| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| Other Sizes |
| Targets |
Glucosamine hydrochloride downregulates hypoxia-inducible factor-1α (HIF-1α) protein expression in YD-8 human tongue cancer cells under normoxic conditions. The mechanism involves interference with the production of citric acid cycle intermediates, as the effect is blunted by exogenous citrate or 2-oxoglutarate [3].
It also inhibits phosphorylation of p70S6K and S6, translation-related proteins, but this is not directly linked to HIF-1α downregulation [3]. It increases phosphorylation of eIF-2α [3]. |
|---|---|
| ln Vitro |
The DPPH antioxidant activity of glucosesamine sulfate (also known as D-glucosamine sulfate) is dose-dependent [2]. A four-hour short-term treatment with glucosamine sulfate can decrease the phosphorylation of translation-related proteins p70S6K and S6 and inhibit HIF-1α at the protein level [3]. In renal cells treated with TGF-β1 and blocked kidneys, glucosesamine sulfate dramatically lowers renal expression of fibronectin, type I collagen, and α-smooth muscle actin [4].
Glucosamine hydrochloride (1–10 mM) for short-term (4 h) treatment selectively downregulates HIF-1α protein expression in a concentration-dependent manner in YD-8 cells, without affecting HIF-1α mRNA, HIF-1β protein, or HIF-1β mRNA levels [3]. Long-term (24 h) treatment with glucosamine hydrochloride (1–10 mM) downregulates both HIF-1α and HIF-1β at protein and mRNA levels in YD-8 cells [3]. Short-term (2 or 4 h) treatment with glucosamine hydrochloride (10 mM) decreases phosphorylation of p70S6K and S6, and increases phosphorylation of eIF-2α in YD-8 cells [3]. The inhibitory effect of short-term glucosamine hydrochloride (10 mM, 4 h) on HIF-1α protein is blocked by the 26S proteasome inhibitor MG132, but not by the lysosomal inhibitor chloroquine [3]. Short-term glucosamine hydrochloride treatment does not alter HIF-1α protein stability, as determined by cycloheximide chase assay [3]. The downregulation of HIF-1α by short-term glucosamine hydrochloride (10 mM, 4 h) is blunted by exogenous supplementation with citrate (1.5 mM) or 2-oxoglutarate (1.5 mM), but not by pyruvate (1.5 mM) or lactate (1.5 mM) [3]. Short-term (4 h) treatment with glucosamine sulfate (10 mM) or N-acetyl glucosamine (10 mM) does not affect HIF-1α protein expression in YD-8 cells [3]. |
| ln Vivo |
Glucosamine hydrochloride (20, 40, or 60 mg/kg/day, intraperitoneal injection) administered daily starting 7 days prior to unilateral ureteral obstruction (UUO) surgery in male C57BL/6 mice significantly reduces renal fibrosis 14 days after UUO. Semiquantitative analysis shows that 40 and 60 mg/kg doses significantly lower fibrosis scores compared to PBS-treated controls [4].
Glucosamine hydrochloride (40 or 60 mg/kg/day) decreases UUO-induced mRNA expression of α-SMA, collagen I, and fibronectin in obstructed kidneys, as measured by RT-PCR and quantitative real-time RT-PCR [4]. Glucosamine hydrochloride (40 or 60 mg/kg/day) reduces UUO-induced protein expression of α-SMA (by immunofluorescence) and fibronectin (by immunohistochemistry) in obstructed kidneys [4]. Glucosamine hydrochloride (40 or 60 mg/kg/day) suppresses UUO-induced Smad3 phosphorylation in obstructed kidneys, as shown by immunohistochemistry [4]. Glucosamine hydrochloride (40 or 60 mg/kg/day) reduces UUO-induced CTGF mRNA expression but does not affect TGF-β1 mRNA or active dimeric TGF-β1 protein levels [4]. |
| Cell Assay |
YD-8 human tongue cancer cells were cultured in RPMI-1640 with 10% FBS. For protein analysis, cells (0.5 × 10⁶ per well in 6-well plates) were treated with glucosamine hydrochloride at indicated concentrations (1, 5, or 10 mM) for 4 or 24 h. Whole cell lysates were prepared using lysis buffer containing protease inhibitors, and protein concentrations were determined by Bradford assay. Western blot analysis was performed with 50 μg protein per sample, separated by 10% SDS-PAGE, transferred to nitrocellulose membranes, and probed with antibodies against HIF-1α, HIF-1β, p-p70S6K, p-S6, p-eIF-2α, and actin [3].
For mRNA analysis, total RNA was isolated using RNAzol-B, and 3 μg of RNA was reverse transcribed. PCR was performed with specific primers for HIF-1α, HIF-1β, and actin. Actin was used as internal control [3]. For HIF-1α stability assay, YD-8 cells were cultured in serum-containing medium for 4 h to induce HIF-1α, then treated with cycloheximide (translation inhibitor) with or without glucosamine hydrochloride (10 mM) for 0.25, 0.5, or 1 h. HIF-1α protein levels were analyzed by Western blot [3]. For pharmacological inhibition studies, cells were treated with MG132 (26S proteasome inhibitor) or chloroquine (lysosomal inhibitor) with or without glucosamine hydrochloride (10 mM) for 4 h, and HIF-1α expression was analyzed by Western blot [3]. For glucose metabolite supplementation, cells were treated with glucosamine hydrochloride (10 mM) in the presence or absence of pyruvate (1.5 mM), lactate (1.5 mM), citrate (1.5 mM), or 2-oxoglutarate (1.5 mM) for 4 h, and HIF-1α expression was analyzed by Western blot [3]. |
| Animal Protocol |
Male C57BL/6 mice (n=5 per group) were used. Unilateral ureteral obstruction (UUO) was performed under anesthesia. Glucosamine hydrochloride was dissolved in PBS and administered via intraperitoneal injection daily at doses of 20, 40, or 60 mg/kg body weight, starting 7 days prior to UUO surgery. Mice were sacrificed 14 days after UUO, and kidney tissues were collected for histological and molecular analyses. Sham-operated mice served as controls [4].
Kidney sections (4 μm) were stained with Masson’s trichrome for fibrosis assessment. Fibrosis was graded semiquantitatively using the Banff criteria (score 0–3) based on the percentage of fibrotic area in the renal cortex [4]. Immunohistochemistry was performed on kidney sections using anti-phospho-Smad3 and anti-fibronectin antibodies [4]. Male C57BL/6 mice (n=5 per group) were used. Unilateral ureteral obstruction (UUO) was performed under anesthesia. Glucosamine hydrochloride was dissolved in PBS and administered via intraperitoneal injection daily at doses of 20, 40, or 60 mg/kg body weight, starting 7 days prior to UUO surgery. Mice were sacrificed 14 days after UUO, and kidney tissues were collected for histological and molecular analyses. Sham-operated mice served as controls [4]. Kidney sections (4 μm) were stained with Masson’s trichrome for fibrosis assessment. Fibrosis was graded semiquantitatively using the Banff criteria (score 0–3) based on the percentage of fibrotic area in the renal cortex [4]. Immunohistochemistry was performed on kidney sections using anti-phospho-Smad3 and anti-fibronectin antibodies [4]. |
| Toxicity/Toxicokinetics |
The authors cite that humans tolerate at least 184 mg/kg/day of glucosamine hydrochloride without documented toxicity or side effects. Large doses of glucosamine supplementation neither cause glucose intolerance nor affect glucose metabolism [4].
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| References |
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| Additional Infomation |
Glucosamine sulfate is an amino sugar (2-amino-2-deoxyglucose) found in cell membranes. Glucosamine sulfate is thought to play a role in cartilage formation and repair. Long-term use of glucosamine sulfate can slow the progression of knee osteoarthritis; the mechanism appears to be related to glucosamine serving as an important substrate for glycosaminoglycans and hyaluronic acid, both essential for the formation of the articular proteoglycan matrix. (NCI04)
See also: Glucosamine sulfate (note moved to). Glucosamine hydrochloride is an amino sugar widely used as a dietary supplement for joint-related diseases such as rheumatoid arthritis and osteoarthritis. It has demonstrated anti-inflammatory activities, including inhibition of COX-2, iNOS, MMPs, and NF-κB. Accumulating evidence also supports anticancer effects, including inhibition of tumor growth and induction of apoptosis in various cancer cell lines (prostate, breast, leukemia, glioma, tongue). The present study reveals a novel mechanism: short-term glucosamine hydrochloride treatment selectively downregulates HIF-1α protein in YD-8 tongue cancer cells by interfering with the production of citric acid cycle intermediates, without affecting global protein synthesis. This effect is specific to the hydrochloride salt, as glucosamine sulfate and N-acetyl glucosamine did not show similar activity [3]. |
| Molecular Formula |
C6H15NO9S
|
|---|---|
| Molecular Weight |
277.24
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| Exact Mass |
277.046
|
| CAS # |
29031-19-4
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| Related CAS # |
Glucosamine;3416-24-8;Glucosamine hydrochloride;66-84-2
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| PubChem CID |
115046
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| Appearance |
White to off-white solid powder
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| Density |
1.563g/cm3
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| Boiling Point |
449.9ºC at 760mmHg
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| Melting Point |
176°C
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| Flash Point |
225.9ºC
|
| Vapour Pressure |
5.53E-10mmHg at 25°C
|
| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
17
|
| Complexity |
223
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
S(=O)(=O)(O[H])O[H].O([H])[C@]([H])([C@@]([H])(C([H])([H])O[H])O[H])[C@@]([H])([C@]([H])(C([H])=O)N([H])[H])O[H]
|
| InChi Key |
FGNPLIQZJCYWLE-BTVCFUMJSA-N
|
| InChi Code |
InChI=1S/C6H13NO5.H2O4S/c7-3(1-8)5(11)6(12)4(10)2-9;1-5(2,3)4/h1,3-6,9-12H,2,7H2;(H2,1,2,3,4)/t3-,4+,5+,6+;/m0./s1
|
| Chemical Name |
(2R,3R,4S,5R)-2-amino-3,4,5,6-tetrahydroxyhexanal;sulfuric acid
|
| Synonyms |
D-Glucosamine sulphateGlucosamine sulphateGevoloxGlucosamine sulfate
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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 (~450.86 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (360.69 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6070 mL | 18.0349 mL | 36.0698 mL | |
| 5 mM | 0.7214 mL | 3.6070 mL | 7.2140 mL | |
| 10 mM | 0.3607 mL | 1.8035 mL | 3.6070 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06200415
Conditions:Periodontal PocketLink: https://clinicaltrials.gov/ct2/show/NCT05237596
Conditions:Erosive Osteoarthritis of the HandLink: https://clinicaltrials.gov/ct2/show/NCT03911570
Conditions:Hand Osteoarthritis
Title:Individual Differences in Glucosamine Sulfate Exposure Levels
Status:Unknown status
updateDate:2017-07-05
Ctid:NCT03201276
Link: https://clinicaltrials.gov/ct2/show/NCT03201276
Conditions:Knee OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT01906801
Conditions:Osteoarthritis|Glucosamine|DiacereinLink: https://clinicaltrials.gov/ct2/show/NCT03106584
Conditions:Knee OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT02858297
Conditions:Oral Lichen PlanusLink: https://clinicaltrials.gov/ct2/show/NCT01074476
Conditions:Knee OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT02167516
Conditions:Knee OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT02214095
Conditions:Chronic PeriodontitisLink: https://clinicaltrials.gov/ct2/show/NCT00860873
Conditions:OsteoarthrosisLink: https://clinicaltrials.gov/ct2/show/NCT00404079
Conditions:Low Back PainLink: https://clinicaltrials.gov/ct2/show/NCT01293305
Conditions:OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT01172249
Conditions:Osteoarthritis, KneeLink: https://clinicaltrials.gov/ct2/show/NCT00513422
Conditions:Osteoarthritis, KneeLink: https://clinicaltrials.gov/ct2/show/NCT00833157
Conditions:Osteoarthritis of the KneeLink: https://clinicaltrials.gov/ct2/show/NCT00317655
Conditions:Back PainLink: https://clinicaltrials.gov/ct2/show/NCT00110474
Conditions:Knee OsteoarthritisLink: https://clinicaltrials.gov/ct2/show/NCT00251069
Conditions:OsteoarthritisProducts are for research use only; We do not sell to patients
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