The team behind the study suggest that alginates extracted from the stems of the brown algae Lat. Laminaria hyperborean could be modified with sulphate groups to be a potential remedy for chronic joint pain and inflammation associated with arthritis.
Led by ETHZ researcher Marcy Zenobi-Wong, they report that alginate sulfate can significantly reduce oxidative stress, which is a frequent cause of cell damage or even cell death, and the more sulfate groups attached to the alginate molecule, the greater this reduction.
“Current treatments only address the symptoms of joint disease, but not their underlying causes which include oxidative stress and inflammation in cartilage and surrounding tissues,” noted Zenobi-Wong and coilleagues writing in Biomaterials Science.
“Here we show that the natural polysaccharide alginate and particularly its sulfated derivatives have potent anti-oxidant, anti-inflammatory and anti-immunogenic properties in vitro.”
The algal molecules should therefore slow down cartilage degeneration, said the team.
"The hope is that they can even stop this degeneration," commented study co-author and Empa researcher Markus Rottmar.
Insights on arthritis
Arthritis is one of the most-widespread joint diseases. According to the team, around 90% of all people over 65 are affected to varying degrees – however the degenerative disease is also widespread amongst younger people.
The condition is caused when cartilage in the joint, a type of protective layer on bones that ‘lubricates’ the joint, degenerates over time. The result of this degeneration can be extremely painful for sufferers, because inflammatory reactions are associated with cartilage degeneration.
In the later stages of the disease, bones are no longer adequately protected and can directly rub against each other, the authors said.
While arthritis can affect all joints in the body, it is most often associated with the knee joint, hip joint and fingers.
The disease has been considered incurable until now – with current treatment methods, such as anti-inflammatory drugs and painkillers, mainly addressing the symptoms rather than underlying cause of the disease.
‘Encouraging’ results
In their laboratory tests, the team succeeded in identifying a substance with the potential to halt cartilage degeneration in joints.
“Sulfated biopolymers that mimic aspects of the native extracellular environment of cartilage are recently gaining interest as a means to slow the inflammatory events responsible for tissue degeneration,” said the team.
The team chemically modified alginate extracted from brown seaweed with sulfate groups and then added it in dissolved form to cell cultures to examine the reaction of various cell types to the modified polysaccharide.
“We found that these polymers exert a free radical scavenging activity in a sulfation-dependent manner,” revealed the scientists. “In particular, the sulfation degree of substitution of alginate directly correlated with its ability to scavenge superoxide radicals and to chelate metal ions.”
The authors also studied the effect of sulfated alginate on the ability of the immune cell IL-1β to stimulate inflammatory genes in human chondrocytes – finding decreased expression of the pro-inflammatory markers IL-6 and CXCL8, which inversely correlated with the sulfation degree.
Further research
Since the alginate sulfates have so far only been tested in vitro with cell cultures, the team said that much more work is needed.
However, they commented that the ‘encouraging results’ mean research will now continue.
The next stage is to test the substances on animals, they said. If this is also successful, clinical trials could then be conducted on people.
Source: Biomaterials Science
Volume 5, Issue 9, Pages 1756-1765, doi: 10.1039/C7BM00341B
“Anti-oxidant and immune-modulatory properties of sulfated alginate derivatives on human chondrocytes and macrophages”
Authors: Anne Kerschenmeyer, et al