The primary target of Laminaran is the Dectin-1 receptor, a C-type lectin receptor expressed mainly on the surface of innate immune cells such as macrophages and dendritic cells. Through specific recognition and binding to Dectin-1, Laminaran can mediate targeted delivery and modulate immune responses. Additionally, Laminaran can regulate the expression of Toll-like receptor 2 (TLR2) in gut-associated lymphoid tissue (GALT). In cholesterol metabolism, Laminaran reduces intestinal cholesterol uptake by downregulating NPC1L1 (Niemann-Pick C1-Like 1) protein expression in intestinal epithelial cells, representing a key mechanism for its lipid-lowering effects.
Laminaran targets immune cells, particularly macrophages and dendritic cells, through pattern recognition receptors such as Dectin-1, complement receptor 3 (CR3), and Toll-like receptors. Upon binding to these receptors, laminaran activates intracellular signaling cascades including Syk, NF-κB, and MAPK pathways, leading to the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12) and enhanced phagocytic and antigen-presenting functions. This immunostimulatory activity contributes to its antitumor effects by promoting Th1 immune responses and activating natural killer cells. Laminaran also has direct effects on tumor cells by inducing apoptosis and inhibiting metastasis.

Laminar polysaccharide (100-800 µg/mL; 24 hours) does not cause any cytotoxicity to human melanoma cells SK-MEL-28 or normal epidermal cells JB6 Cl41. After 24 hours of treatment, the inhibition percentage of viable cell numbers is less than 15% at concentrations as high as 800. The last µg/mL [1]. After 24 and 48 hours of treatment, laminarin (200 µg/mL; 24-72 hours) did not decrease the development of SK-MEL-28 cells; however, after 72 hours of treatment, cell proliferation was reduced by 36%[1]. The phosphorylation of c-Raf (Ser259), ERK1/2 (Tyr202/Tyr204), and MEK1/2 (Ser 221) kinases, as well as total kinases examined protein expression levels, were not affected by low quantities of laminarin (25–50 µg/mL; 24 hours). On the other hand, at 50 µg/mL, p-MEK and p-ERK1/2 will decrease[1].

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In vitro studies have demonstrated that Laminaran possesses多种 biological activities. In Caco-2 cells (human colorectal adenocarcinoma cells), Laminaran inhibits BODIPY-cholesterol uptake in a concentration-dependent manner, with an EC50 of 20.69 μM. Further studies indicate that this effect is associated with downregulation of NPC1L1 protein expression, as siRNA-mediated knockdown of NPC1L1 attenuates Laminaran's inhibitory effect on cholesterol uptake. In macrophage targeting studies, Laminaran, as a coating material for nanoscale delivery systems, protects miRNA-223 from nuclease degradation and is selectively taken up by macrophages via Dectin-1 receptor-mediated endocytosis. Furthermore, Laminaran exhibits anti-inflammatory, antioxidant, and antitumor activities in vitro.
In vitro, laminaran exhibits potent immunomodulatory activity in cultured macrophages and dendritic cells. At concentrations of 10-100 μg/mL, it stimulates the production of nitric oxide and inflammatory cytokines in a dose-dependent manner. It enhances the phagocytic capacity of macrophages and increases the expression of co-stimulatory molecules (CD80, CD86). Laminaran also shows antioxidant activity by scavenging DPPH and hydroxyl radicals, reducing lipid peroxidation, and upregulating antioxidant enzymes such as superoxide dismutase and catalase. In cancer cell lines, laminaran inhibits proliferation and induces apoptosis, with IC50 values typically ranging from 50 to 500 μg/mL depending on the cell type.

When compared to mice treated with PBS, OVA, and laminarin alone, the combination of laminarin (iv; 12.5, 25, and 50 mg/kg; 21 days) with OVA (50 μg) dramatically decreased tumor mass [3].

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In vivo animal models have demonstrated that Laminaran exhibits multiple pharmacological activities. In a mouse model of colitis, oral administration of Laminaran-coated miRNA-223 nanogene delivery system targets macrophages in inflamed colonic regions, promotes M1-to-M2 polarization, and alleviates intestinal inflammation while improving disease outcomes. In high-fat diet (HFD)-fed mice, Laminaran significantly reduces serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, while decreasing hepatic lipid accumulation and promoting fecal cholesterol excretion. Laminaran also ameliorates local villous damage in the jejunum of HFD-fed mice. In normal mice, gavage administration of Laminaran (1-5 mg/mouse for 14 days) increases CD3, CD19, and Mac-3 positive cell populations, reduces lactate dehydrogenase (LDH) levels, and elevates glutamic pyruvic transaminase (GPT) levels. Furthermore, oral Laminaran administration enhances resistance to Staphylococcus aureus and Candida albicans infection in mice.
In vivo, laminaran has demonstrated antitumor and immunomodulatory effects in various animal models. In mice bearing sarcoma or hepatoma xenografts, intraperitoneal administration of laminaran (10-50 mg/kg/day) significantly inhibited tumor growth and increased survival. It also enhanced the efficacy of chemotherapeutic agents when used in combination. In models of bacterial or viral infection, laminaran pretreatment reduced pathogen load and improved survival by boosting innate immunity. Additionally, laminaran has been shown to attenuate allergic inflammation in asthma models and to protect against chemical-induced liver injury via its antioxidant properties. However, its oral bioavailability is poor, so most studies use parenteral routes.

Cell-free in vitro assays for Laminaran receptor binding commonly employ surface plasmon resonance (SPR) technology to evaluate binding affinity to the Dectin-1 receptor. The procedure is as follows: Immobilize recombinant Dectin-1 receptor protein on an SPR sensor chip. Inject different concentrations of Laminaran (e.g., 0.1-1000 μg/mL) diluted in running buffer (such as HBS-EP containing 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.005% Tween-20, pH 7.4) at an appropriate flow rate (e.g., 30 μL/min) with a 2-3 min association time and 5-10 min dissociation time. Record association and dissociation curves using a Biacore instrument to calculate binding constants (KD) and kinetic parameters. Alternatively, enzyme-linked immunosorbent assay (ELISA) can be used: coat microplates with Laminaran, incubate with Dectin-1-Fc fusion protein, and detect binding signals using HRP-labeled anti-Fc antibodies.
Laminaran is not a small molecule drug, so conventional enzyme/receptor binding assays are not applicable. However, its binding to Dectin-1 can be assessed using surface plasmon resonance (SPR) or enzyme-linked immunosorbent assay (ELISA) with immobilized receptor. A competitive binding assay using fluorescently labeled laminaran can be used to determine its affinity for CR3 or Dectin-1. The activation of downstream signaling can be measured by Western blotting for phosphorylated Syk, ERK, and p38 in treated macrophages. Cytokine production is quantified by ELISA or multiplex assays.

Cell Viability Assay[1]
Cell Types: JB6 Cl41 and SK-MEL-28 Cell
Tested Concentrations: 100, 200, 400 and 800 µg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: No cytotoxicity to normal epidermal cells JB6 Cl41 and human melanoma Cells SK-MEL-28.

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Cell proliferation assay[1]
Cell Types: SK-MEL-28 Cell
Tested Concentrations: 200 µg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: diminished cell proliferation at 72 hrs (hours).

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Western Blot Analysis[1]
Cell Types: SK-MEL-28 Cell
Tested Concentrations: 25 µg/mL; 50 µg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Inhibition of phosphorylation of c-Raf, MEK1/2 and ERK1/2 kinases.

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In vitro cellular assays commonly employ macrophage cell lines (e.g., RAW 264.7, THP-1-differentiated macrophages) or intestinal epithelial cell lines (e.g., Caco-2). For cholesterol uptake assays: seed Caco-2 cells in 96-well plates or confocal culture dishes and culture to confluence. Pre-treat with different concentrations of Laminaran (e.g., 0-100 μM) for 1-2 hours, followed by incubation with BODIPY-labeled cholesterol (2.5 μM) for an additional 2 hours. Wash cells three times with pre-chilled PBS, then quantify intracellular fluorescence using a fluorescence microplate reader (excitation 488 nm, emission 525 nm) or observe cholesterol uptake via confocal microscopy. Use NPC1L1 siRNA knockdown experiments to verify target specificity. For immunomodulatory studies, incubate Laminaran nanoformulations with macrophages, then assess uptake efficiency by flow cytometry and measure cytokine expression by qRT-PCR.
In vitro cellular assays for laminaran are performed using primary murine or human macrophages, bone marrow-derived dendritic cells, or RAW 264.7 macrophage cell lines. Cells are incubated with laminaran at concentrations ranging from 1 to 200 μg/mL for 6-48 hours. Cell viability is assessed by MTT or LDH release to ensure non-cytotoxic doses. Nitric oxide production is measured by the Griess reaction, and cytokine levels in culture supernatants are determined by ELISA. Phagocytosis is evaluated using fluorescent latex beads or FITC-labeled E. coli. The expression of surface markers (MHC-II, CD80, CD86) is analyzed by flow cytometry. For antitumor assays, cancer cells are co-cultured with laminaran-treated immune cells or treated directly.

Animal/Disease Models: C57BL/6 mice were injected subcutaneously (sc) (sc) with B16-OVA cells [3] Doses: 12.5, 25 and 50 mg/kg; 21-day
Route of Administration: intravenous (iv) (iv)injection
Experimental Results: Prevent B16-OVA tumors by inducing Ag-specific immune responses grow.

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In vivo studies of Laminaran employ various animal models. For pharmacokinetic studies, male Sprague-Dawley rats receive oral Laminaran (1 mg/kg), with blood collected at various time points post-administration (0.5, 1, 2, 4, 6, 8, 12, 24 hours); plasma drug concentrations are determined using specific β-glucan detection methods. In the colitis model, C57BL/6 mice receive dextran sulfate sodium (DSS) in drinking water to induce colitis, followed by oral administration of Laminaran-coated miRNA nanoformulation (every other day); monitor body weight changes, disease activity index (DAI), colon length, and histology scores. In the hyperlipidemia model, C57BL/6J mice are fed a high-fat diet (HFD) with concurrent Laminaran administration (50-200 mg/kg/day, gavage) for 4-8 weeks; measure serum lipids, hepatic lipids, and fecal cholesterol. For immunomodulatory studies, BALB/c mice receive Laminaran by gavage (1, 2.5, 5 mg/mouse for 14 days); collect blood for cell phenotype and biochemical analyses.
In vivo animal experiments for laminaran are typically performed in mouse models of cancer, infection, or inflammation. Male BALB/c or C57BL/6 mice are injected subcutaneously or intraperitoneally with tumor cells, and laminaran is administered by intraperitoneal injection (typically 10-50 mg/kg) daily or every other day for 2-3 weeks. Tumor volume and weight are measured, and splenocytes are harvested for ex vivo analysis of immune cell populations and cytokine secretion. In infection models, mice are challenged with LPS or pathogens, and serum cytokine levels, organ bacterial load, and survival are recorded. Pharmacokinetic studies are limited due to the compound’s macromolecular nature and rapid clearance.

The pharmacokinetic properties of Laminaran have been studied in rats. Following oral administration at a dose of 1 mg/kg, plasma Laminaran concentrations exhibit two peaks between 0.5 and 12 hours, suggesting possible enterohepatic circulation or multiple absorption sites. At 24 hours post-administration, approximately 20 ± 7% of Laminaran remains in the serum. Laminaran is bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells in a Dectin-1-independent manner. The liver does not significantly contribute to plasma Laminaran clearance. Regarding physicochemical properties, Laminaran is a white to light yellow powder, slightly soluble in water, soluble in DMSO when heated, with a specific rotation [α]D of -40° to -50° (C=0.9, H₂O). Its molecular formula is C18H32O16 with a molecular weight of approximately 504 g/mol.
Laminaran is a high-molecular-weight polysaccharide with limited oral absorption. After intravenous or intraperitoneal administration, it is rapidly distributed to the liver, spleen, and lungs, where it is taken up by macrophages and Kupffer cells. The plasma half-life is short (minutes to hours), and the compound is degraded by β-glucanases in the body. Oral bioavailability is negligible, so it is not suitable for oral dosing. In research, it is usually administered parenterally. The compound is stable in aqueous solutions at neutral pH and can be stored at 4°C for extended periods. Its pharmacokinetic profile has not been extensively characterized, as it is primarily used as a biological research tool rather than a therapeutic agent.

Available toxicological studies indicate that Laminaran has a favorable safety profile. According to multiple research sources, Laminaran is described as a non-toxic, biodegradable biopolymer. In product specifications, Laminaran has an RTECS number of OE1523500 and its TSCA status is "Yes" (registered under the US Toxic Substances Control Act). In a 14-day mouse toxicity study, gavage administration of Laminaran (1-5 mg/mouse) did not result in animal death, but dose-dependent decreases in body weight, liver weight, and spleen weight were observed. Notably, Laminaran increased glutamic pyruvic transaminase (GPT) levels while decreasing lactate dehydrogenase (LDH) levels in normal mice, suggesting potential liver-protective rather than hepatotoxic effects. Due to its favorable safety profile, Laminaran is widely used in functional foods. It should be stored in a cool, dry place away from oxidizing agents.
Laminaran is generally recognized as safe at the doses used in experimental studies. Acute toxicity studies in mice have shown no mortality or adverse effects at intraperitoneal doses up to 200 mg/kg. In repeated-dose studies, mild splenomegaly and transient elevations in serum cytokines have been observed, consistent with its immunostimulatory activity. No significant hepatotoxicity, nephrotoxicity, or hematological abnormalities have been reported. However, because it is derived from algae, allergic reactions are possible in susceptible individuals. Its safety for human use has not been established, and it is not approved for clinical applications.

[1]. Laminaran from brown alga Dictyota dichotoma and its sulfated derivative as radioprotectors and radiosensitizers in melanoma therapy.Carbohydr Polym. 2019 Feb 15;206:539-547.

[2]. Laminaran. https://en.wikipedia.org/wiki/Laminarin

[3]. Laminarin promotes anti-cancer immunity by the maturation of dendritic cells.Oncotarget. 2017 Jun 13;8(24):38554-38567.

Chemical Structure: Laminaran consists of a β-(1→3)-D-glucopyranose main chain with β-(1→6) linkages as branches. Based on the reducing end, there are two chain types: M-type (terminating with 1-O-substituted D-mannitol) and G-type (terminating with D-glucose), with ratios varying by algal species and season. Source: Primarily extracted from brown algae of the family Laminariaceae, commonly from Laminaria, Saccharina, and Eisenia species. Physicochemical Properties: White powder; slightly soluble in water, soluble in DMSO when heated; hygroscopic; specific rotation -45° (C=0.9, water). Synonyms: 昆布多糖, 昆布糖, Laminarin. Research Advances: As a natural biomaterial, Laminaran has been utilized for constructing oral nucleic acid drug delivery systems, nanocarriers for photodynamic therapy, and amphiphilic carrier materials with dual pH/redox sensitivity. IEMDC Status: Not listed. Carcinogenicity: According to available databases, Laminaran has not been classified as a carcinogen by the International Agency for Research on Cancer (IARC).
Laminaran is a β-glucan polysaccharide extracted from brown algae and is used as a research tool for studying innate immunity and immunomodulation. It is often used as a reference compound for Dectin-1 agonists and as a positive control in macrophage activation assays. It has also been investigated for its potential as a prebiotic, antioxidant, and adjuvant in vaccines. Despite its promising biological activities, its large molecular weight and poor oral bioavailability limit its development as a drug. However, derivatives and nanoparticles of laminaran are being explored to improve its pharmacokinetic properties. Laminaran is not an approved drug and is available only for research purposes.

C18H32O16

504.43

504.169

9008-22-4

439306

White to off-white solid powder

1.8±0.1 g/cm3

902.8±65.0 °C at 760 mmHg

499.8±34.3 °C

0.0±0.6 mmHg at 25°C

1.673

-6.08

11

16

7

34

641

12

C([C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OC2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)OC3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)O)O)O

DBTMGCOVALSLOR-VPNXCSTESA-N

InChI=1S/C18H32O16/c19-1-4-7(22)10(25)11(26)17(31-4)34-15-9(24)6(3-21)32-18(13(15)28)33-14-8(23)5(2-20)30-16(29)12(14)27/h4-29H,1-3H2/t4-,5-,6-,7-,8-,9-,10+,11-,12-,13-,14+,15+,16?,17?,18?/m1/s1

(3R,4S,5R,6R)-4-[(3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol

beta-1,3-Glucan; Iodus 40; Laminaran

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~16.67 mg/mL

Solubility in Formulation 1: 33.33 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)