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| 5mg |
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| 10mg |
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| Targets |
D-Dimannuronic acid sodium does not bind to a single specific protein target. Rather, it acts as an immunomodulating polysaccharide, potentially targeting toll-like receptors (TLRs) or other pattern recognition receptors on immune cells. It modulates immune cell function, leading to reduced production of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, IL-1beta) and increased release of anti-inflammatory mediators. Specifically, it can induce the secretion of TNF-alpha in mouse macrophages, indicating an initial immune activation that may shift to immunomodulation. The compound also interacts with mannose receptors and other carbohydrate-binding proteins on antigen-presenting cells, altering NF-kappaB pathway activation and mitigating chronic inflammation.
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| ln Vitro |
D-Dimannuronic acid sodium is a key building block for sulfated polymannuronate-derived oligosaccharides. The dimannuronic acid disaccharide itself has been investigated for its anti-inflammatory and immunosuppressive properties. In vitro, it can induce the secretion of TNF-alpha in mouse macrophages. Studies on alginate oligosaccharides (AOS) more broadly indicate that mannuronic acid-rich oligosaccharides possess anti-inflammatory activity, which may be mediated through reduced expression of pro-inflammatory cytokines and inhibition of the NF-kappaB signaling pathway. The polysaccharide is non-cytotoxic to normal cells at immunomodulatory concentrations.
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| ln Vivo |
In vivo, D-Dimannuronic acid sodium and its higher oligomers (e.g., mannuronic acid trimers, tetramers) have been investigated in animal models of autoimmune diseases. In a clinical study involving patients with rheumatoid arthritis, the related beta-D-mannuronic acid (M2000) derived from sodium alginate produced significant reductions in disease activity scores (DAS28) and serum inflammatory markers (ESR, CRP) after 12 weeks of oral administration, suggesting its potential as a non-steroidal anti-inflammatory drug. In models of experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis), administration of mannuronic acid oligosaccharides reduces disease severity, demyelination, and immune cell infiltration. Studies also indicate efficacy in treating nephrotic syndrome and acute glomerulonephritis, supporting its broad immunomodulatory potential.
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| Enzyme Assay |
The immunomodulatory activity of D-Dimannuronic acid can be evaluated in cell-free systems measuring cytokine production from activated immune cells or in macrophage stimulation assays. For example, a TNF-alpha induction assay in murine macrophages is performed using RAW 264.7 cells, which are cultured in DMEM with 10% FBS. The cells are treated with D-Dimannuronic acid sodium (0.1-1000 ug/mL) for 4-24 hours. In parallel, positive controls are treated with lipopolysaccharide (LPS, 1 ug/mL). Supernatants are collected and analyzed for TNF-alpha, IL-6, and IL-10 by ELISA. The compound can induce a modest and transient increase in TNF-alpha at low doses, but at higher doses, it may suppress LPS-induced TNF-alpha production, indicating a biphasic response and potential immunosuppressive activity. Alternatively, the compound can be tested for direct binding to mannose-binding lectin (MBL) or other carbohydrate-recognition domains using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). For SPR, biotinylated D-Dimannuronic acid is immobilized on a streptavidin sensor chip, and recombinant human mannose-binding lectin is flowed over the chip at concentrations ranging from 1-100 ug/mL. The dissociation constant (Kd) is calculated from the binding curves; typically, Kd is in the high nanomolar to low micromolar range for such carbohydrate-lectin interactions. However, for D-Dimannuronic acid specifically, published Kd values are not well-characterized.
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| Cell Assay |
Cellular studies are performed using primary human peripheral blood mononuclear cells (PBMCs) or cell lines such as RAW 264.7 macrophages, THP-1 monocytes, or BV-2 microglia. For anti-inflammatory assays, cells are seeded in 24-well plates (5 × 10⁵ cells/well) and pre-treated with D-Dimannuronic acid sodium (10-1000 ug/mL) for 1-2 hours. Cells are then stimulated with LPS (1 ug/mL) or another inflammatory stimulus (e.g., interferon-gamma, TNF-alpha) to induce an inflammatory response. After 6-24 hours of co-incubation, culture supernatants are collected for measurement of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8) and anti-inflammatory cytokines (IL-10, TGF-beta) by ELISA. To assess cell viability, an MTT assay is performed on unstimulated cells treated with the compound alone (0-2000 ug/mL for 24-48 h). To study the mechanism, cell lysates are subjected to Western blot analysis with antibodies against phosphorylated NF-kappaB p65, IkappaBalpha, and p38 MAPK. Alternatively, NF-kappaB nuclear translocation is assessed by immunofluorescence or using a NF-kappaB luciferase reporter assay. Flow cytometry can be used to analyze surface expression of costimulatory molecules (CD80, CD86, CD40, MHC class II) on dendritic cells or macrophages after treatment.
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| Animal Protocol |
D-Dimannuronic acid sodium (often as an oligosaccharide mixture or as the purified disaccharide) is administered to mouse models of inflammation or autoimmunity. For the experimental autoimmune encephalomyelitis (EAE) model, female C57BL/6 mice (6-8 weeks, n=10 per group) are immunized subcutaneously with myelin oligodendrocyte glycoprotein (MOG35-55) peptide emulsified in complete Freund's adjuvant (CFA) containing Mycobacterium tuberculosis. Pertussis toxin (200 ng) is administered intraperitoneally on days 0 and 2 post-immunization. D-Dimannuronic acid sodium (or sodium mannuronate oligomers, 10-50 mg/kg) is administered daily by oral gavage (in water) starting on day 0 or day 7 post-immunization (preventive or therapeutic schedule). Clinical scores are recorded daily (0 = normal, 0.5 = partial tail weakness, 1 = limp tail, 2 = hind limb weakness, 3 = hind limb paralysis, 4 = forelimb weakness, 5 = moribund). Disease onset and peak severity are compared between groups. Spinal cords are collected at peak disease for histology (H&E for inflammation, Luxol fast blue for demyelination). For a rheumatoid arthritis model, collagen-induced arthritis (CIA) in DBA/1J mice is used. Mice are immunized with bovine type II collagen emulsified in CFA, followed by a booster injection 21 days later. D-Dimannuronic acid (50-200 mg/kg/day, p.o.) is administered from day 21 for 4-6 weeks. Paw swelling is measured with calipers, and arthritis scores are assigned weekly. The compound significantly reduces paw swelling and arthritis scores compared to vehicle, with a reduction in serum anti-collagen antibodies and pro-inflammatory cytokines. The clinical study of beta-D-mannuronic acid (M2000) in rheumatoid arthritis patients (12-week double-blind placebo-controlled trial) reported significant reductions in DAS28 scores, ESR, CRP, and morning stiffness duration, with good safety profile (no serious adverse events).
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| ADME/Pharmacokinetics |
D-Dimannuronic acid sodium is a water-soluble polysaccharide (Mw ~392 Da for the disaccharide) that is rapidly absorbed after oral administration. Pharmacokinetic studies on the related mannuronic acid trimer or polymer in rodents indicate a short half-life (t½ ~1-2 h) due to rapid renal clearance. The compound does not accumulate in tissues. It is not metabolized by CYP450 enzymes; it is either excreted unchanged in urine or partially depolymerized by gut microbiota. For research formulation, D-Dimannuronic acid sodium is soluble in water and PBS at concentrations up to 100 mg/mL. For in vivo studies, the compound is dissolved in sterile water or 0.9% saline and administered orally (by gavage) or intraperitoneally. The sodium salt form is the preferred salt for research use. No detailed human PK parameters (Cmax, Tmax, AUC, bioavailability) have been published for D-Dimannuronic acid disaccharide specifically. However, the related drug candidate sodium oligomannate (GV-971) is approved in China for Alzheimer's disease and has a reported oral bioavailability of approximately 2-3% in humans, with peak plasma concentrations achieved 2-4 h post-dose. D-Dimannuronic acid likely has low oral bioavailability but may act locally in the gut to produce systemic immunomodulatory effects via the gut-immune axis.
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| Toxicity/Toxicokinetics |
D-Dimannuronic acid sodium is generally considered safe and well-tolerated. In animal studies (rodents), repeated oral administration of D-mannuronic acid oligosaccharides at doses up to 500 mg/kg/day for 28 days produces no significant adverse effects on body weight, food consumption, hematology, blood chemistry (ALT, AST, BUN, creatinine), or histopathology of major organs (liver, kidney, heart, lung, spleen). No genotoxicity or mutagenicity has been reported. In the clinical study of beta-D-mannuronic acid (M2000, a monouronic acid analog) in 40 rheumatoid arthritis patients (12 weeks, 500 mg BID), the treatment was safe and well-tolerated, with no serious adverse events (SAEs), no discontinuations due to adverse effects, and no significant changes in vital signs, liver function tests, or renal function tests compared to placebo. Mild, transient gastrointestinal discomfort (bloating, nausea) was reported in a small number of patients but did not require treatment. The LD50 (oral) in rodents for related mannuronic acid oligomers is >2000 mg/kg, indicating low acute toxicity. Standard laboratory safety precautions (gloves, lab coat, goggles) are recommended when handling the powder. D-Dimannuronic acid sodium is for research use only and not for human consumption except under clinical trial protocols for approved investigational drugs.
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| References |
[1]. Liu H, et, al. Multiple and multivalent interactions of novel anti-AIDS drug candidates, sulfated polymannuronate (SPMG)-derived oligosaccharides, with gp120 and their anti-HIV activities. Glycobiology. 2005 May; 15(5):501-10.
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| Additional Infomation |
D-Dimannuronic acid (sodium) is the disaccharide building block of alginic acid, a natural linear copolymer of (1,4)-linked beta-D-mannuronic acid (M) and alpha-L-guluronic acid (G) residues extracted from brown seaweed (Phaeophyceae). Alginates are widely used in the food and pharmaceutical industries as thickeners, stabilizers, and for wound dressings due to their biocompatibility and ability to form hydrogels in the presence of divalent cations (e.g., Ca2+). D-Dimannuronic acid sodium is formed by depolymerization of alginates using acid hydrolysis or enzymatic digestion (alginate lyases). The disaccharide is used for the synthesis of mannuronic acid-rich oligosaccharides with defined chain lengths. Mannuronic acid-rich oligosaccharides have been studied for their anti-inflammatory, immunomodulatory, antioxidant, anti-tumor, and prebiotic properties. Sodium oligomannate (GV-971), a mixture of sodium oligomannuronic acid (D-mannuronic acid sodium oligomers with degree of polymerization 2-10), has been approved in China for the treatment of mild-to-moderate Alzheimer's disease, with a proposed mechanism of remodeling gut microbiota and reducing neuroinflammation. D-Dimannuronic acid sodium is a key intermediate and standard for research into these bioactivities. This compound is for research use only and not for human therapeutic use outside of approved clinical studies.
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| Molecular Formula |
C12H17NAO13
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| Molecular Weight |
392.25
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| Related CAS # |
D-Tetramannuronic acid;149511-34-2;D-Pentamannuronic acid;183668-50-0;D-Dimannuronic acid;34044-53-6;D-Trimannuronic acid;66754-13-0;D-Hexamannuronic acid;183668-52-2;D-Heptamannuronic acid;862694-97-1;D-Octamannuronic acid;862694-98-2;D-Nonamannuronic acid;862694-99-3
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~125 mg/mL (~318.67 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5494 mL | 12.7470 mL | 25.4939 mL | |
| 5 mM | 0.5099 mL | 2.5494 mL | 5.0988 mL | |
| 10 mM | 0.2549 mL | 1.2747 mL | 2.5494 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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