NDGA - Nordihydroguaiaretic Acid

NDGA is the bioactive component of the Mexican desert plant, Larrea Divaricata - an antioxidant, lipoxygenase inhibitor as well as an inhibitor of peptido-leukotriene biosynthesis

Chemical Name:
1,4-Bis (3,4-dihydroxyphenyl) -2,3-dimethylbutane;
NDGA CAS No. 500-38-9

Nordihydroguaiaretic Acid (NDGA) is a powerful antioxidant for use in skin care systems ranging from 0.001% to 0.01% w/w. Recent studies of NDGA have revealed biological properties as a free-radical scavenger and a protective agent against keratosis caused by exposure to UV light. NDGA is currently being tested to see if it can increase the lifespan of experimental animals.

Anti-inflammatory

Mitigates the inflammatory response in skin. NDGA inhibits the synthesis of inflammatory mediators such as prostaglandins and leukotrines by blocking the actions of the enzyme lipoxygenase. It prevents leukocyte infiltration into tissues and the release of reactive oxygen species. At higher concentrations it also inhibits cyclooxygenase. NDGA is able to block chemically induced skin irritation.

Blocks UV Effects

NDGA is a natural phenolic (resin) and prevents UV induced skin damage by inhibiting UVB-induced c-fos and AP-1 transactivation in the HaCaT keratinocyte cell line. NDGA blocks UV-induced gene activation of inflammatory cytokines in the skin.

Blocks Matrix Degradation

UVB induces the activity of matrix metalloproteases (MMP) expression. This induction causes the enzymatic breakdown of the support matrix in the skin, and results in fine lines and wrinkles (premature aging). NDGA blocks this effect by interfering with the UV effects on MMP activation.

Anticellulite

Reduces the accumulation of fat deposits in skin. NDGA prevents lipid accumulation in lipid storage cells, adipocytes.

Hair growth

NDGA reduces new hair growth and irritation from hair removal.

Anti-aging

Indirectly inhibits the production of enzymes that can break down the skin and reduces fine lines and wrinkles.

Anti-Acne

NDGA reduces the amount of sebum available to nourish bacteria or plug pores and helps clear visible blemishes.

NDGA is a bi-phenolic compound that is a component of the resinous exudates of many plants. In its structure, NDGA has two moles of antioxidant power in one molecule. Traditionally extracted from a plant (larrea divaricata), NDGA has been used for years as an oil-soluble antioxidant.

Physical and Chemical Properties

Empirical Formula: C18H22O4
Molecular Weight: 302.4

Specifications

Appearance - Crystalline solid
Solubility - Soluble in Ethanol and Methanol
Melting Point - 186-187°C
Bacteria and Fungi - <100 cfu/g
Assay - >99%
Storage - Keep sealed in a dry place
Solubility - Insoluble in water. 5gm diluted in 45ml IM NaOH forms haze free solution.
Application - Skin Care

Usage/Applications

Usage level in skin care products: 0.001% - 0. 1%.
In most cases, usage levels below 0.01% will deliver adequate antioxidant activity in a finished product.
For anti-inflammatory and UV protection, higher levels up to 0.1%.

Compatibility

NDGA antioxidant is stable and compatible with materials generally used in skin care products within a pH range of 4.5 - 7. It can be used in anionic, nonionic or cationic formulations.

Safety

Ocular irritation assay: Displayed minimal ocular irritation at concentrations up to 0.2%.
Dermal irritation assay: Classified as a non-irritant/ irritant at concentrations up to 0.2%.

Links to more information on NDGA

Involvement of arachidonic acid metabolism and EGF receptor in neurotensin-induced prostate cancer PC3 cell growth. Hassan S, Carraway RE. Regul Pept. 2005 Dec 1;

Overcoming trastuzumab resistance with nordihydroguaiaretic acid? Altundag K, Altundag O, et al., Breast Cancer Res Treat. 2005 Dec 1;:1

Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and c-erbB2/HER2/neu Receptors and Suppresses Growth in Breast Cancer Cells. Youngren JF, Gable K, Penaranda C, et al., Breast Cancer Res Treat. 2005 Nov;94(1):37-46.

Linoleic acid, but not oleic acid, upregulates production of interleukin-8 by human vascular smooth muscle cells via arachidonic acid metabolites under conditions of oxidative stress. Leik CE, Walsh SW. J Soc Gynecol Investig. 2005 Dec;12(8):593-8.

Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potassium currents in gastric myocytes. Yang M, Li XL, et al., Acta Pharmacol Sin. 2005 Oct;26(10):1233-42.

Protective effect of nordihydroguaiaretic acid (NDGA) against norgestrel induced genotoxic damage. Siddique YH, Beg T, Afzal M. Toxicol In Vitro. 2005 Jul 29;

Inhibition of influenza-virus-induced apoptosis in chorion cells of human fetal membranes by nordihydroguaiaretic Acid. Uchide N, Ohyama K, Bessho T, et al., Intervirology. 2005 Sep-Oct;48(5):336-40.

Sensitization of colon cancer cell lines to butyrate-mediated proliferation inhibition by combined application of indomethacin and nordihydroguaiaretic acid. Galfi P, Neogrady Z, Amberger A, et al. Cancer Detect Prev. 2005;29(3):276-85.

Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Arteaga S, Andrade-Cetto A, Cardenas R.J Ethnopharmacol. 2005 Apr 26;98(3):231-9.

Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells. Ito H, Ueda H, et al., J Cell Physiol. 2005 Mar;202(3):874-9.

Nordihydroguaiaretic acid inhibits IFN-gamma-induced STAT tyrosine phosphorylation in rat brain astrocytes. Jeon SB, Ji KA, et. al, Biochem Biophys Res Commun. 2005 Mar 11;328(2):595-600.

Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes. Gonzales M, Bowden GT. Mol Carcinog. 2002 Jun;34(2):102-11.

Preferential inhibition of platelet-derived growth factor-stimulated DNA synthesis and protein tyrosine phosphorylation by nordihydroguaiaretic acid. Domin J, Higgins T, Rozengurt E. J Biol Chem. 1994 Mar 18;269(11):8260-7.

Antimutagenic and antitumorigenic activities of nordihydroguaiaretic acid. Wang ZY, Agarwal R, Zhou ZC, et al., Mutat Res. 1991 Nov;261(3):153-62.

Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. Agarwal R, Wang ZY, Bik DP, Mukhtar H. Drug Metab Dispos. 1991 May-Jun;19(3):620-4.

Inhibition of benzoyl peroxide-mediated tumor promotion in 7, 12-dimethylbenz(a)anthracene-initiated skin of Sencar mice by antioxidants nordihydroguaiaretic acid and diallyl sulfide. Athar M, Raza H, Bickers DR, Mukhtar H. J Invest Dermatol. 1990 Feb;94(2):162-5.