Modified Polyphenol Technology

Modified Polyphenol Technology : Changing the Rules of the Game

(The heavy science information including references)

Modified Polyphenol Technology (MPT) relates to polyphenolic compounds, in particular ethoxylated polyphenolic compounds and the use of such compounds in disease prevention, disease treatment and life extension in humans and animals.

The 20th century has been called the "Aspirin Century", displacing salicin, an anti-inflammatory agent extracted from bark of the willow tree. The human body metabolizes the prodrug, salicin, to the aspirin precursor, salicyclic acid. Salicyclic acid was traditionally used sparingly due to its unpleasant taste and tendency to damage the stomach. Hence, doses of the active ingredient were small, rendering it less effective.

The modification of salicyclic acid by reaction with acetic anhydride produces the less irritable acetylsalicylic acid (aspirin). Aspirin is also combined with caffeine and sold as the analgesic Anacin.

Ever since Bayer's aspirin invention (US patent 1900) natural products have been a very distant second to drugs in the treatment and prevention of disease and aging related illness.
Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90 % (de Grey ADNJ, 'Life Span Extension Research and Public Debate: Societal Considerations', Studies in Ethics, Law, and Technology, 2007; 1(1), doi:10.2202/1941-6008.1011).

Arthritis and diseases of affluence such as cancer, obesity and metabolic syndrome, all have inflammation in common. While genetic factors are considered a factor in some instances, environmental factors, in particular our modern diet rich in processed foods seem to carry the heavy burden of blame.

Over the last 20 years, a significant body of evidence has emerged indicating that chemically diverse classes of naturally-occurring substances derived from higher plants are of potential interest for therapeutic interventions in several inflammatory diseases.
Increasingly it is being found that a large range of plant-derived constituents interfere with three relevant targets involved in the inflammatory process, namely arachidonic acid metabolite pathways, nitric oxide and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κΒ). This has expanded their potential therapeutic use in the management of relevant inflammatory related diseases (Calixto JB, Otuki MF and Santos ARS, 'Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor κ B (NF-κΒ)', Planta Med., 2003; 69(11):973-983).

By way of example, many antioxidants found in foods have anti-inflammatory properties, such as those found in tea, coffee, wine and chocolate, yet these anti-inflammatory foods may impact on prolonged inflammation (also referred to as chronic inflammation), but are not potent enough to bring about pain relief in humans. In many instances these antioxidant-rich foods can be consumed in high doses but their bioavailability in humans is poor, hence delivering poor health outcomes.

The family of NF-κΒ transcription factors is intimately involved in the regulation of expression of numerous genes in the setting of the inflammatory response. Since inflammatory processes play a fundamental role in the damage of articular tissues, many in vitro and in vivo studies have examined the contribution of components of the NF-κB signaling pathways to the pathogenesis of various rheumatic diseases, in particular, of osteoarthritis (OA) and rheumatoid arthritis (RA). Inflammation, cartilage degradation, cell proliferation, angiogenesis and pannus formation are processes in which the role of NF-κB is prominent (Roman-Bias JA and Jimenez SA, 'NF-κΒ as a potential therapeutic target in osteoarthritis and rheumatoid arthritis', Osteoarthritis Cartilage, 2006; 14(9):839-848).

NF-κΒ transcription factors regulate several important physiological processes, including inflammation and immune responses, cell growth, apoptosis, and the expression of certain viral genes. Therefore, the NF-κB signaling pathway has also provided a focus for pharmacological intervention, primarily in situations of chronic inflammation or in cancer, where the pathway is often constitutively active and plays a key role in the disease. Now that many of the molecular details of the NF-κB pathway are known, it is clear that modulators of this pathway can act at several levels.

 Over 750 inhibitors of the NF-κΒ pathway have been identified, including a variety of natural and synthetic molecules. These compounds include antioxidants, peptides, small RNA/DNA, microbial and viral proteins, small molecules, and engineered dominant-negative or constitutively active polypeptides. Several of these molecules act as general inhibitors of NF-κΒ induction, whereas others inhibit specific pathways of induction. In addition, some compounds appear to target multiple steps in the NF-κB pathway. Pharmaceutical NF-κΒ inhibitors (for example, denosumab) are now entering the clinical arena. Moreover, the therapeutic and preventative effects of many natural products may, at least in part, be due to their ability to inhibit NF-κB.

 NF-κB is activated by multiple families of viruses, including human immunodeficiency virus 1 (HIV-1), human T-lymphotropic virus 1 (HTLV-1), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), and influenza virus. This activation may serve several functions: to promote viral replication, prevent virus-induced apoptosis, and mediate the immune response to the invading pathogen.

As viruses evolve under the highly selective pressures of the immune system, they acquire the capacity to target critical steps in the host cell life, hijacking vital cellular functions to promote viral pathogenesis. Many viruses have evolved mechanisms to target the NF-κΒ pathway to facilitate their replication, cell survival, and evasion of immune responses. In addition, some viruses use the NF-κΒ pathway either for its antiapoptotic properties to evade the host defense mechanisms or to trigger apoptosis as a mechanism of virus spread (Hiscott J, Kwon H and Genin P, 'Hostile takeovers: viral appropriation of the NF-κΒ pathway', J. Clin. Invest., 2001; 107(2): 143-151, doi:10.1172/JCI11918).

Increasing recognition of the benefits brought about by plant polyphenolics for human health has sparked a new appraisal of various plant-derived food and beverages, such as fruit juices, olive oil, chocolate, coffee, tea and even alcoholic beverages such as wine and cider.

However, excessive consumption of these polyphenolic foods often places a high calorific load on the human diet (for example, fruit juices such as pomegranate juice or cranberry juice), or in the case of caffeinated and alcoholic foods, excess intake results in negative health outcomes.

Plants have been widely used since antiquity as folk medicines. Some of these natural medicines contain the polyphenol antioxidant group, ellagitannins, as the principal "active" constituent.

This is where our first area of focus has been targeted. We have created up to 50 different foods, beverages and applications for this first area of focus. We are know working towards the next goal of another patent with further development in the areas of natural food science.