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Life Extension Magazine

LE Magazine September 2003
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Quenching the flames of inflammatory brain aging
By Dale Kiefer

The COX-2 inhibitors are easier on the stomach than commonly available over-the-counter NSAID medications, such as aspirin and ibuprofen, which can cause gastric bleeding when taken in high doses. NSAIDs block both COX-2 and its more benevolent cousin, COX-1, which is necessary for stomach lining protection. Thus, compounds that block COX-2 selectively are at least as effective as NSAIDs at relieving inflammation, but are supposedly better tolerated by the body. While the makers of COX-2 inhibiting drugs claim they are safe for the stomach, reports published after the drugs were approved show that they can cause gastric side effects in certain individuals. One reason is that so-called COX-2 inhibitor drugs also suppress some COX-1.

Unlike expensive prescription COX-2 inhibitors, plant-derived Nexrutine® inhibits the gene expression of COX-2 rather than directly inhibiting the enzyme, in effect cutting the problem off at the source, rather than intervening once COX-2 is released. This difference in mechanism of action also explains the rapid onset of Nexrutine®’s anti-inflammatory action. Seventy-nine percent of subjects who used Nexrutine® for two weeks agreed that Nexrutine® helped relieve or avoid the general aches and pains associated with overexertion and physical activity, and there was no evidence of side effects at recommended dosages.14 Although the neurological anti-inflammatory effect of Nexrutine® has not been tested in human subjects under tightly controlled conditions, such human trials have been completed on the COX-2 inhibitor Vioxx®(rofecoxib). Researchers concluded that Vioxx® “significantly prevented [experimentally] induced brain inflammation and cholinergic degeneration.”11

Another trial looked at a different COX-2 inhibitor’s effect on the progression of Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS). Researchers declared: “Evidence provides strong support for the therapeutic use of COX-2 inhibitors in ALS.”13 Inflammation has been implicated in a variety of diseases, and may play a role in everything from heart disease to cancer and Alzheimer’s disease. Leading edge research points to dual inflammatory pathway blockade as the most effective strategy for combating inflammation related degenerative disease. In the next section we turn to the other inflammatory pathway, 5-lipoxygenase (5-LOX).

5-Loxin — Nature’s 5-LOX inhibitor
For thousands of years natives of India, North Africa and the Near East have gathered and traded in herbal products obtained from Boswellia serrata, a tree that yields aromatic gum resins when stripped of its bark. In India practitioners of Ayurvedic medicine have traditionally used extracts from the gummy portion of the tree’s sap to treat symptoms of arthritis, which is, after all, an inflammation of the joints. It was this application that prompted Western scientists to investigate Boswellia’s potential as a treatment for inflammation.

They discovered through rigorous laboratory testing that one component, ß-boswellic acid, acts as a specific inhibitor of a key enzyme involved in the inflammation pathway: 5-lipoxygenase (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.

Evidence is mounting for the effectiveness of such a proactive strategy. Although 5-LOX is only beginning to receive the attention it deserves among medical science researchers, some pioneering work on the nature of this powerful enzyme suggests that levels tend to increase as we age. And it’s becoming clear that 5-LOX may also trigger cell death in the brain.15 “Thus,” say the authors of one study, “the 5-LOX pathway could become a promising target of neuroprotective therapies for the aging brain.”15

The rationale for 5-Loxin’s use is based on clinical research into its benefits. Scientists at the University of British Columbia, for instance, investigated the potential neuroprotective benefits of dual inflammatory pathway blockade. They assessed the effects of both a COX-2-inhibitor and a 5-LOX inhibitor working in concert against brain inflammation. Theirresults speak for themselves: “Combinations of COX and 5-LOX inhibitors were more effective than single inhibitors,” write the researchers. “The data suggest that both COX inhibitors and 5-LOX inhibitors may be neuroprotective… and that combinations of the two might have greater therapeutic potential than single inhibitors of either class.”3

They found that inclusion of a 5-LOX inhibitor actually improved the effectiveness of COX inhibitors. “This synergism between 5-LOX and COX inhibitors indicates that inhibition of 5-LOX could be a promising new way to slow inflammation by reducing production of pro-inflammatory leukotrienes…”3

Thus, 5-Loxin’s ability to synergize with the COX-2 inhibitor Nexrutine® suggests that these supplements should be taken simultaneously for maximum effectiveness through dual inflammatory pathway blokade.

Quercetin— anti-thrombotic, anti-inflammatory flavonoid
We’ve all heard the time-honored adage; ‘An apple a day keeps the doctor away.’ While such a prescription for health may seem simplistic in our modern age of sophisticated medical technology, the presence of beneficial quercetin in apples may be the kernel of truth at the heart of this familiar folk wisdom.

Water-soluble quercetin belongs to a class of plant pigments known as flavonoids, which are often subdivided into isoflavones, anthocyanins, flavones, etc. Quercetin, which is present in varying amounts in vegetables and fruits such as apples, onions and tea, is one of the best-known ­ and best-researched of the flavonoids. Quercetin has demonstrated anti-inflammatory, anti-histamine and potent antioxidant properties. It has been implicated in cancer prevention and the prevention of heart disease. But its most relevant brain-health effect is its anti-coagulant activity.16

In response to stress, blood in the brain becomes more prone to clotting, especially among the aged.17,18 Clotting can cause ischemia or stroke, which is responsible for the majority of cases of vascular dementia. Indeed, new research indicates that a series of barely detectable strokes may contribute to vascular dementia. This assault on the brain’s integrity is known as multi-infarct dementia.19 It stands to reason, then, that a mild anti-coagulant, from a natural source, is likely to improve blood flow and help prevent strokes, by preventing clots from forming.

Phosphatidylserine —nature’s cell membrane stabilizer
Phosphatidylserine (PS) is another weapon in the anti-brain aging arsenal. Sold in Europe and Japan as a regulated drug, where it is often prescribed to combat memory loss and learning deficits, PS is a natural and integral component of every cell membrane. It is available as a nutritional supplement in the United States, and serves as a key component of many brain function-enhancing formulas.

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