doi.org/10.1186/s12906-026-05648-0

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05648-0

Keywords: fucoidan, retraction, non-small cell lung cancer, western blot, image duplication, research integrity, Cyclin D1, mTOR, A549, H1650, seaweed extract, BMC Complementary Medicine and Therapies

Atherosclerosis, the slow accumulation of lipid-rich plaques inside artery walls, remains a leading driver of heart attacks and ischemic stroke. Two forces dominate its progression: chronically elevated cholesterol and persistent low-grade inflammation. When a high-fat diet floods the bloodstream with triglyceride-rich lipoproteins, these particles lodge in the vascular endothelium, triggering inflammatory signals that recruit immune cells. Monocytes differentiate into macrophages, which engulf lipids and swell into foam cells — the cellular hallmark of early arterial lesions. Current lipid-lowering drugs, including statins, ezetimibe, and PCSK9 inhibitors, have transformed cardiovascular care, but they carry limitations: statins can burden the liver, and ezetimibe’s effect is comparatively modest. That gap has pushed researchers toward dietary bioactives that could complement or reduce reliance on pharmaceuticals.

Fucoidan, a fucose-based polysaccharide studded with sulfate groups, is found in brown seaweeds and marine invertebrates. It has attracted attention for anti-inflammatory, lipid-lowering, and immune-modulating properties, with a generally favorable safety profile. Prior work by the same team had already shown that fucoidan from Pearsonothuria graeffei (Fuc-Pg) could reshape gut microbiota and dampen intestinal and colonic inflammation in obese mice. But whether it could slow atherosclerosis itself — and by what route — remained unresolved. The new study set out to answer both questions in a single experimental framework.

The researchers used ApoE-deficient mice, a standard model in which the absence of apolipoprotein E makes animals exquisitely vulnerable to diet-induced arterial plaques. Thirty-two of these mice were fed a high-fat diet containing 42% of calories from fat and 1.5% cholesterol for twelve weeks. They were divided into four groups: an untreated model group, a group receiving 20 mg/kg of simvastatin, and two groups receiving Fuc-Pg at 20 or 80 mg/kg by daily oral gavage. Eight normal C57BL/6J mice on a standard diet served as healthy controls. At the end of the trial, the team collected blood, liver, aorta, and small intestine for biochemical, histological, and molecular analysis.

The results were striking. Untreated ApoE-deficient mice on the high-fat diet gained significantly more weight and developed the expected dyslipidemic signature: elevated total cholesterol, triglycerides, and LDL-C, with depressed HDL-C. High-dose Fuc-Pg markedly reversed this pattern, lowering TC, TG, and LDL-C more effectively than the low dose. Notably, simvastatin — the positive control — failed to improve the lipid profile in these mice, a result consistent with earlier reports that statin efficacy can be blunted under a heavy dietary fat load and may depend on functional ApoE protein, which these mice lack. Oil Red O staining of the aorta told a similar story: untreated mice showed extensive red plaques from the aortic arch to the abdominal aorta, while high-dose Fuc-Pg produced a statistically significant reduction in plaque area, particularly in the aortic arch.

Inflammation, a key accelerant of plaque growth, also receded under Fuc-Pg treatment. Serum levels of the pro-inflammatory cytokines IL-1β and TNF-α, along with the chemokine MCP-1, were substantially elevated in the model group but dropped sharply with Fuc-Pg intervention. Hepatic mRNA levels of IL-1β and TNF-α followed the same trend. Simvastatin, by contrast, showed no meaningful effect on these inflammatory markers, underscoring that Fuc-Pg’s benefit extends beyond lipid numbers alone.

To understand how the compound works, the team turned to the intestine — the first checkpoint for dietary fat. Enterocytes absorb fatty acids and cholesterol and package them into chylomicrons, lipoprotein particles that enter the lymphatic system and eventually the bloodstream. Two proteins are central to this process: CD36, a fatty acid transporter on the cell surface, and microsomal triglyceride transfer protein (MTP), which assembles dietary lipids into pre-chylomicron particles. In the duodenum of untreated mice, both CD36 and MTP were markedly upregulated. High-dose Fuc-Pg suppressed both, effectively throttling the assembly line that converts a fatty meal into circulating lipid cargo. The team also observed increased fecal excretion of cholesterol and triglycerides, confirming that less dietary lipid was being absorbed and more was passing through the gut unprocessed.

In the liver, Fuc-Pg shifted cholesterol traffic in the opposite direction — toward export. Reverse cholesterol transport (RCT) is the process by which excess cholesterol from peripheral tissues is returned to the liver for elimination, either through biliary secretion or conversion into bile acids. The hepatic LDL receptor (LDLR), which clears more than 70% of circulating LDL particles from the blood, was upregulated at both mRNA and protein levels with Fuc-Pg treatment. The ABCG5/ABCG8 transporter pair, which pumps cholesterol from hepatocytes into bile, was also elevated. Together, these changes suggest that Fuc-Pg helps the liver pull cholesterol out of circulation and push it toward excretion, relieving the hepatic lipid deposition that otherwise fuels dyslipidemia and arterial disease.

The third arm of the mechanism involves bile acids. Cholesterol converted into bile acids represents one of the body’s main routes for disposing of excess sterol. Fuc-Pg increased hepatic total bile acid levels and boosted the expression of CYP7A1 and CYP27A1 — the rate-limiting enzymes of the classic and alternative bile acid synthesis pathways, respectively. Upstream, the compound elevated PGC1α and HNF4α, nuclear regulators that synergistically activate CYP7A1 transcription. Mass spectrometry profiling revealed shifts in the bile acid pool, including a notable rise in tauroursodeoxycholic acid (TUDCA), which protects hepatocytes from endoplasmic reticulum stress and apoptotic signaling, and tauro-beta-muricholic acid (TβMCA), a hydrophilic species that dilutes the toxicity of more hydrophobic bile acids. Meanwhile, serum bile acid levels trended downward rather than spiking — a reassuring sign that the liver was handling the increased synthetic load without leaking bile acids into circulation, which would indicate injury.

The study is not without caveats. The ApoE-deficient mouse model, while classic, does not fully recapitulate human atherosclerotic pathology, and the simvastatin control’s underperformance — likely a quirk of the model rather than a flaw in statins themselves — complicates direct comparisons with clinical practice. Still, the findings position Fuc-Pg as a structurally well-characterized marine polysaccharide with a coherent, multi-organ mechanism: it throttles lipid entry at the gut, accelerates cholesterol clearance in the liver, and funnels the surplus into bile acid synthesis for safe elimination. For a field hungry for dietary strategies that complement existing drugs, that combination of specificity and mechanistic depth makes sea cucumber fucoidan a compound worth watching as research moves from mouse models toward functional food applications.

Subject of Research: atherosclerosis

Article Title: Fucoidan from Pearsonothuria graeffei alleviates dyslipidemia in ApoE−/− mice by regulating reverse cholesterol transport and promoting bile acid synthesis

Article References: Zhao, T., Yu, Y., Wang, Y., Zhang, L., Xiao, J., Chen, S., & Li, S. (2026). Fucoidan from Pearsonothuria graeffei alleviates dyslipidemia in ApoE−/− mice by regulating reverse cholesterol transport and promoting bile acid synthesis. Frontiers in Nutrition, 13, 1974149. https://doi.org/10.3389/fnut.2026.1974149

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1974149

Keywords: fucoidan, atherosclerosis, cholesterol metabolism, bile acids, reverse cholesterol transport, sea cucumber, dyslipidemia, functional foods, Pearsonothuria, graeffei, alleviates, ApoE

Food scientists have long tried to solve this with encapsulation, wrapping sensitive molecules in protective carriers that shield them in the stomach and release them further down the line. Gel-based delivery systems have emerged as a leading strategy, but most of them share a common flaw. They typically rely on differential swelling: the gel swells more in the intestine than in the stomach, allowing some cargo to escape. The problem is that the matrix itself often survives the intestinal stage largely intact, trapping a substantial fraction of the anthocyanins inside. Previous systems built from gelatin and gellan gum, or from peptides and whey protein isolate, achieved respectable but incomplete release, leaving a meaningful portion of the payload locked away in a structure that never fully fell apart.

A research team led by Wenjun Li and colleagues has now reported a solution in Food Chemistry: X that hinges on an unusual ingredient from the sea: fucoidan, a sulfated polysaccharide extracted from brown seaweeds. The key insight lies in electrostatics. In an earlier study, the group had built gelatin-pectin gels in which pectin’s carboxyl groups, with a pKa of roughly 3.5, flip from mostly uncharged in the acidic stomach to strongly negatively charged in the near-neutral intestine. That charge shift drove electrostatic repulsion and partial network collapse, releasing about 80 percent of the encapsulated anthocyanins. Impressive, but not complete. Fucoidan offered something better: its sulfate ester groups carry pKa values of only about 0.5 to 2.0, meaning they remain aggressively anionic across virtually the entire gastrointestinal pH range.

The team’s hypothesis was elegant. Gelatin, a protein derived from collagen, carries a positive charge under strongly acidic conditions. Pair it with fucoidan in the stomach, and the opposite charges attract, compensating one another and locking the network into a stable, self-supporting gel. Shift to intestinal pH, however, and fucoidan’s sulfate groups become massively negative while gelatin’s positive charge fades. The once-balanced composite turns strongly anionic, electrostatic repulsion takes over, and the network destabilizes, potentially disintegrating so thoroughly that nearly all of the anthocyanins are freed. To test this, the researchers prepared a systematic matrix of 25 formulations, varying total solid content from 2 to 10 percent and the gelatin-to-fucoidan mass ratio from 9:1 down to 5:5.

The characterization work revealed clear rules of composition. Rheological measurements showed that all gel-forming formulations behaved as true elastic gels, with the storage modulus exceeding the loss modulus, and that stiffness climbed steadily with solid content. Hardness testing with a texture analyzer confirmed the same trend: more solids meant more internal crosslinking and greater mechanical strength. Scanning electron microscopy of a representative 10 percent gel revealed the porous, interconnected three-dimensional architecture that gives hydrogels their capacity to harbor small molecules. Not every combination worked, however. The 5:5 gelatin-fucoidan mixtures failed to form self-supporting gels at any solid content, and the 2 percent formulations were too soft to measure reliably, establishing that a sufficient gelatin fraction is essential to build the continuous network in the first place.

Encapsulation performance was striking across the board. Every stable gel-forming formulation captured more than 95 percent of the added anthocyanins, with the best result, 98.77 percent, achieved by the 10 percent gel at a 6:4 ratio. Fluorescence microscopy showed the pigments distributed uniformly throughout the matrix with no aggregation. Storage tests over 14 days demonstrated that encapsulated anthocyanins retained far more of their color and content than free anthocyanins, particularly under light exposure, where unprotected pigments degrade fastest. The gel was not just a delivery vehicle but also a preservative, extending the shelf-life stability of the compounds it carried.

The electrostatic story played out exactly as predicted. Zeta potential measurements showed that at pH 1.5, gelatin carried a positive charge of about +7 millivolts while fucoidan was mildly negative, and the composite sat near neutral at +2 millivolts, the signature of charge compensation. At pH 6.8, fucoidan plunged to −42.2 millivolts and the composite shifted to −20.6 millivolts, a distinctly anionic state primed for repulsion-driven collapse. Correspondingly, in simulated gastric fluid the gels swelled moderately but held their macroscopic shape for the full two-hour digestion, while in simulated intestinal fluid they dissolved dramatically, with the softest formulations vanishing within an hour. Control experiments at body temperature confirmed that the 10 percent composite gel remained self-supporting in gastric conditions yet disintegrated in intestinal fluid, showing the response was not merely an artifact of gelatin’s thermal softening.

The release data delivered the headline result. The standout formulation, containing 10 percent solids at an 8:2 gelatin-to-fucoidan ratio, leaked only 3.50 percent of its anthocyanins during the gastric stage, then released 99.94 percent of the total payload after intestinal exposure, essentially complete liberation within experimental error. Neighboring high-solid formulations at 9:1 and 7:3 ratios performed nearly as well, at 99.11 and 98.08 percent. For context, the team’s earlier gelatin-pectin system managed 87.87 percent intestinal release with 10.70 percent gastric leakage, and a dual-crosslinked apricot polysaccharide hydrogel reached about 87 percent cumulative release. The new system outperformed both benchmarks on gastric retention and intestinal delivery simultaneously, resolving the trade-off that had limited earlier designs.

Kinetic modeling added mechanistic texture to the findings. Fitting the release profile to five standard models showed that the Logistic model described the sigmoidal, stage-dependent behavior best, with an R-squared of 0.998, capturing the quiet gastric phase, the sharp surge after the pH transition, and the final plateau. The Ritger-Peppas exponent of about 1.07, though a weaker fit, pointed toward release governed by structural changes in the matrix rather than simple diffusion, consistent with the visual evidence of network disintegration coinciding with the release surge. Together, the kinetics and microscopy painted a coherent picture: anthocyanin liberation is driven not by passive swelling but by the active, pH-triggered dismantling of the gel network itself.

Beyond the immediate result, the study offers a design framework with broader implications. It demonstrates that the responsive element of a delivery gel can be tuned by choosing polysaccharides with different ionizable group chemistries, and that sulfate-rich marine polysaccharides deserve a central place in that toolkit. The composition rules matter too: more fucoidan is not automatically better, because the network-forming capacity of gelatin and the electrostatic responsiveness of fucoidan must be balanced. The authors note that the roles of digestive enzymes, bile components, and intestinal ions in modulating release still merit targeted investigation before such systems reach real foods. But the principle is now established: with the right polymer pairing and the right recipe, a food-grade gel can guard delicate plant pigments through the stomach’s acid bath and then dissolve almost completely where the body can actually use them.

Subject of Research: pH-responsive gelatin-fucoidan composite hydrogels for gastrointestinal delivery of anthocyanins

Article Title: Composition-guided design of Gelatin-fucoidan composite gels for gastric anthocyanin retention and intestinal release

Article References: Li, W., Li, J., Zeng, Q., Chen, W., Chen, X., Huang, Y., & Yang, W. (2026). Composition-guided design of Gelatin-fucoidan composite gels for gastric anthocyanin retention and intestinal release. Food Chemistry: X, 39, Article 104538. https://doi.org/10.1016/j.fochx.2026.104538

Image Credits: AI Generated

DOI: 10.1016/j.fochx.2026.104538

Keywords: anthocyanins, fucoidan, gelatin, hydrogels, drug delivery, bioavailability, pH-responsive, electrostatics, food chemistry, encapsulation, marine polysaccharides, simulated digestion

What makes marine carbohydrates so chemically interesting is their structural diversity. Polysaccharides extracted from seaweeds, sponges, shellfish and marine bacteria can carry sulfate groups in patterns that differ from species to species, form glycosidic linkages that are uncommon in terrestrial plants, and adopt branched architectures that change how they interact with biological targets. Fucoidans from brown algae, carrageenans from red algae, chitin and chitosan derivatives from crustacean shells, and sulfated glycosaminoglycan-like molecules from marine animals all fall into this category. Because the precise arrangement of sulfate groups and sugar units determines how these molecules bind to proteins, enzymes and cell surfaces, even subtle structural differences can translate into dramatically different biological effects.

That sensitivity to structure is precisely why these molecules have attracted attention across so many therapeutic areas. The review documents reported antiviral, anticoagulant, immunomodulatory and antitumor activities for marine-derived carbohydrates and their derivatives, alongside material properties that make them useful in drug delivery systems, wound dressings and tissue engineering scaffolds. Sulfated polysaccharides, for example, can interfere with viral attachment and entry by mimicking the charged surfaces that viruses normally latch onto, while alginate-based materials have become mainstays in encapsulation and wound-care applications because of their gentle gelling behavior and biocompatibility.

The clinical story of marine-inspired drugs is older than many readers might expect. The review’s authors anchor their timeline to cytarabine, an antileukemia drug approved in the United States in 1969, which traces its chemical inspiration to nucleosides originally isolated from a Caribbean sponge. Although cytarabine is not itself a carbohydrate in the polysaccharide sense, it established a crucial precedent: molecules derived from marine organisms could survive the full gauntlet of preclinical testing, regulatory scrutiny and clinical use. Later products built on alginate, carrageenan and other marine raw materials followed, extending the family of carbohydrate-based medicines into areas such as wound management, drug formulation and symptomatic treatment.

Today, the pipeline is broader than ever. The review surveys clinical-stage candidates derived from marine carbohydrates currently being evaluated for viral infections, cancer, metabolic disorders, tissue repair, cystic fibrosis and neurological disease. This breadth reflects both the versatility of the molecules and the maturity of the field: what was once a collection of exploratory extracts has become a portfolio of defined candidates moving through controlled trials. Yet the authors are careful to note that the distance between a promising laboratory result and an approved product remains substantial, and that the obstacles are not primarily about discovering new activities.

The central challenge, according to the review, is reproducibility. The biological activity of a marine polysaccharide depends on its molecular weight, its sulfation pattern and its monosaccharide composition, but all three of these parameters can vary with the species from which the material is harvested, the season in which it is collected, and the extraction and processing methods used to isolate it. A batch of fucoidan gathered from one coastline in spring may differ measurably from a batch of the nominally same polymer collected elsewhere in autumn. For a regulatory agency, such variability is a serious problem, because a drug must deliver the same molecule, with the same quality attributes, every single time.

Solving that problem requires the kind of systematic thinking that the review tries to encourage. The authors argue that marine carbohydrates have too often been studied in terms of individual biological activities, with each research group reporting a single effect in isolation, while clinical development demands an integrated understanding of how structure, production, quality control and mechanism of action fit together. A candidate cannot advance if researchers cannot define its composition precisely, manufacture it consistently and explain how it works at the molecular level. The review therefore treats approved drugs and clinical candidates not just as success stories, but as case studies in how these elements can be aligned.

The priorities for future development that the authors identify are correspondingly practical. They call for reliable production methods based on cultivation, fermentation or enzymatic processing, which would decouple drug supply from wild harvesting and reduce batch-to-batch variation. They emphasize the need for improved quality control that combines structural characterization with activity-based assays, so that manufacturers can verify not only what a batch contains but what it does. They also stress the importance of validating molecular targets and mechanisms of action, and of conducting more rigorous pharmacokinetic and safety studies, areas in which complex carbohydrates have historically lagged behind small-molecule drugs because of their size, heterogeneity and analytical difficulty.

Achieving these goals, the review concludes, will require collaboration across disciplines that do not always work together. Senior and co-corresponding author Guangli Yu of the Ocean University of China notes that progress will depend on close cooperation among researchers in glycoscience, analytical chemistry, synthetic biology, materials science and clinical research. Co-corresponding author Chao Cai, also of the Ocean University of China, shares responsibility for the work, which was conducted within the Key Laboratory of Marine Drugs under the Ministry of Education and the Shandong Key Laboratory of Glycoscience and Glycotherapeutics. The interdisciplinary framing is deliberate: no single field currently possesses all the tools needed to characterize, manufacture and clinically validate a heterogeneous natural polymer.

The significance of the review lies less in any single discovery than in its synthesis. By following a clinical timeline that stretches from a 1969 leukemia drug to today’s trials in virology, oncology, metabolic disease and neurology, it demonstrates that marine carbohydrate therapeutics are not a speculative frontier but an evolving branch of pharmacology with a documented track record. The structural uniqueness of ocean-derived sugars, once a curiosity, is now understood as a design resource, and the field’s remaining challenges are the familiar ones of manufacturing, characterization and clinical evidence. If the collaborative agenda the authors describe takes hold, the next chapters of this timeline may be written not by chance discoveries in tide pools, but by engineered production systems capable of delivering the ocean’s chemistry with pharmaceutical precision.

Subject of Research: Marine carbohydrate-based drug development and clinical translation

Article Title: Marine carbohydrate therapeutics: from structural diversity to clinical translation

Article References: Marine carbohydrate therapeutics: from structural diversity to clinical translation. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: marine carbohydrates, polysaccharides, fucoidan, alginate, carrageenan, drug development, clinical trials, glycoscience, sulfation, antiviral, anticoagulant, Ocean University of China

The strategy grew out of a long-standing interest in cellular senescence, a stress response that permanently halts cell division. Senescent cells are famously double-edged. When a cell accumulates dangerous damage, senescence shuts it down before it can become cancerous, and during wound healing, senescent cells coordinate repair by broadcasting signals that recruit other cells to the injury site. The trouble begins when these cells overstay their welcome. Instead of quietly disappearing once their job is done, lingering senescent cells keep emitting inflammatory and profibrotic signals that drive chronic inflammation and scarring. Scott Lowe, who chairs the Cancer Biology and Genetics Program at MSK’s Sloan Kettering Institute and is a Howard Hughes Medical Institute investigator, has spent years probing this duality. The therapeutic dream, he explains, is to clear the harmful senescent cells while sparing the helpful ones—a goal that has proven difficult because senescent cells in different contexts can look deceptively similar.

The breakthrough came when the researchers examined macrophages, the scavenger immune cells that patrol tissues, in fibrotic environments. Within these populations, they identified a small subset expressing a surface protein called P-selectin alongside multiple molecular hallmarks of senescence. The team dubbed these cells MΦP+sen+—macrophages that are both P-selectin positive and senescence positive. What struck the scientists was their consistency: the same distinctive population appeared in fibrotic tumor niches in liver and lung cancers and in heavily scarred liver and lung tissue, and its presence correlated with poorer responses to immunotherapy in patients. Clemens Hinterleitner, a postdoctoral researcher and co-first author of the study, notes that finding this specific macrophage population so reliably in fibrotic tissue was remarkable, and that its presence signaled a compromised local immune environment.

These cells are far more than innocent bystanders. According to the study, MΦP+sen+ macrophages contribute to the fibrosis that forms a physical barrier around tumors, and they simultaneously dampen the activity of neighboring immune cells by sending out profibrotic and immunosuppressive signals. Co-first author Valentin Barthet describes them as actively erecting a wall that prevents the immune system from doing its job. The cells make up only about 3 to 5 percent of fibrotic tissue, yet experiments in mouse models of liver and lung fibrosis and fibrotic liver and lung cancers showed that selectively killing them or silencing their signals had a profound effect on fibrosis. The team validated the key findings in tumor samples from lung cancer patients treated at MSK and in human lung and liver cancer datasets, lending clinical weight to the mouse data.

The consequences of eliminating or disabling these macrophages were dramatic. The scar tissue shielding the tumor began to dissolve, and the suppression of other immune cells eased. Freed from both the physical and chemical barriers, checkpoint inhibitor immunotherapy—the class of drugs that unleashes T cells against cancer—suddenly worked in mice, shrinking tumors that had previously been resistant to treatment. In other words, the intervention did not attack the cancer cells directly. It removed the ecosystem support that allowed the tumor to hide, converting a cold, immune-excluded tumor microenvironment into one that existing therapies could penetrate.

Delivering a lethal payload to such a small and specific cell population posed a formidable engineering challenge, and this is where the collaboration with Daniel Heller’s biomedical engineering lab proved decisive. Heller’s group had previously developed a nanoparticle platform that targets P-selectin, and the team adapted it with new drugs and a new mission. The particles are roughly a thousand times smaller than the width of a human hair and are coated with fucoidan, a naturally occurring sugar molecule found in brown seaweed and sold as an anti-inflammatory supplement. Fucoidan binds specifically to P-selectin, ensuring that the nanoparticles are taken up not by just any macrophage but by the precise P-selectin-positive subset driving the fibrosis. When the targeted macrophages ingest and digest a particle, the drug inside is released—an effect Heller likens to soldiers springing from a Trojan Horse to launch a precision attack from within.

The researchers loaded the nanoparticles with two drugs that are potent against senescent cells but have been hampered by toxicity in clinical use. The first, Navitoclax, exploits a vulnerability in senescent cells’ survival machinery: these stressed cells block their own natural self-destruct program, and Navitoclax removes that block, causing them to die. The second, a BET inhibitor called dBET6, takes a different tack—it silences the inflammatory signals that senescent cells broadcast into surrounding tissue. With the alarm switched off, the cells stop producing the signals that drive fibrosis and immune suppression, even though the cells themselves survive. Both drugs had shown promise against cellular senescence in the laboratory but failed clinically because, when administered conventionally, they damage healthy cells and tissues throughout the body. In the mouse experiments, the nanoparticle-packaged versions appeared safe and did not produce the same toxicity, raising the possibility that targeted delivery could give both drugs a second chance in the clinic.

The implications may extend well beyond liver and lung cancer. Searching a large database of immune cell profiles, the researchers found the same harmful macrophage population associated with breast and colon cancers as well as chronic inflammatory diseases including osteoarthritis and rheumatoid arthritis. Aveline Filliol, a senior scientist in the Lowe Lab and co-corresponding author, points out that these macrophages also share important features with lipid-associated macrophages, a cell type found in the atherosclerotic plaques that cause heart disease—suggesting the platform could one day be adapted to deliver drugs to those cells as well. If MΦP+sen+ cells prove to be a common culprit across many diseases, a single nanoparticle platform, retargeted with different drug cargoes, could address an unusually wide range of conditions united by a shared cellular mechanism.

Beyond the specific findings, the work exemplifies an increasingly influential strategy in oncology: targeting the cancer ecosystem rather than the tumor cells alone. Cancer cells, Lowe argues, do not act in isolation; building a tumor-supportive environment requires coordinated interactions between malignant cells and the surrounding tissue, and disrupting those interactions represents a significant new frontier. The study also showcases the kind of interdisciplinary collaboration—between biologists and engineers, and between bench scientists and clinicians—that allowed the team to move from a biological observation to an engineering solution to validation in human tissue within a single institution. MSK is now seeking commercialization partners to advance the research into clinical trials, first in cancer and potentially in other fibrotic and inflammatory diseases. A patent application covering the use of fucoidan nanoparticles to treat senescence-associated pathologies has been published, and related intellectual property has been granted, signaling that the road from laboratory insight to patient benefit is already under construction. If the approach survives the rigors of human testing, it could offer a way to make immunotherapy work for the many patients it currently fails—and to treat the scarred, inflamed tissue that underlies diseases far beyond cancer.

Subject of Research: Senescence-directed nanoparticle targeting of fibrosis-driving macrophages to overcome immune exclusion in cancer

Article Title: Using nanoparticles to target fibrosis in cancer and other diseases

Article References: Using nanoparticles to target fibrosis in cancer and other diseases. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: nanoparticles, fibrosis, cellular senescence, macrophages, immunotherapy, cancer, P-selectin, fucoidan, Navitoclax, BET inhibitor, tumor microenvironment, checkpoint inhibitors

MASLD is no longer a niche concern. It encompasses a spectrum running from simple hepatic steatosis to the inflammatory, fibrotic condition known as metabolic dysfunction-associated steatohepatitis, and it is tightly coupled to obesity and type 2 diabetes. Treatment options remain frustratingly thin. The recent approval of resmetirom, a thyroid hormone receptor-beta agonist that became the first FDA-approved medication for nonalcoholic steatohepatitis, marked a genuine milestone, but clinicians still lack cheap, safe, preventive strategies for the vast population of patients with early disease. That gap has pushed researchers toward nutraceuticals—food-derived compounds with drug-like activity—and toward the gut microbiome as a therapeutic target in its own right.

The gut–liver axis sits at the center of the new review’s argument. The liver receives the portal blood supply directly from the intestine, along with everything the gut microbes produce: short-chain fatty acids, bile acid derivatives, trimethylamine N-oxide, indole compounds, endotoxins, and ethanol made by bacteria themselves. When the microbial community falls into dysbiosis—a state that clinical studies have repeatedly linked to the severity of fatty liver disease—the balance of these metabolites tips. Barrier function in the intestine weakens, bacterial lipopolysaccharide leaks into circulation, hepatic inflammation and oxidative stress escalate, and hepatocytes accumulate fat. Some evidence even implicates high-alcohol-producing Klebsiella pneumoniae in driving fatty liver in non-drinkers, underscoring how directly microbial chemistry can become hepatic pathology.

What makes marine polysaccharides different from the plant fibers already celebrated in nutrition? The authors emphasize structural chemistry. Land-based fibers are built largely from neutral sugars, whereas marine polysaccharides—fucoidans from brown seaweeds, carrageenans from red algae, ulvans from green algae, agars and porphyrans from Porphyra, alginates from kelp, chitosan from crustacean shells, and sulfated glycans from sea cucumbers—carry sulfate groups and uronic acids, form complex glycosidic linkages, adopt diverse conformations, and span broad molecular-weight distributions. Those features mean that human enzymes cannot digest them, but specific gut bacteria can, using elaborate carbohydrate-active enzyme systems called polysaccharide utilization loci. The result is selective feeding: particular structures recruit particular microbial taxa, shifting community composition in reproducible, mechanism-linked ways.

Human populations provide a striking natural experiment. Japanese individuals harbor gut bacteria that acquired genes for digesting marine sulfated polysaccharides from marine Bacteroides via horizontal gene transfer, a discovery that revealed how the microbiome can expand its metabolic repertoire when the diet supplies novel glycans. Subsequent genomic work identified multiple independent transfer events that seeded seaweed-digestion genes into human gut bacteria. This capacity for adaptation is precisely what marine polysaccharide therapy hopes to exploit: by supplying glycans that only beneficial consumers can process, these compounds act as targeted prebiotics, enriching organisms such as Lactobacillus, Akkermansia muciniphila, and beneficial Bacteroides species while suppressing inflammatory lineages.

The downstream metabolic consequences are where the review gets technically ambitious. Fermentation of marine polysaccharides yields short-chain fatty acids—acetate, propionate, and butyrate—which nourish colonocytes, strengthen tight junctions, and engage G-protein-coupled receptors that regulate glucose homeostasis and appetite. Simultaneously, polysaccharide-driven changes in bile acid metabolism alter signaling through the nuclear receptor FXR and the membrane receptor TGR5, pathways now recognized as central to hepatic lipid handling, energy expenditure, and inflammation. At the hepatocyte level, marine polysaccharides and their oligosaccharide fragments activate AMPK and PPARα, the master switches of fatty acid oxidation, and engage the Nrf2 antioxidant program, directly countering the lipid accumulation and oxidative stress that define steatohepatitis.

Preclinical evidence illustrates the breadth of this approach. Fucoidan from Sargassum fusiforme alleviated high-fat diet-induced obesity and insulin resistance while improving the gut microbiota profile and hepatic oxidative stress. Alginate oligosaccharides relieved insulin resistance and fatty liver in mice through microbiota-mediated bile acid regulation. Iota-carrageenan tetrasaccharide reduced liver lipid accumulation via the bile acid–FXR–SHP/PXR pathway, and chitosan oligosaccharides attenuated steatosis, inflammation, and oxidative stress in diet-induced obese mice. Sea cucumber fucosylated chondroitin sulfate modified gut microbiota to prevent obesity, and oyster polysaccharide ameliorated hepatic oxidative stress through the bile acid–FXR–AMPKα axis. Porphyran from discolored nori prevented metabolic syndrome through a microbiota–bile acid–ceramide pathway, while ulvan oligosaccharides regulated lipid metabolism in high-fat diet-fed animals.

Clinical data, though still early, are encouraging. A randomized, double-blinded, placebo-controlled trial found that chitosan supplementation improved liver function, hepatic steatosis predictors, and metabolic indicators in adults with non-alcoholic fatty liver disease. Chitooligosaccharides rebalanced gut microorganisms and their metabolites in NAFLD patients, and Icelandic trial data showed that chitosan supplementation favorably altered the gut microbiota in healthy women. A fucoidan extract improved insulin resistance and cardiometabolic markers in obese, nondiabetic subjects in a randomized controlled trial, and fucoidan has also demonstrated clinical efficacy as an adjunct in Helicobacter pylori eradication, hinting at broad microbiome-modulating potential. Trials combining Laminaria japonica with probiotics improved intestinal microbiota in human volunteers, and fecal microbiota transplantation protocols now being tested in steatohepatitis underscore how central microbial manipulation has become to the field.

The review is candid about the obstacles between laboratory promise and clinical reality. Marine polysaccharides are structurally heterogeneous, and batch-to-batch variation in sulfation pattern, molecular weight, and monosaccharide composition makes standardization difficult—yet those same variables appear to determine biological activity, as shown by recent synthetic fucoidan libraries that enabled systematic structure–function comparisons. Safety questions also persist, particularly for carrageenan, a widely used food additive whose degraded forms have been associated with intestinal inflammation in some animal and human studies, even as food-grade material appears benign in others; clarifying this controversy is essential for consumer confidence. Contaminant burdens in macroalgae, including arsenic, cadmium, lead, and mercury, require careful regulatory alignment between producing and consuming regions. Dosing, bioavailability, and long-term effects remain underexplored.

Nevertheless, the authors position marine polysaccharides as uniquely advantaged relative to terrestrial fibers: their unusual chemistries reach microbial niches that common fibers cannot, and their pleiotropic effects—spanning short-chain fatty acid production, bile acid signaling, barrier protection, endocrine modulation, and direct hepatic pathway activation—map precisely onto the multi-organ pathophysiology of MASLD. As sequencing technologies make it possible to identify exactly which bacteria consume which glycans, and as controlled synthesis enables reproducible materials, the field is converging on a rational design framework: engineer polysaccharide structures to recruit defined beneficial communities and thereby steer the gut–liver axis away from disease. If clinical trials confirm the early human signals, the humble slime of the seashore may prove to be one of the most practical liver medicines of the coming decade—harvested not from a pharmaceutical plant, but from the wrack line.

The scale of the unmet need gives this research agenda its urgency. Population studies suggest that roughly a third of adults in many industrialized countries carry hepatic steatosis, with prevalence climbing in children and adolescents, yet most affected individuals are identified only incidentally or through rising cardiometabolic risk factors. Because early-stage disease is largely asymptomatic, an intervention that could be delivered safely as a dietary supplement—and taken for years—would address a far larger population than any prescription drug realistically can.

The prebiotic framing deserves careful attention. Classic prebiotics such as inulin and fructooligosaccharides are fermented broadly by common saccharolytic organisms, which can limit how precisely a community can be steered. Sulfated marine glycans, by contrast, demand specialized enzyme machinery, so only microbes equipped with the appropriate sulfatases and carbohydrate-active enzymes can access them. This substrate specificity is the theoretical basis for precision microbiome editing through diet, and it explains why the authors treat structural chemistry rather than fiber content as the decisive design variable.

Molecular weight emerges as a recurring theme in the preclinical literature. High-molecular-weight polymers are often poorly soluble and difficult for microbes to process, while controlled depolymerization into oligosaccharides frequently enhances water solubility, bioactivity, and fermentability. Several of the most striking animal results cited in the review involve oligosaccharide fragments rather than intact polymers, suggesting that processing technology—enzymatic degradation, controlled hydrolysis, or even synthetic chemistry—will be as important as source selection for future products.

Practical considerations also favor the field. Many marine polysaccharides already hold food additive or generally recognized as safe status in major jurisdictions, and industrial supply chains for carrageenan, alginate, and agar are mature, which could shorten the path from bench to consumer. Seasonal and geographic variation in seaweed composition remains a genuine hurdle, but cultivation of defined macroalgal strains under controlled conditions offers a route to more consistent raw material than wild harvest alone.

What remains most persuasive is the convergence of mechanisms: microbial selection, metabolite generation, barrier reinforcement, and direct hepatic signaling all point in the same direction. Few nutraceutical candidates offer that degree of mechanistic coherence, and few target a disease with such a large and growing affected population.

Subject of Research: Marine polysaccharides as nutraceutical modulators of the gut microbiome and gut–liver axis in metabolic dysfunction-associated steatotic liver disease

Article Title: Marine polysaccharides: promising nutraceuticals for metabolic dysfunction-associated steatotic liver disease as unique and potent modulator of gut microbiome

Article References: Pan, Y., Zhang, R., & Chen, Y. (2026). Marine polysaccharides: promising nutraceuticals for metabolic dysfunction-associated steatotic liver disease as unique and potent modulator of gut microbiome. Food Science and Biotechnology. https://doi.org/10.1007/s10068-026-02283-w

Image Credits: AI Generated

DOI: 10.1007/s10068-026-02283-w

Keywords: marine polysaccharides, MASLD, gut microbiome, gut–liver axis, fucoidan, carrageenan, ulvan, chitosan, short-chain fatty acids, bile acid signaling, nutraceuticals, fatty liver disease

The chemical arsenal on display is remarkable in its diversity. Brown algae of the class Phaeophyceae are dominated by phlorotannins, polyphenolic polymers built from phloroglucinol units and linked through ether, phenyl and dibenzodioxin bonds. The degree of polymerisation governs both solubility and bioactivity, and roughly 220 phlorotannin entries are catalogued in the Seaweed Metabolite Database. Red algae, which show the highest fingerprint diversity in that database with 645 recorded metabolites, specialise in sulfated galactans such as carrageenans and in an extraordinary array of halogenated terpenes and acetogenins, exemplified by compounds like elatol and isolaurinterol from the genus Laurencia. Laurencia dendroidea alone has yielded more than 40 unique terpenoids, supported by 21 identified terpene synthase genes. Green algae contribute sulfated polysaccharides known as ulvans, alongside specialised peptides with emerging biomedical relevance.

The antimicrobial mechanisms underlying these compounds are mechanistically distinct from those of classical antibiotics, which is precisely what makes them attractive in an era of multidrug resistance. Phlorotannins act through a combination of membrane disruption, chelation of essential metal ions and the generation of oxidative stress, while simultaneously interfering with quorum sensing—the chemical communication system bacteria use to coordinate virulence factor production and biofilm formation. Studies of phlorotannins from Hizikia fusiforme, for example, demonstrated both antimicrobial and anti-quorum-sensing activity. Halogenated terpenoids from Laurencia species show potent activity against Staphylococcus aureus and Vibrio species, an effect attributed to their lipophilic and electrophilic chemical character. Sulfated polysaccharides such as carrageenan and fucoidan take a different tack, interfering with bacterial adhesion and colonisation by altering electrostatic interactions at the microbial cell surface. Because these molecules hit multiple cellular targets at once, the risk of resistance emergence may be inherently lower than for single-target drugs.

The antiviral and antifungal records of these metabolites are equally striking. Sulfated polysaccharides including carrageenans and agars can mimic host cell receptors, preventing enveloped viruses from attaching to and entering target cells, while phlorotannins inhibit viral proteases and polymerases by binding to key viral proteins; a phlorotannin-rich extract of Ascophyllum nodosum has been shown to inhibit influenza infection. Against fungi, phlorotannins compromise cell wall integrity and block ergosterol biosynthesis—pathways reminiscent of synthetic antifungals but potentially less prone to resistance—while elatol exerts fungicidal effects through membrane disruption and oxidative stress. Antiparasitic activity has been traced to fatty acid derivatives and phenolic compounds that interfere with parasite metabolism and membrane stability. The review notes, however, that most of this evidence remains in vitro, and that in vivo validation in relevant animal models is urgently needed before clinical deployment.

Beyond direct pathogen killing, the most transformative dimension of the review concerns microbiome engineering. Seaweed-derived polysaccharides such as fucoidans, laminarins and ulvans act as selective prebiotics, enriching beneficial taxa such as Bifidobacterium, Lactobacillus and Akkermansia while suppressing opportunistic members of the Bacteroidetes and Proteobacteria. In broiler chickens, dietary inclusion of 5 to 10 grams per kilogram of seaweed polysaccharides improved intestinal architecture, microbial balance and weight gain in a dose-dependent manner. In pre-weaning Holstein calves, seaweed polysaccharide supplementation increased the abundance of Prevotella and Succiniclasticum, reduced diarrhoea incidence, lowered systemic inflammatory markers including IL-18, TNF-α and IFN-γ, and elevated immune effectors such as complement C3 and IgM. These effects were linked to increased abundance of gut microbes involved in alkaloid and glucocorticoid biosynthesis, suggesting a coordinated immunometabolic mechanism.

The ecological sophistication of these interactions extends to the seaweeds themselves, which the authors describe as holobionts—integrated units of alga plus microbiota. Macroalgae such as Agarophyton vermiculophyllum engage in what researchers call chemically mediated microbial gardening, dynamically attracting symbiotic microbes and excluding pathogens depending on environmental conditions like salinity. Exometabolomic analyses show that macroalgae release distinctive nitrogenous and lipid-rich compounds that support microbial colonisation and nutrient cycling, and genomic surveys have identified more than 4,400 polysaccharide utilisation loci and roughly 8,800 biosynthetic gene clusters in algae-associated bacteria—clear evidence of co-evolutionary adaptation for metabolising algal substrates. Many metabolites previously credited to seaweeds are in fact synthesised or chemically modified by their associated microbiota, a realisation that reshapes how such compounds should be discovered, sourced and standardised.

Biotechnology is now converging to solve the longstanding problems that have kept these compounds out of the clinic. On the extraction side, green technologies—ultrasound-assisted extraction, microwave-assisted extraction, supercritical fluid extraction and enzymatic hydrolysis—are replacing crude solvent methods, improving yield, selectivity and sustainability. Natural deep eutectic solvents optimised for Fucus vesiculosus have delivered high-purity phlorotannins validated by HPLC-MS profiling. Nanotechnology offers solutions to the chronic bioavailability problem: red seaweed-derived nanoparticles provide biocompatibility and controlled release, while silver-based metal–organic frameworks embedded in κ-carrageenan hydrogels combine antibacterial action with the mechanical properties needed for wound dressings. One carrageenan–silver hydrogel composite has already entered commercial wound-healing use, and fucoidan–chitosan nanoparticles are in Phase I trials for targeted colorectal delivery of curcumin.

Synthetic biology is arguably the most ambitious frontier. Metagenomic mining of seaweed microbiota has illuminated vast biosynthetic potential in genera such as Pseudoalteromonas and Vibrio, and CRISPR-based editing combined with heterologous expression in fast-growing chassis like Vibrio natriegens is enabling high-yield biosynthesis of halogenated meroterpenes. The red algal lectin Griffithsin, produced by expression in Nicotiana benthamiana plants, has achieved preclinical validation as a topical antiviral microbicide, demonstrating industrial scalability. Bioinformatic platforms such as antiSMASH and BiG-SCAPE are accelerating the annotation of novel gene clusters encoding alkaloids, terpenoids and glycosides. On the regulatory side, the strongest proof of concept remains sodium oligomannate (GV-971), an oligosaccharide derived from marine algae that received conditional approval in China for Alzheimer’s disease following a 36-week Phase 3 trial—although the review stresses that broader global endorsement awaits more extensive chronic toxicity data.

The authors are candid about the obstacles that remain. Metabolite composition varies with season, geography, salinity, light and harvest conditions; the antimicrobial activity of Ulva lactuca extracts, remarkably, fluctuates with lunar phase at harvest. Poor oral bioavailability, low gastrointestinal stability, first-pass hepatic metabolism and batch-to-batch inconsistency in crude extracts complicate pharmacokinetic modelling and regulatory approval. Structural heterogeneity in fucoidans—where sulfation patterns and molecular weight determine bioactivity—means that harmonised analytical standards are lacking. The review calls for omics-guided bioactivity mapping, standardised extraction and assay protocols, microbiome-informed therapeutic design, and sustainable cultivation systems including land-based aquaculture and integrated multi-trophic approaches that recycle nutrients by pairing seaweed farming with fish or shellfish production. Photobioreactors and controlled tank cultures, in which salinity, light and nutrient stress can be tuned to boost production of phlorotannins, fucoidan and terpenoids, offer a path to reproducible, quality-controlled biomass.

Taken together, the evidence assembled in this review paints seaweed-derived secondary metabolites as far more than a curiosity of marine natural product chemistry. They are multimodal antimicrobials capable of attacking pathogens through mechanisms that bypass existing resistance determinants; they are prebiotic scaffolds that can rebuild dysbiotic microbial communities and dampen inflammation; and they are scaffolds for nanocarriers and synthetic biology platforms that are already reaching commercial and clinical milestones. What is needed now, the authors conclude, is interdisciplinary alignment—marine biotechnologists, pharmacologists, microbial ecologists and clinicians working within shared analytical frameworks—to convert a chemically extraordinary ocean resource into dependable, evidence-based medicines for the microbiome-centred era of healthcare.

The timing of this review reflects a broader shift in how antimicrobial research is conceptualised. Rather than seeking single molecules that sterilise microbial communities, the microecological approach emphasises selective modulation—suppressing pathogens while preserving or even enriching commensal taxa. Seaweed metabolites are unusually well suited to this paradigm because their activities span both direct antimicrobial action and substrate-level nutrition of beneficial bacteria, a dual function rarely seen in conventional small-molecule antibiotics.

The taxonomic partitioning of metabolite classes among algal phyla is itself scientifically informative. The distinct biosynthetic capabilities of Phaeophyceae, Rhodophyta and Chlorophyta mean that sourcing decisions can be guided by target compound class: phlorotannins from brown algae for antioxidant and anti-quorum-sensing applications, carrageenans and halogenated terpenoids from red algae for antiviral and antibacterial purposes, and ulvans from green algae for prebiotic formulations. This phylum-specific specialisation, catalogued in resources such as the Seaweed Metabolite Database, provides a rational framework for bioprospecting programmes.

The open-access status of the review, published as volume 3, article number 7 of Discover Biotechnology, makes the full catalogue of compound classes, mechanisms and translational case studies freely available to researchers in regions where seaweed cultivation is already an established industry. The authors’ citation record, with the article already accumulating citations and thousands of accesses within weeks of publication, suggests substantial interest in microbiome-centred alternatives to conventional antibiotics. As regulatory agencies increasingly grapple with how to evaluate complex, heterogeneous natural products, the standardisation agenda outlined by Annamalai and Kolandhasamy may prove as consequential as the molecules themselves.

Subject of Research: Bioactive secondary metabolites from marine macroalgae for antimicrobial action and microbiome modulation

Article Title: Marine macroalgal metabolites in microbial modulation for next-generation microecological therapeutics

Article References: Annamalai, A., & Kolandhasamy, P. (2026). Marine macroalgal metabolites in microbial modulation for next-generation microecological therapeutics. Discover Biotechnology, 3(1), Article 7. https://doi.org/10.1007/s44340-025-00047-6

Image Credits: AI Generated

DOI: 10.1007/s44340-025-00047-6

Keywords: marine macroalgae, seaweed metabolites, antimicrobial resistance, phlorotannins, sulfated polysaccharides, fucoidan, carrageenan, microbiome modulation, prebiotics, synthetic biology, nanocarriers, microecological therapeutics