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Inhibition of matrix metalloproteinases
A new skin care frontier
What is the best way to keep a vital resource plentiful? Is it to produce more of it or to conserve the existing stock? You would think I am talking about oil supply or grain crop. Yet, I am talking about the skin, or, more precisely the skin matrix. Skin matrix is what would remain if one were to remove all cells from the skin. It is a framework that holds the skin together and consists mainly of intermeshed polymers such as collagen and elastin.
The skin matrix is responsible for the skin's mechanical properties, including firmness, strength, suppleness and elasticity. To a large degree, the signs of skin aging reflect the condition of the skin matrix - the weaker and less regular the matrix, the more wrinkles, roughness and sag one tends to have.
Indeed, the skin matrix is a precious resource, which, just like oil or food, is both produced and consumed. On one hand, skin matrix is continuously synthesized by fibroblasts. On the other hand, whenever it is damaged, malformed or worn out, skin matrix is broken down by the enzymes called matrix metalloproteinases (MMP) and then recycled. But chopping up key matrix proteins, such as collagen and elastin, MMP enzymes play an underappreciated yet critical role in skin physiology.
In a healthy, youthful skin, the synthesis and degradation of the matrix are in balance: damaged or redundant matrix is degraded while the deficit is replenished by the ongoing syhthesis. Unfortunately, this intricate balance gets disrupted as we age: too little of the matrix is synthesized and too much is degraded. As with any supply-demand imbalance, it can be improved by either increasing supply (boosting synthesis of the matrix) or reducing demand (inhibiting the breakdown).
Many of the well-known skin rejuvenation treatments are aimed at replenishing skin matrix by stimulating the synthesis of collagen or elastin (e.g. ascorbic acid, copper peptides, palmitoyl pentapeptide, topical estrogens and other anti-aging treatments). Unfortunately, this approach fails or falls short in some people, presumably due to individual variations in skin chemistry. Besides, the ability to respond to matrix synthesis boosters is known to decline with age.
What's a girl (or a boy) to do, if matrix synthesis boosters have failed her? If you can't produce enough -- conserve! Try to reverse or reduce the loss of skin matrix by inhibiting or reducing the levels of MMP enzymes. This may especially benefit older individuals since research indicates that MMP levels rise excessively with age. It makes a good sense to try to return MMP levels to normal youthful levels, which are sufficient to remove the damaged matrix but allow you to preserve the healthy one.
But what can be done to inhibit MMP enzymes? Unfortunately, the development of practically useful MMP inhibitors by drug companies has met with only limited success so far. As of the time of this writing, the only MMP inhibitor available as a drug is doxycycline hyclate (Periostat), a compound that inhibits MMP-1 (a.k.a. type I collagenase). The approved use of doxycycline hyclate is periodontal disease, where it helps strengthen connective matrix in the gums. Theoretically, it may help to treat wrinkles if used topically, but studies are needed to determine safety and efficacy of such use.
If MMP inhibitor drugs are not ready, what else can be done to reduce skin matrix degradation? Here's some steps to consider:
Reduce or eliminate exposure to environmental factors that stimulate the synthesis of MMP. This includes sunlight (UVA and UVB), chlorinated water, smoking and anything that causes irritation, inflammation and production of free radicals.
Use skin care ingredients with anti-inflammatory activity. Research shows that inflammation increases the levels of MMP enzymes whereas anti-inflammatory agents have the opposite effect. In particular, two different classes of anti-inflammatory agents, so-called COX inhibitors and 5-LOX inhibitors, have been shown to reduce MMP activity. (COX, a.k.a cyclooxygenase, and 5-LOX, a.k.a. 5-lypooxygenase, are the key enzymes involved in the development if inflammatory response.)
Unfortunately, there is not enough data to determine which, if any, of the numerous COX and 5-LOX inhibitors are best for topical use against skin matrix degradation. One possible candidate is boswellic acid, a natural 5-LOX inhibitor found in Boswellia serrata tree. Boswellia serrata extracts are being used by a number of skin care companies in anti-wrinkles products. Whether these companies rely on their proprietary unpublished studies or educated guesses remains unclear.
Another candidate is resveratol, a natural compound found in grapes, known to have a variety of beneficial effects, including antioxidant and anti-inflammatory activity (resveratol inhibits COX and possibly other mediators of inflammation). Skin care products with resveratol are relatively common although I am not aware of any published studies investigating its effect on wrinkles and skin aging.
Finally, lipoic acid, a conditionally essential nutrient, appears to have some anti-inflammatory activity and thus might help indirectly inhibit MMP. In fact, there is some evidence that topical lipoic acid might have anti-wrinkle effects.
Consider botanicals shown to inhibit MMP enzymes. Some plant extracts have been shown to inhibit MMP enzymes, either in test tube (in vitro) or when used treat certain conditions. For example, extracts from Butcher's broom rhizome (Ruscus aculeatus) were shown to inhibit elastase (the MMP that breaks down elastin). This is consistent with its proven beneficial effects on venous insufficiency, a condition linked to varicose veins. It is likely that Butcher's broom's ability to strengthen veins is, at least in part, due to elastase inhibition. We may speculate that applying Butcher's broom extracts topically may firm the skin via the same mechanism. But until studies are conducted, this will remain a hypothesis.
A specially prepared digest of soy protein (a.k.a. soy peptide complex or soy hydrolysate) appears to inhibit some MMP enzymes. Unfortunately, the evidence is preliminary and more research is needed. Soy extracts and hydrolysates have been used in skin care for years. Some soy-based skin care products may, theoretically, inhibit MMP enzymes in the skin. But again, more research is required to confirm that as well as to determine which soy derivatives work best.
The bottom line
There are two main approaches to maintaining and rebuilding skin matrix. One is to stimulate its synthesis, the other is to inhibit its degradation. At present, the agents stimulating the matrix synthesis (particularly collagen boosters) are better researched and supported by clinical evidence. In most cases, it is reasonable to try them first. But sometimes (particularly in older people) they have little or no effect. In that case, one should consider taking steps to minimize matrix degradation by inhibiting or reducing the levels of MMP enzymes. As discussed above, the methods to do that are emerging. Unfortunately, they are still some distance away from the prime time.
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