Current Research Trends: The Search For Natural Anti-Inflammatory and Anti-aging Compounds

Botanical Antioxidants As Anti-Inflammatories

Many laboratories both in academia and in industry are now focusing their research efforts toward identifying botanically derived compounds that display both antioxidant and anti-inflammatory properties, and which may prove to be much safer than the currently used prescription anti-inflammatories such as corticosteroids and biologics. Many well known antioxidants have been shown in recent years to have pronounced effects on the cellular signaling pathways that lead to inflammation. For example, the common antioxidant, Vitamin C, not only stimulates collagen gene activity, but also inhibits UVR induced PGE-2, a potent inflammatory hormone. Vitamin E also blocks PGE-2 production and alters signaling pathways that regulate cell proliferation. Two graphs that show the anti-inflammatory activities of  several well-known antioxidants is shown below.

Note that many antioxidants can block PGE-2 production, which is important given recent evidence that this hormone is linked to skin cancer. Scientists at OU have been studying the biological properties of many natural antioxidants for many years, and in fact, DermaMedics was originally created to continue the Botanical Active discovery research started at The University of Oklahoma Health Sciences Center in 2004. Like researchers at other institutions, scientists in the Department of Biochemistry and Molecular Biology developed a screening program to characterize the biological activities of botanically derived antioxidants, with the goal of finding new and safer ways to address the number one cause of human disease; INFLAMMATION. Such diseases as MS, arthritis, Parkinson's, Lupus, cardiovascular disease, Alzheimer's, most skin diseases, skin aging, and even cancer are all inflammation based. And although there are many drugs used to treat these diseases with varying levels of efficacy, all have some potentially serious side effects as a result of their potency and immunosuppressive effects. Because most pharmaceutical drugs on the market today had their origins in plant derived chemical compounds, research laboratories all over the world are now "going back to nature"  to identify potentially useful compounds that are effective in addressing inflammation but which do not have the side effects of synthetic drugs on the market today. Scientists at OU Medical School have conducted years of research to characterize the biological activities of botanical anti-inflammatories and antioxidants with the goal of making them available for licensing by pharmaceutical companies. That research effort, which is still ongoing, has resulted in the identification of many botanically derived compounds with pronounced antioxidant, anti-inflammatory and anti-aging activities. An example of one compound that has been found to block the production of PGE-2 in skin cells exposed to UV radiation is shown below.

Since PGE-2 is now known to  be involved in the development of skin cancer, identifying natural compounds that can block the production of this compound  may lead to the development of products to prevent sun-induced skin cancer. Several of the discoveries made at the University of Oklahoma have been transferred to DermaMedics and the company is now working with potential licensing partners to commercialize this technology.

 Botanical Antioxidants with Anti-Aging Activities

In addition to carrying out research to assess the anti-inflammatory properties of botanically derived antioxidants, a great deal of research in university laboratories as well as in research labs throughout the skin care industry is focused toward identifying those natural compounds that can help repair aging skin. Perhaps the most widely studied natural antioxidant is Vitamin C, which has been rigorously studied for the past 50 years for its anti-aging properties. Through the use of human skin cell culture models and molecular biology methods, vitamin C has been shown to stimulate collagen gene activity, to reduce the level of inflammatory cytokines, and to inhibit the production of enzymes that damage the skin's dermal matrix. In fact, skin care companies have been built entirely around the use of this compound in topical products. Another natural compound that has been widely studied for its anti-aging effects is the active form of Vitamin A, retinoic acid. Interesting, this compound is the only one to ever receive FDA approval as a prescription drug for the treatment of skin aging. Many skin care products today contain retinol, which is the non-prescripton precursor form of Vitamin A. There are many other natural antioxidants that have now been shown to have anti-aging activities, including ferulic acid and EGCG (epigallocatechin gallate) and research is ongoing to identify more.  

This next section provides an overview of the various strategies used by scientists to identify naturally occurring botanical compounds that may prove useful in future oral and topical products.

 

Step 1. Identification of “Bioactive” Compounds

To rapidly screen hundreds of naturally occurring antioxidants and other compounds for specific anti-inflammatory and/or anti-aging activities, the first step to be completed is to develop a screening program that is both fast and cost-effective. For example, if one is looking for compounds that might have utility for addressing arthritis, one type of specific cytokine array test will be developed, while identifying compounds that might be useful in addressing skin problems will require a dfferent "Bioactive screening array" to be established. For skin specific screening, scientists develop their assays around the use of human skin cell cultures, including keratinocyte, monocyte, fibroblast, and melanocyte cultures.  

Step 2. Formulation Development

As is the case with any development program at any company, identifying a "bioactive" compound from a screening program that shows promise, does not necessarily ensure that it will be effective if developed into an oral or topical formulation. It has been estimated that only 1 out of 5000 compounds initially identified with screening programs, ever makes it successfully through product development and clinical testing. The first step in evaluating the topical efficacy of any compound discovered through the screening program is to develop a formulation that is : 1) is compatible with the "bioactive",  2) doesn't cause the "bioactive's" degradation, 3) contains a concentration of "active" that is high enough to exert the desired biological effects, 4) is fast-absorbing with a non-greasy and non-tacky feeling on the skin, and 5) doesn't produce unwanted side effects. 

Step 3. Topical Formulation Testing For Skin Penetration

After a suitable topical formulation has been developed, it must then be tested to determine: 1) how efficiently it is absorbed into the skin, and 2) how long a single application of product will continue to provide benefits to the skin. To determine these two parameters, formulation chemists test each formulation on human skin using a technique called Percutaneous Absorption Analysis.