Identification

Name
Chondroitin sulfate
Accession Number
DB09301  (DB11353, DB11339)
Type
Small Molecule
Groups
Approved, Investigational, Nutraceutical
Description

Chondroitin sulfate is a glycosaminoglycan considered as a symptomatic slow-acting drug for osteoarthritis (SYSADOA).[1] The SYSADOA status suggested a pain relief and increased joint mobility after a relative long regular administration, as well as a long-lasting effect after the end of the treatment. Chondroitin sulfate is composed of alternating 1,3-N-acetyl-β-d-galactosamine and 1,4-β-d-glucuronic acid units which bear 4-O- and/or 6-O-sulfations at the N-acetylgalactosamine units disposed of in specific patterns. Depending on the predominating disaccharide unit, it will present different biological activities.[2] Chondroitin sulfate is sold as an OTC dietary supplement in North America and it is a prescription drug under the EMA in Europe.[4]

Synonyms
  • Chondroitin sulfates
Product Ingredients
IngredientUNIICASInChI Key
Chondroitin sulfate (bovine)6IC1M3OG5Z9007-28-7Not applicable
Chondroitin sulfate (chicken)7VZ9466BABNot AvailableNot applicable
Chondroitin sulfate (porcine)V5E8ELO4W9Not AvailableNot applicable
Chondroitin sulfate (shark)2ZAJ1K50XHNot AvailableNot applicable
Chondroitin sulfate sodium (bovine)8QTV3DTT8W39455-18-0Not applicable
Chondroitin sulfate sodium (chicken)4T078B3Z6VNot AvailableNot applicable
Chondroitin sulfate sodium (porcine)R27OH35FYQNot AvailableNot applicable
Chondroitin sulfate sodium (shark)Q75WVO004LNot AvailableNot applicable
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Medi-flexx Rx Joint Support FormulaChondroitin sulfate (chicken) (400 mg/1) + Dimethyl sulfone (200 mg/1) + Glucosamine sulfate (500 mg/1)TabletOralTwo Hip Consulting, Llc2014-12-052016-04-11Us
Remaxazon External PatchChondroitin sulfate sodium (bovine) (3 g/100g) + Capsaicin (.0285 g/100g) + Glucosamine (5 g/100g) + Lidocaine (4 g/100g)PatchTopicalHome Aide Diganostics, Inc.2015-03-09Not applicableUs
Categories
UNII
Not Available
CAS number
24967-93-9
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Chondroitin sulfate, used with glucosamine, is indicated to alleviate pain and inflammation from primary osteoarthritis.[7] This supplement is reported to improve joint function and slow disease progression.[8] Osteoarthritis is characterized by progressive structural and metabolic changes in joint tissues, mainly cartilage degradation, subchondral bone sclerosis and inflammation of synovial membrane.[4]

Studies have proposed the potential use of chondroitin sulfate as a nutraceutical in dietary supplements.[3]

Associated Conditions
Associated Therapies
Pharmacodynamics

In clinical trials, chondroitin sulfate has been reported a significant pain relief. Some reports have shown no slow in joint damage. The effects of chondroitin sulfate have been very controversial.[8] One of the characteristics of chondroitin is a slow onset of action with a maximal effect attained after several months.[4] Chondroitin sulfate has been reported to have anti-inflammatory properties by reducing the synovitis and prevent proinflammatory cytokine up-regulation in arthritis models.[4]

It is also registered an anabolic effect of chondroitin sulfate in which it induces the synthesis of hyaluronate in synovial cells, it increases type II collagen and proteoglycan synthesis.[4]

Mechanism of action

Chondroitin sulfate functions as a major component of the intricate extracellular matrix. It is proposed that chondroitin sulfate supply can provide new building blocks for the synthesis of new matrix components.[4]

The anti-inflammatory effect of chondroitin sulfate is thought to be caused by the inhibition of the synthesis of inflammatory intermediates such as the inhibition of nitric oxide synthase, COX-2, microsomal prostaglandin synthase 1 and prostaglandin E2. It is reported also an inhibitory activity in the toll-like receptor 4 which will later inhibit inflammatory cytokines, NFkB and MyD88. This activity suggests a modulation of the MAP kinase pathway. On the other hand, some reports have pointed out an induction on the PKC/PI3K/Akt pathway in neuroblastoma.[4]

The anabolic effect of chondroitin sulfate is suggested to be caused by the inhibition of metalloproteinases such as MMP-1, -3 and -13 as well as ADAMTS-4 and -5.[4]

TargetActionsOrganism
UBrain-derived neurotrophic factorNot AvailableHuman
UGlial cell line-derived neurotrophic factorNot AvailableHuman
UVascular endothelial growth factor ANot AvailableHuman
UC-C motif chemokine 2Not AvailableHuman
Absorption

Chondroitin sulfate is absorbed from the gastrointestinal tract.[2] The absorbed portion reaches a ratio of 10% as unchanged chondroitin sulfate and 90% as depolymerized low-molecular-weight derivatives. This absorption depends on the sulfation status. The bioavailability of chondroitin sulfate ranges from 10-20% following oral administration. Reports have shown a consistent accumulation of the compound in joint tissue. The steady-state is attained after 3-4 days and it takes around 3-6 months to obtain the maximal effect.[4]

After intramuscular administration of chondroitin sulfate, the peak plasma level of 3.8 mcg/ml was reached after 90 min. When given orally, the peak plasma concentration of 4.6 mcg/ml was reached after 240 min.[5]

Volume of distribution

After intramuscular administration of chondroitin sulfate, the apparent volume of distribution was 0.40 ml/g. When administered orally, the apparent volume of distribution changed to 0.44ml/g.[5]

Protein binding

Chondroitin sulfate protein binding reports have shown a very low percentage of protein binding of only 0.23% of the total protein.[6]

Metabolism

Chondroitin sulfate is not metabolized by cytochrome P450.[4] Reports have indicated the presence in plasma of mono-, oligo- and polysaccharides with a molecular weight of less of 5 kDa which are derived from the partial digestion of exogenous chondroitin sulfate.[5] The reported degradation of chondroitin sulfate seems to be very complex and led by the formation of smaller digestion derivatives of the original form.[9]

Route of elimination

Chondroitin sulfate is excreted in the urine as intact polymers and as partial degradation products.[2] After intramuscular administration, about 37% of the administered dose is excreted by urine during the first 24 hours as high- and low-molecular-weight derivatives.[5]

Half life

The approximate half-life of chondroitin sulfate and its derivative metabolites is 15 hours.[4] After intramuscular administration of chondroitin sulfate in humans, the elimination half-life of the chondroitin sulfate was of 275 min. When administered orally, the elimination half-life was presented at 310 min.[5]

Clearance
Not Available
Toxicity

Chondroitin sulfate does not present a carcinogenic potential.[7] On tolerability assays, it has been shown to present great safety and good tolerability without significant severe side effects.[4]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetaminophenAcetaminophen may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Chondroitin sulfate which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineChondroitin sulfate may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AmpicillinAmpicillin may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
AuranofinAuranofin may decrease the excretion rate of Chondroitin sulfate which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Monfort J, Pelletier JP, Garcia-Giralt N, Martel-Pelletier J: Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues. Ann Rheum Dis. 2008 Jun;67(6):735-40. Epub 2007 Jul 20. [PubMed:17644553]
  2. da Cunha AL, de Oliveira LG, Maia LF, de Oliveira LF, Michelacci YM, de Aguiar JA: Pharmaceutical grade chondroitin sulfate: Structural analysis and identification of contaminants in different commercial preparations. Carbohydr Polym. 2015 Dec 10;134:300-8. doi: 10.1016/j.carbpol.2015.08.006. Epub 2015 Aug 8. [PubMed:26428128]
  3. Volpi N: Quality of different chondroitin sulfate preparations in relation to their therapeutic activity. J Pharm Pharmacol. 2009 Oct;61(10):1271-80. doi: 10.1211/jpp/61.10.0002. [PubMed:19814858]
  4. Henrotin Y, Mathy M, Sanchez C, Lambert C: Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations. Ther Adv Musculoskelet Dis. 2010 Dec;2(6):335-48. doi: 10.1177/1759720X10383076. [PubMed:22870459]
  5. Ronca G, Conte A: Metabolic fate of partially depolymerized shark chondroitin sulfate in man. Int J Clin Pharmacol Res. 1993;13 Suppl:27-34. [PubMed:7995679]
  6. Saito A, Munakata H: Analysis of plasma proteins that bind to glycosaminoglycans. Biochim Biophys Acta. 2007 Feb;1770(2):241-6. doi: 10.1016/j.bbagen.2006.10.015. Epub 2006 Nov 7. [PubMed:17178194]
  7. Chemical selection summary [Link]
  8. Arthritis foundation [Link]
  9. Metafishnet [Link]
External Links
KEGG Drug
D00080
KEGG Compound
C00607
PubChem Substance
347910430
Wikipedia
Chondroitin_sulfate
ATC Codes
M01AX25 — Chondroitin sulfate
MSDS
Download (143 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2WithdrawnTreatmentCrohn's Disease (CD)1
3Active Not RecruitingTreatmentAnkle (Ligaments); Instability, Familial / Defect of Articular Cartilage / Degenerative Joint Disease of Ankle and/or Foot1
3CompletedTreatmentJoint Diseases / Muskuloskeletal Diseases / Osteoarthritis (OA) / Synovitis1
3CompletedTreatmentKnee Osteoarthritis (Knee OA)2
3CompletedTreatmentOsteoarthritis (OA)1
3Unknown StatusTreatmentKnee Osteoarthritis (Knee OA)1
4CompletedTreatmentJoint Diseases / Muskuloskeletal Diseases / Osteoarthritis (OA) / Psoriasis / Skin Diseases1
4CompletedTreatmentKnee Osteoarthritis (Knee OA)1
4RecruitingTreatmentDry Eye Syndrome (DES)1
4Unknown StatusTreatmentKnee Osteoarthritis (Knee OA)1
4Unknown StatusTreatmentRhizarthrosis1
Not AvailableRecruitingTreatmentInterstitial Cystitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
PatchTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)190-194ºCLipowitz A. and Newton C. Degenerative joint disease and traumatic arthritis.
water solubilitySoluble'MSDS'
pKa1.5-2Chandran P. and Horkay F. (2012). Acta Biomater.
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Neurotrophin trkb receptor binding
Specific Function
During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the m...
Gene Name
BDNF
Uniprot ID
P23560
Uniprot Name
Brain-derived neurotrophic factor
Molecular Weight
27817.72 Da
References
  1. Nandini CD, Mikami T, Ohta M, Itoh N, Akiyama-Nambu F, Sugahara K: Structural and functional characterization of oversulfated chondroitin sulfate/dermatan sulfate hybrid chains from the notochord of hagfish. Neuritogenic and binding activities for growth factors and neurotrophic factors. J Biol Chem. 2004 Dec 3;279(49):50799-809. Epub 2004 Sep 22. [PubMed:15385557]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
Gene Name
GDNF
Uniprot ID
P39905
Uniprot Name
Glial cell line-derived neurotrophic factor
Molecular Weight
23719.85 Da
References
  1. Nandini CD, Mikami T, Ohta M, Itoh N, Akiyama-Nambu F, Sugahara K: Structural and functional characterization of oversulfated chondroitin sulfate/dermatan sulfate hybrid chains from the notochord of hagfish. Neuritogenic and binding activities for growth factors and neurotrophic factors. J Biol Chem. 2004 Dec 3;279(49):50799-809. Epub 2004 Sep 22. [PubMed:15385557]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor receptor binding
Specific Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
Molecular Weight
27042.205 Da
References
  1. Nandini CD, Mikami T, Ohta M, Itoh N, Akiyama-Nambu F, Sugahara K: Structural and functional characterization of oversulfated chondroitin sulfate/dermatan sulfate hybrid chains from the notochord of hagfish. Neuritogenic and binding activities for growth factors and neurotrophic factors. J Biol Chem. 2004 Dec 3;279(49):50799-809. Epub 2004 Sep 22. [PubMed:15385557]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Not Available
Gene Name
CCL2
Uniprot ID
P13500
Uniprot Name
C-C motif chemokine 2
Molecular Weight
11024.87 Da
References
  1. Distler JH, Jungel A, Caretto D, Schulze-Horsel U, Kowal-Bielecka O, Gay RE, Michel BA, Muller-Ladner U, Kalden JR, Gay S, Distler O: Monocyte chemoattractant protein 1 released from glycosaminoglycans mediates its profibrotic effects in systemic sclerosis via the release of interleukin-4 from T cells. Arthritis Rheum. 2006 Jan;54(1):214-25. [PubMed:16385517]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Receptor binding
Specific Function
Plays an important role in the degradation of dermatan and keratan sulfates.
Gene Name
GUSB
Uniprot ID
P08236
Uniprot Name
Beta-glucuronidase
Molecular Weight
74731.46 Da
References
  1. Metafishnet [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
Gene Name
HEXB
Uniprot ID
P07686
Uniprot Name
Beta-hexosaminidase subunit beta
Molecular Weight
63110.745 Da
References
  1. Metafishnet [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Sulfuric ester hydrolase activity
Specific Function
Not Available
Gene Name
GALNS
Uniprot ID
P34059
Uniprot Name
N-acetylgalactosamine-6-sulfatase
Molecular Weight
58025.575 Da
References
  1. Metafishnet [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Required for the lysosomal degradation of heparan sulfate and dermatan sulfate.
Specific Function
Iduronate-2-sulfatase activity
Gene Name
IDS
Uniprot ID
P22304
Uniprot Name
Iduronate 2-sulfatase
Molecular Weight
61872.405 Da
References
  1. Metafishnet [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
L-iduronidase activity
Gene Name
IDUA
Uniprot ID
P35475
Uniprot Name
Alpha-L-iduronidase
Molecular Weight
72669.19 Da
References
  1. Metafishnet [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation (PubMed:19306108). Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium (PubMed:19306108). In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels (By similarity).
Specific Function
Arylsulfatase activity
Gene Name
ARSB
Uniprot ID
P15848
Uniprot Name
Arylsulfatase B
Molecular Weight
59686.71 Da
References
  1. Metafishnet [Link]
7. Glucuronate-2-sulfatase
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Substrate
In enzymology, a glucuronate-2-sulfatase (EC 3.1.6.18) is an enzyme that catalyzes the chemical reaction of cleaving off the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues of chondroitin sulfate, heparin and heparitin sulfate. This enzyme belongs to the family of hydrolases, specifically those acting on sulfuric ester bonds. The systematic name of this enzyme class is polysaccharide-2-O-sulfo-D-glucuronate 2-sulfohydrolase. This enzyme is also called glucurono-2-sulfatase. This enzyme participates in glycosaminoglycan degradation and glycan structures - degradation.
References
  1. Metafishnet [Link]

Drug created on November 11, 2015 12:54 / Updated on September 07, 2018 03:25