The therapeutic effect results
from the complementary effects of the unique combination of
biologically active compounds found in the green-lipped mussel.
Glycosaminoglycans (GAG) Synthesis
GLM Extract contains Glucosamine, Chondroitin sulphate, Hyaluronic
acid and Dermantan Sulphate [1].
GLM Extract is a natural source of glucosamine - not free
glucosamine - a component of joint cartilage and of synovial
fluid that has been shown to slow the structural damage within
arthritic joints[9].
Chondroitin sulphate makes up the basic ground substance
of both, the bone and cartilage and may inhibit catabolic
cytokine initiated degradation of the cartilage [1].
Hyaluronic acid is a nonsulphated GAG found in the proteoglycans
structure and it also contributes to the viscosity of the
synovial fluid [1].

Inhibition of Cytokine Function
Cytokines are chemical messengers produced by cells in response
to a variety of stimuli. Catabolic cytokines present in arthritic
joints perform a number of detrimental functions, which result
in an accelerated breakdown of cartilage and enhanced inflammation.
The catabolic cytokines, Interleukin-1 (IL-1), Interleukin-2
(IL-2) and Tumor Necrosis Factor - alpha (TNF- )
are the ones mainly associated with destructive function in
the arthritic joint due to their influence on neutrophil infiltration,
matrix metalloproteinase and proinflammatory prostaglandin
production.
Studies using arthritic rats have demonstrated the inhibitory
effect of GLM Extract on neutrophil activity [4]
and pro-inflammatory prostaglandin synthesis 8 along with
the inhibition of catabolic cytokine activity at the cellular
level [1].

Selective COX-2 Inhibition
GLM Extract is a selective inhibitor of cyclo-oxygenase type
2. Inhibiting the activity of cycloxygenase enzymes, which
convert cell membrane phospholipids into pro-inflammatory
prostaglandins, is an important anti-inflammatory mechanism.
However, there are two isozymes of cycloxygenase, designated
as COX-1 and COX-2.
The COX-1 isozyme is a constitutional enzyme that has an
important role in maintaining the health and integrity of
the digestive system, kidney function and platelet aggregation
where as, COX-2 isozyme is induced in response to an inflammatory
stimulus. The fact that GLM Extract is able to inhibit COX-2
selectivity without inhibiting COX-1 activity means that the
product does not have any damaging effects on the stomach
and does not adversely affect kidney function or platelet
aggregation.
Recent studies at the University of Otago School of Medicine,
NZ have shown that GLM Extract is a selective COX-2 inhibitor
[5].

5-Lipoxygenase Inhibition
In addition to cyclo-oxygenase inhibitory activity, GLM Extract
has been shown to inhibit 5-Lipoxygenase activity in stimulated
human polymorphonuclear leukocytes in vitro [10].
5-Lipoxygenase activity is similar to cycloxygenase enzymic
activity involving the conversion of endogenous arachidonic
acid to proinflammatory and broncho-constrictive leukotrienes.
These leukotrienes are adversely indicated in arthritic and
asthmatic disorders and inhibition of their function is important
for the control of these disorders.

Apoptosis Reduction
Apoptosis is a term used to describe programmed cell death.
This is a normal physiological function but can become uncontrolled
in some disease states. In arthritis, an elevated level of
apoptosis can occur in the body's white blood cells (T-lymphocytes).
T-lymphocytes have been shown to be important mediators in
the tissue destruction seen in rheumatoid arthritis.
Animal studies have shown that GLM Extract inhibits the accumulation
of T-lymphocytes at inflammatory sites [11].
However, this is still to be proven in the case of human lymphocytes.

Inhibition of Histamine Production
Histamine production is normally associated with allergy
reactions. However, it is also a component of the acute phase
of inflammation and its control is therefore influential in
the symptomatic relief of inflammatory disorders such as arthritis.
Japanese researchers discovered that GLM Extract naturally
contains an active anti-histamine component in the form of
Phospholipid Lysolecithin [6].
Although anti-histamine preparations are not a standard part
of treatment of arthritic diseases, their complementary function
in inhibiting the acute-mediator driven phase of inflammation
is beneficial.

Micronutrients
GLM Extract is prepared from marine mussels, which have naturally
assimilated micronutrients from their sea environment, in
a manner, which retains all the components in a stable and
functional state.
Some minerals such as boron, manganese and copper have influence
as anti-inflammmatory agents either directly or synergistically
with other mediators. Fat-soluble vitamins such as A, D, E
and K are not in excess in GLM Extract and there is no danger
of hypervitaminosis or biosynthesis of excess calcium.

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