 |
| Through the actions of the enzymes COX-2 and
5-LOX, dangerous pro-inflammatory eicosanoids
are formed that damage joint linings. |
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Dual Inflammatory Pathway Blockade
Stimulation of TNF-alpha and IL-1 beta is not the only problem
associated with COX-2 inhibitors. The body has two inflammatory
pathways, both branching from the inflammatory precursor arachidonic
acid. Blocking one pathway while leaving the other wide open is
as imbalancing as it is incomplete. Pharmaceutical companies understand
this shortcoming, and are developing drugs that block both branches
of the inflammatory pathway.[16]
The problem with these drug candidates is that they block both
forms of COX (COX-1 and COX-2) in addition to 5-LOX. Research
has shown that indiscriminate COX inhibitors create a persistent
“rebound effect” on proinflammatory signaling. Even
two weeks after discontinuation of daily aspirin or ibuprofen,
cytokine-stimulated production of TNF-alpha and IL-1 beta was
increased from 270% to 538%.[17]
Thus indiscriminate inhibitors of COX cause the same end result
discussed above—potentiation of the two pivotal cytokines
responsible for cartilage destruction and the inflammatory cascade
in arthritis.
The balanced approach we have discussed—selective inhibition
of COX-2 combined with inhibition of TNF-alpha and IL-1 beta—is,
however, still incomplete. It is necessary to block the second
inflammatory pathway, 5-lipoxygenase (5-LOX), which produces proinflammatory
leukotrienes. Fortunately, an herbal inhibitor of 5-LOX has been
discovered. 5-Loxin™ is derived from Boswellia serrata,
a tree native to India whose aromatic gum resins have been used
by practitioners of the Ayurvedic system of medicine to treat
arthritis for centuries.
Laboratory analysis of the gummy resin from Boswellia shows that
one component, ß-boswellic acid, acts as a specific inhibitor
of 5-LOX.[18]
Having isolated and concentrated the most active of the Boswellic
acids, it is now possible to derive the benefits of 5-LOX inhibition
without consuming large amounts of ordinary Boswellia serrata
extracts.
A drug candidate under development by Shionogi, a Japanese pharmaceutical
company, illustrates the potential of dual inflammatory pathway
blockade. S-2474 is a dual inhibitor of COX-2 and 5-LOX. Not surprisingly,
S-2474 significantly inhibited experimentally induced edema and
arthritis while suppressing inflammatory mediators, all without
ulcerogenic effects.[19]
Demonstrating the pervasiveness of dual inflammatory pathways
in degenerative processes in the body, S-2474 also protected brain
cells from amyloid beta induced neuronal death. Amyloid beta,
which gives rise to the “senile plaques” characteristic
of Alzheimer’s disease, generates the proinflammatory prostaglandin
D2 that was inhibited by S-2474.[20]
A common herb, ginger root, contains gingerols that also inhibit
both the cyclooxygenase and lipoxygenase pathways, and the production
of prostaglandins, thromboxane and leukotrienes.[21-23]
When COX-2 and 5-LOX inhibitors are used in tandem, inflammatory
leukotrienes and prostaglandins are suppressed equally and balance
is achieved safely.
Rebuilding Joints
Chondroitin and glucosamine sulfates are natural components of
healthy joint tissue, and are readily available as dietary supplements.
They work by supplying the natural raw materials cartilage needs
to repair and rebuild itself, and by suppressing the natural enzymes
that break cartilage down in the first place.
Glucosamine is a naturally occurring substance in the body, synthesized
in the chondrocytes. In osteoarthritis, this synthesis is defective
and insufficient, and supplementation with glucosamine has proven
to be useful. The body uses supplemental glucosamine to synthesize
the proteoglycans and the water-binding glycosaminoglycans (GAGs)
in the cartilage matrix. In addition to providing raw material,
the presence of glucosamine seems to stimulate the chondrocytes
in their production of these substances. Glucosamine also inhibits
certain enzymes that destroy the cartilage, e.g., collagenase
and phospholipase. By blocking pathogenic mechanisms that lead
to articular degeneration, glucosamine delays the progression
of the disease and relieves symptoms even for weeks after termination
of the treatment.[24]
Chondroitin sulfate is a major component of cartilage. It is a
very large molecule, composed of repeated units of glucosamine
sulfate. Like glucosamine, chondroitin sulfate has the ability
to prevent enzymes from dissolving cartilage.
Glucosamine alone or in combination with chondroitin sulfate is
becoming recognized as the treatment of choice for osteoarthritis
in the United States. Its ability to actually repair and improve
joint function in addition to providing pain relief gives it a
significant advantage over conventional treatment. Extensive studies
have proven the ability of these natural tissue components to
stimulate new tissue growth and suppress the enzymes that otherwise
break down cartilage.
A new study analyzed glucosamine and chondroitin clinical trials
for knee osteoarthritis from 1980 through early 2002 through a
sophisticated statistical technique known as “meta-analysis.”
Glucosamine studies demonstrated a highly significant efficacy
on all outcomes, including the WOMAC scale (Western Ontario MacMaster
Univ. Osteoporosis Index) and joint space narrowing. Chondroitin
was found effective on mobility, visual analog scale pain, the
Lequesne Index of severity for osteoarthritis and responding status.[25]
In order to maintain optimal joint health well into your later
years, it’s important to maintain healthy weight and to
exercise regularly. Overtaxed joints and weak muscles are a dangerous
combination. Chondroitin and glucosamine sulfates can safely halt
and reverse structural damage to joints, and promote the building
of healthy new cartilage.
Just as arthritis is not one condition, no single treatment is
likely to yield satisfactory results. A systemic approach targeting
proinflammatory cytokines, the dual inflammatory pathways and
cartilage destruction should more effectively address the multifaceted
nature of the host of conditions that are known as arthritis.
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