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Ancient Herb Suppresses Inflammation

March 2007

With the removal of Vioxx® from the market, and sales of other drugs in this class plummeting, scientists are working overtime to identify natural agents that safely block the underlying factors that give rise to inflammation in the body.

Researchers have focused their microscopes on the herb boswellia, which works to block a lethal pro-inflammatory enzyme called 5-lipoxygenase (5-LOX). Until now, only limited strategies have been available to fight the insidious effects of 5-LOX, a potent contributor to inflammatory processes involved in diseases as diverse as cancer, atherosclerosis, arthritis, inflammatory bowel disease, and asthma.

Boswellia Basics

For thousands of years, folk medicine practitioners have used the herb boswellia (Boswellia serrata) to treat a wide range of conditions that we now know are caused by inflammation. This herbal extract is derived from gum resin secreted by the boswellia tree, part of a family of medicinal plants grown and used in India, Africa, China, and the Middle East.

Fighting Inflammation by Inhibiting LOX Enzymes

In the late 1970s, researchers discovered that boswellia produces notable anti-inflammatory effects that are distinct from those produced by nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin.

NSAIDs quell inflammation primarily by inhibiting the cyclooxygenase-2 (COX-2) enzyme.1 Unfortunately, NSAIDs also block the COX-1 enzyme, which is needed to maintain a healthy stomach lining. While NSAIDs are partially effective in treating pain and inflammation, side effects such as stomach irritation and bleeding, kidney toxicity, and peptic ulcers make them less appealing for long-term use. A primary cause of NSAID toxicity is over-inhibition of the COX-1 enzyme.

The stomach-damaging properties of NSAIDs appeared to be solved in 1999, with the approval of selective COX-2 inhibitors that demonstrated less stomach toxicity than NSAIDs. As early as July 2000, however, Life Extension alerted its members to the risks associated with selective COX-2 inhibitors. Since then, reports about the potentially dangerous cardiac side effects of COX-2 inhibitors2 have led scientists to intensify the search for safer options.

Controlling the Inflammatory Cascade

Unlike NSAIDs, boswellia fights inflammation by blocking pro-inflammatory 5-LOX (5-lipoxygenase). 5-LOX is the first enzyme in the metabolic pathway leading to the synthesis of leukotrienes, which are harmful inflammatory substances that scientists believe may have a direct influence on a number of disease processes. Efforts to develop 5-LOX inhibitors that target asthma and cancer1 suggest that boswellia extract may well have applications in managing these and other disease conditions.

In addition to inhibiting 5-LOX and blocking the biosynthesis of harmful inflammatory leukotrienes,3 boswellic acids decrease the activity of another pro-inflammatory enzyme, HLE (human leukocyte elastase). HLE is associated with rheumatoid arthritis and respiratory illnesses such as pulmonary emphysema, cystic fibrosis, chronic bronchitis, and acute respiratory distress syndrome4—all of which are linked by inflammation. Significantly, both leukotriene levels and HLE release are increased in many inflammatory diseases and allergic reactions. To date, the only anti-inflammatory compounds that have been found to inhibit both HLE and 5-LOX are those derived from boswellia.4

Scientists revealed boswellia’s mechanism of action in a study in 2005. They found that boswellia works in part by altering the expression of tumor necrosis factor-alpha (TNF-a), which plays an important role in inflammation. While the body needs pro-inflammatory cytokines like TNF-a to fight off acute infections, an excess of such cytokines promotes chronic inflammation. Applying boswellia to cells had the selective effect of decreasing the TNF-a-induced expression of cell adhesion and matrix metalloproteinase proteins, biochemicals that are related to harmful endothelial dysfunction, cancer metastasis, arthritis, and other disease processes.5

Potential Uses in Preventing and Managing Cancer

Boswellia shows great promise in the prevention and management of several forms of cancer. Pharmaceutical companies are now testing drugs that inhibit LOX enzymes, for use as potential cancer therapeutics.1

German scientists have demonstrated that boswellia extract is a more potent inhibitor of the enzymes that encourage cancer growth in humans than are certain chemotherapy drugs.6 Based on these positive results with boswellia, the researchers believe that the plant’s extracts may help prevent the development and spread of cancer.

Other researchers have tested boswellia extract against five different types of human leukemia cells and two types of human brain cancer cells. They found that boswellia inhibited the proliferation of these cancerous cells by prompting them to self-destruct. Stronger potencies of boswellia were more effective in promoting cancer cell death, thus demonstrating a dose-dependent effect. The Swiss researchers conducting this trial suggested that boswellia may be able to prevent or treat these cancers.7

Scientists from the Cleveland Clinic found that an extract of boswellia was effective against human meningioma cells, which are typically benign tumors of the brain’s covering. Boswellia worked by decreasing the cells’ ability to spread and by killing the tumor cells.8

Boswellia has also attracted the attention of prostate cancer researchers. Prostate cancer cells sampled from men with the disease display an abundance of the 5-LOX enzyme.9 Other research has found that agents that inhibit the 5-LOX enzyme kill human prostate cancer cells,10 suggesting that 5-LOX inhibitors such as boswellia may have applications in preventing or arresting the growth of prostate cancer.9,10

Boswellia extracts also demonstrate promise in fighting melanoma, the deadliest form of skin cancer. Using advanced microscopy and cell-tracking techniques, scientists were able to observe how boswellia extracts caused melanoma cells to differentiate in a healthy way and to adopt cell-growth patterns resembling those of normal cells, while becoming less able to metastasize. Using these techniques, they also observed that boswellia caused fibrosarcoma (connective tissue cancer) cells to lose their ability to metastasize, and then induced cellular suicide (apoptosis) in these same cells.11 At this point, there is enough evidence to encourage researchers to continue looking for therapeutic treatment options utilizing boswellia in some of the most serious diseases.

Reducing Inflammation to Lower Atherosclerosis Risk

Inflammation is an important contributor to atherosclerosis and the development of heart disease. Using boswellia to inhibit the 5-LOX enzymes and reduce inflammation may prove to be an important element in preventing and treating atherosclerosis.

Genetic research recently revealed an intriguing correlation between 5-LOX and atherosclerosis. Scientists discovered that mice with a genetic defect that resulted in their having only one copy of the 5-LOX gene (rather than the usual two copies) were completely protected from developing atherosclerosis.12

Researchers believe that 5-LOX contributes to atherosclerosis in several ways. As noted earlier, increases in the 5-LOX enzyme result in excess leukotriene products that chemically attract white blood cells to adhere to the arterial walls. Furthermore, leukotrienes may promote vascular permeability and low-density lipoprotein (LDL) oxidation. These combined effects may promote the development of atherosclerotic plaques in the arteries, a known risk factor for heart attacks.12

Using boswellia extract to inhibit 5-LOX-induced leukotriene production could thus represent an effective strategy to prevent or treat atherosclerosis.12