Inhibiting the Destructive Effects of arNOX (ENOX3)

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The Aging-Related Cell Surface NADH Oxidase (arNOX) enzyme is one in a class of newly-identified ECTO-NOX (external NADH oxidase or ENOX (Ectos is Greek for outside) ) proteins that are located on external cell membranes.  arNOX is also known as ENOX3.

As the cells mitochondria age and produce less energy, arNOX becomes increasingly active.  arNOX is present in all cells tested, and in particular in the serum and saliva as well as the dermis and epidermis of the skin. 

ArNOX activity increases with age between 30 and 50–65 years and generates the destructive superoxide free radical.  arNOX transmits cell surface oxidative changes to surrounding cells and circulating lipoproteins. 

arNOX promotes tissue aging, especially in the vascular walls and the skin and the structural components of the skin’s extracellular matrix, such as collagen and elastin. arNOX is shed from the cell surface and is found in saliva, urine, perspiration, and interstitial fluids that surround the collagen and elastin matrix underlying dermis.

There is a strong correlation with the level of arNOX in the blood or saliva and a persons age.  The older one looks, apparently the more arNOX is in the blood and saliva.  arNOX is inactive in youth and can vary among individuals after age 30.  arNOX activity correlates with age and reaches a maximum at about age 65 in males and 55 in females.

Inhibiting arNOX by exogenous (dietary) natural substances is the only way to lessen and mitigate the destrucitve effects of arNOX.

Inhibiting arNOX activity

There are a number of natural substances that have been shown to inhibit arNOX activity and reduce oxidative damage caused by the superoxide free radical.  The following natural substances are able to inhibit arNOX:

Co-enzyme Q10 (CoQ10)

Co-enzyme Q, especially CoQ10 is capable of inhibiting arNOX.  1  The generation of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an anti-aging benefit of CoQ10 supplementation in human subjects.  arNOX activity was reduced between 25 and 30% by a 3 x 60 mg daily dose Coenzyme Q10 supplementation. Inhibition was the result of Coenzyme Q10 presence. 2

Tyrosol and Hydroxytyrosol

Tyrosol and Hydroxytyrosol are capable of inhibit arNOX activity.  3

Herbes de Provence

Based on the scientific research of James and Dorothy M. Morré, they demonstrated that natural compounds from French culinary seasonings – “Herbes de Provence” inhibit arNOX activity.  4

Herbes de Provence typically comprise:

  • basil (Ocimum basilicum)
  • fennel seed (Foeniculum vulgare)
  • marjoram (Origanum majorana)
  • oregano (Oreganum vulgare)
  • rosemary (Rosmarinus officinalis)
  • sage (Salvia officinalis)
  • summer savory (Satureja hortensis)
  • tarragon (or estragon, dragon’s-wort, Artemisia dracunculus)
  • thyme (Thymus vulgaris)

The ratio of these herbs that make up Herbes de Provence vary with personal or regional choice.

Of the herbs listed, the following are particularly active as arNOX inhibitors:

  • basil
  • tarragon (especially French tarragon)
  • rosemary
  • marjoram
  • sage
  • savory (especially summer savory)

Figure 1.  Summer Savory

Summer savory was the herb that had the highest arNOX activity inhibition at 89%.

Figure 2:  arNOX activity % inhibition.  (Source:  U.S. Patent 20120207862 A1)

According to U.S. Patent 20120207862 A1 entitled ORAL INHIBITORS OF AGE-RELATED NADH OXIDASE (arNOX), COMPOSITIONS AND NATURAL SOURCES, by the inventors, D. James Morré, Dorothy M. Morré, Thomas Shelton, components can be incorporated in the following proportions:

  • basil, 0-95%
  • thyme, 0-50%
  • oregano, 0-90%
  • tarragon, 0-95%
  • rosemary, 0-95%
  • lavender, 0-50%
  • sage, 0-95%
  • savory, 0-95%
  • marjoram, 0-95%

The U.S. Patent recommends the following dosages.  By formulating the herbal preparations as sustained-release preparations, 24 h of protection were attained with just two 400-mg capsules/day (one in the morning and one before bedtime) A preferred total daily dose is from about 200 mg to about 600 mg of a combination of herbs and/or natural products as described herein.