Life Extension Magazine
Natural Help for Arthritis Sufferers
Dual Inflammatory Pathway Blockade
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%.
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.
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.
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.
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.
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.
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.
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.
1. Feldmann M, et al. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996; 14: 397-440.