Natural products research

How do scientists analyze natural active ingredients to use them in skin care products?

The desire for healthy-looking skin exists for centuries and humans often tried to use plants or any kind of gift from nature in search of help.

Scientists are using the same method, but with the help of the most recent finds in Biotechnology, to proceed to the identification and extraction of active ingredients from a wide range of plants and living creatures.

A new way of identifying and selecting active ingredients has been launched by French researchers in partnership with a Spanish laboratory. They studied a variety of botanical species from Africa and South America in the aim of discovering the active ingredients in those plants and determine whether they could bring new natural ingredients to cosmetics.

Their objective was to find different utilizations for the active compounds, using them as anti-oxidants or anti-inflammatories. Having identified a potentially useful molecule from one of the plants they were studying, the task was to find a complementary molecule from another plant that could be combined with the first one to make the active ingredient in a skincare product. In this way, the active ingredient in a self-tanning cream for example, could be accurately described as an extract of the two plants.

The team managed to determine three main active ingredients and now has patent rights for the use of these active ingredients in the whitening creams and self-tanning products it has developed, as well as an anti-inflammatory ingredient.

Natural Products and Combinatorial Chemistry
New technologies have irrupted in natural products scientific research.

Combinatorial Chemistry generates expectations but also debates within the Scientific and Laboratory communities.

First, what is Combinatorial Chemistry?
Lets have a look at a concrete example. While a Biologist collects leaves from some species, proceeds to their extraction and analysis until getting leaf components to find potential biological properties, a Chemist from a modern laboratory carries out a standard reaction: A + B = C; knowing that now A is actually a mixture of five components while B may be a composite of 10. So instead of a single product C, the Chemist produces a mixture of 50 different compounds! This is Combinatorial Chemistry.

Combinatorial Chemistry has similarities in Nature.
Our immune system is able to produce hundreds of millions of different antibodies by recombining segments of a variable region of primary structure.

South Pacific cone snails have had the capacity to make mixtures for the past 50 million years. These creatures have the ability to harpoon and paralyze their prey using highly effective peptide toxins. The active ingredients are actually mixtures of 100 or more deadly venoms, essentially produced by the combinatorial scrambling of amino acids.

Natural Products and Combinatorial Chemistry
A lot of resources can be wasted while studying Combinatorial Chemistry, producing a lot of molecules that don't work. But, once the similarities between natural product extraction and deliberate mixture production were recognized, the dogma that chemical entities should be synthesized, purified and analyzed one at a time began to erode. The result is quite controversial but very exciting, a challenging new future for the chemical sciences.

And this is why some laboratories are already preparing mixtures as large as 200 billion separate compounds in each product vial.

Controversial, as naturalists say that billions of years of evolution have forged compounds that have unique abilities to act on living things. Drawing from the useful properties of plants, fungi, bacteria, insects, animals, sea creatures, they have purified vital compounds such as digitalis from the foxglove plant, aspirin from the willow tree, penicillin from mold cultures, steroids from animals. Such compounds might never develop if drug research is restricted to robot screening of synthetic libraries.

Critics complain that humanity may wind up the loser, as financial resources and brain power feed the machines. They cite a 2002 study published in the Journal of Natural Products that found, two decades after "combinatorial chemistry technology" had been introduced, it had not produced a single new compound that had won approval as a drug from the U.S. Food and Drug Administration.

Scripps, Pfizer and many other drug manufacturers point out that they have several synthetically discovered drugs in the clinical-trial pipeline now. Pfizer has three of them, Lederer said: torcetrapib, a cholesterol treatment; UK427857, an HIV compound, and CP690550, a medicine that may help prevent transplanted organs from being rejected.

Scripps professor Steve Kay said Scripps' success with synthetic chemistry has not stopped the institute from working with natural compounds. The work on the chemotherapy drug Taxol, originally from a tree, is a good example.

"We really cover the whole spectrum," he said. "You need a balanced approach. You're not ever going to put all of your bets on one horse."

The key is speed
At the Harbor Branch Oceanographic Institution in Fort Pierce, scientists are betting that plants and animals from the sea will produce exciting compounds. One of their discoveries, Discodermolide, is in clinical trials on animals now, and Novartis may try to use it as an anti-cancer drug.

That substance was found in the cells of a sponge, collected from deep within the waters of the Caribbean, said Shirley Pomponi, vice president and director of research for Harbor Branch.

"Nature offers much more interesting molecules than even our computers can come up with," Pomponi said.

A leading critic of the synthetic camp is Samuel Danishefsky, who leads the bioorganic chemistry laboratory at Memorial Sloan-Kettering Cancer Center.

During a Scripps-sponsored conference in Indian Wells, Calif., Danishefsky told Scripps chemists and biologists that their synthetic methods were a "fishing expedition" important, but not nearly as reliable as starting from nature.

"Scripps is on the cutting edge of synthetic chemistry," Danishefsky said. He conceded that Scripps has had some notable discoveries, but said that on the whole, synthetic chemistry "has not been terribly successful. You make the compounds just because you can, and then you test them and hope to turn up things that quote-unquote 'work.' There's a lot of chance involved in what they're doing."

The key word is speed.
"In normal human development, a mysterious cocktail of hormones and growth factors causes cells to develop, and it is hard to mimic those processes outside the body," Wu said. "We are taking a shortcut. We are trying to identify synthetic molecules which can mimic those 'natural' processes."

Wu started by identifying chemicals associated with heart cells, and, with the help of Sheng, used high throughput screening to test 100,000 similar compounds. The robot combines chemical solutions, then drips them into hundreds of test tubes containing reactive animal proteins or cells. If a sought-after reaction develops, the robot identifies the substance as a "hit."

Wu's screen identified 80 potentially useful molecules. Four proved to be most potent. Wu then tested them in gelatin-coated plates, laced with embryonic mouse cells. Then he waited. After one week, about half the cells tested positive for proteins essential to heart muscle contraction. Had he tested those chemicals himself, one at a time, the research would have used up the better part of his career.

"It would have taken 10 years or something without the robot," he said.
Instead, he spent two months developing plans for the robot, one month for the actual screening and another six months to reconfirm the "hits."

The compound Wu made started with a common building block chemical called pyrimidines, modified in several ways.

Those chemicals are already found in cells in their natural form, said Snader. Modifying natural compounds may represent the most successful path for synthetic chemistry, he said.

There are places for both of these fields. It just is important not to abandon natural products and whole animal screening.

BIO SKIN CARE™ - a biological complex of active molecules

BIO SKIN CARE™ is made with a complex proteic substance collected from land snails that nature has endowed with the ability to repair their skin quickly when damaged, and to protect it from environmental hazards and pollution.

Biological and chemical analysis of the mucin has shown to contain:

proteins that enable cells to communicate and effectively coordinate activities between one another (growth factors),

enzymes (proteins that catalyze, or speed up biochemical reactions within skin cells by a factor of many thousands),

copper peptides that signals your system to trigger the renewal of skin cells from within the deep layers of the skin

· glycosaminoglycans (GAGs) - complex carbohydrate chains that are not only vital moisturizers and lubricants present in the interstitial spaces between surface skin cells but by virtue of their interaction with growth factor proteins and their receptors act as regulators of vascularization (cappilary blood vessel formation) and cell division, and are fundamental biological players in the cellcell and cellmatrix interactions that take place during normal and pathological events related to cell recognition, adhesion, migration and growth,

· immune modulating glycoproteins that act as intracellular messenger molecules whose major function is to attract immune cells to sites of infection (chemokines) and as intercellular mediators in the generation of an immune response (cytokines),

antibacterial glycoproteins that get rid of microbes within the skin follicles,

natural anti-inflammatory factors that limit oxidative damage after tissue injury.

Skin healing is a highly ordered systemic process that involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by enzymes and growth factors. The slowing of skin healing that occurs when we age is related to changes in the activity of these various regulatory factors.

Now, for the first time, BIO SKIN CARE™ cream brings you the ONLY skin renewal product that incorporates natural skin renewal activators to gently exfoliate the worn out cells while at the same time triggering the reproduction of new collagen and elastin cells, resulting in a coordinated biological regulation of the skin renewal process and thus advanced skin rejuvenation and reduction/ elimination of skin blemishes

Click: for more about Natural Skin Renewal Activator