Nrf2 is a transcription factor that regulates the antioxidant response of the body.1 It is the primary cellular defense against the cytotoxic effects of oxidative stress.2 This key protein is found inside a cell and is inactive until it is released by an Nrf2 activator. Once activated, Nrf2 migrates into the nucleus and binds to DNA at the location of the master antioxidant regulator, the antioxidant response element (ARE).3 Studies suggest Nrf2 plays an important role in supporting the activation of cellular antioxidant systems, as well as maintaining normal inflammatory balance.4,5 A number of fruit and vegetable compounds have been shown to activate Nrf2 and ARE, and increase antioxidant potential.6-9 It is believed that these compounds have a protective effect on the body, help maintain normal inflammatory balance, and induce cellular longevity.10
Broccoli Seed Extract†
Broccoli seed extract has the highest levels of glucoraphanin (a potent Nrf2 stimulator) of any broccoli product available.11 In fact, 230 mg of broccoli seed extract is equivalent to consuming 1 1⁄4 cups of fresh broccoli. Glucoraphanin is a phytochemical compound that acts as the precursor to sulforaphane, one of the leading compounds in broccoli that is responsible for many of its positive benefits.12,13 These compounds and their mechanisms have been studied extensively and supported by more than 500 scientific publications. Glucoraphanin and sulforaphane act as direct activators of Nrf2 and potent antioxidants shown to support detoxification and maintain normal inflammatory balance.14-18 Studies show they work by improving hormone balance and increasing functional enzymes that support excretion of toxins from the body.19 Broccoli seed extract has been shown to remain active within the body for up to three days following consumption.20
Andrographis (Andrographis paniculata) is an herbaceous plant native in India and Sri Lanka. It has widely been used in Southeastern Asian medicine for its broad range of health- promoting properties. In recent years, andrographis has emerged as a potent activator of Nrf2.1 Recent studies have shown that when compared to other phenolic compounds, 60 mg of andrographis induced the highest activation of Nrf2.2 This activation helps reduce oxidative stress, quench free radicals, maintain endothelial health and support mitochondrial function.2-4
Resveratrol, the most well-researched stilbene, is found in many plants and red wines. Studies of resveratrol have found it to enhance the potential of antioxidant and detoxification activity through Nrf2 activation.30 Other studies have linked resveratrol to enhancing blood sugar balance, maintaining normal inflammatory balance and reducing oxidative stress.31, 32
Turmeric (Complete Turmeric Matrix)†
Whole-root turmeric and its active components have been used in traditional Ayurvedic medicine for centuries. In herbal medicine of old, practitioners used teas, tinctures and extracts of all types. In the 21st century, as research grew on the benefits of turmeric, the focus shifted to identifying and isolating one individual compound, curcumin, rather than delivering the comprehensive benefits of a matrix of turmeric bioactives. As a result, concentrating curcumin led to poor absorption and pharmaceutical methods were applied to bypass the gut and increase its bioavailability. The glaring disadvantage of applying this pharmaceutical model to botanicals is that it misses the benefits of other bioactives present within the turmeric matrix and their positive effects on the microbiome. New research on turmeric shows the additional bioactives in turmeric have additional benefits and enhance bioavailability. The Complete Turmeric Matrix includes compounds from the entire turmeric root, all working together as nature intended to deliver better results. The Complete Turmeric Matrix formulation contains standardized amounts of 45%–55% curcuminoids, 2%-6% turmerin protein and 3%-8% volatile oil, plus other components that make up the whole turmeric root. This matrix of bioactive compounds supports a healthy GI tract, enhances detoxification, creates a healthy microbiome, and helps maintain normal inflammatory balance. Specifically, turmeric and its phytonutrients, like curcumin, have been shown to play a crucial role in maintaining normal inflammatory balance in a variety of bodily systems due to its ability to modulate Nrf2.25 Studies have shown curcumin maintains normal inflammatory balance in endothelial cells and cardiac cells.26-28 Curcumin has also been found to provide antioxidant protection to the cardiovascular system by reducing oxidative stress and supporting a normal immune response.29
† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
- Wong SY, Tan MG, Wong PT, et al. Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK. Journal of neuroinflammation 2016;13(1):251.
- Wu KC, McDonald PR, Liu J, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway. Planta medica 2014;80(1):97.
- Rajagopal S, Kumar RA, Deevi DS, et al. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. Journal of Experimental therapeutics and Oncology 2003;3(3):147-58.
- Mishra SK, Sangwan NS, Sangwan RS. Phcog Rev.: Plant Review Andrographis paniculata (Kalmegh): A Review. Pharmacognosy Reviews 2007;1(2):283-98.
- Li W, Khor TO, Xu C, Shen G, Jeong W-S, Yu S and Kong A-N. Activation of Nrf2-antioxidant signaling attenuates NFκB- inflammatory response and elicits apoptosis. Biochemical pharmacology. 2008;76:1485-1489.
- Surh Y-J, Kundu JK and Na H-K. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta medica. 2008;74:1526-1539.
- Surh Y-J and Na H-K. NF-κB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals. Genes & nutrition. 2008;2:313-317.
- Lee JH, Khor TO, Shu L, Su Z-Y, Fuentes F and Kong A-NT. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacology & therapeutics. 2013;137:153-171.
- Gopalakrishnan A and Kong A-NT. Anticarcinogenesis by dietary phytochemicals: cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-κB and AP-1 in abnormal cancer cells. Food and Chemical Toxicology. 2008;46:1257-1270.
- Su Z-Y, Shu L, Khor TO, Lee JH, Fuentes F and Kong A-NT. A perspective on dietary phytochemicals and cancer chemoprevention: oxidative stress, nrf2, and epigenomics Natural Products in Cancer Prevention and Therapy: Springer; 2012: 133-162.
- McWalter GK, Higgins LG, McLellan LI, Henderson CJ, Song L, Thornalley PJ, Itoh K, Yamamoto M and Hayes JD. Transcription factor Nrf2 is essential for induction of NAD (P) H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. The Journal of nutrition. 2004;134:3499S-3506S.
- Zhang Y, Kensler TW, Cho C-G, Posner GH and Talalay P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proceedings of the National Academy of Sciences. 1994;91:3147-3150.
- Clarke JD, Dashwood RH and Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer letters. 2008;269:291-304.
- Singh AV, Xiao D, Lew KL, Dhir R and Singh SV. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. 2004;25:83-90.
- Li Y, Zhang T, Korkaya H, Liu S, Lee H-F, Newman B, Yu Y, Clouthier SG, Schwartz SJ and Wicha MS. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clinical Cancer Research. 2010;16:2580-2590.
- HeissE,HerhausC,KlimoK,BartschHandGerhäuserC. Nuclear factor κB is a molecular target for sulforaphane- mediated anti-inflammatory mechanisms. Journal of Biological Chemistry. 2001;276:32008-32015.
- ThimmulappaRK,MaiKH,SrisumaS,KenslerTW,Yamamoto M and Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer research. 2002;62:5196-5203.
- Morimitsu Y, Nakagawa Y, Hayashi K, Fujii H, Kumagai T, Nakamura Y, Osawa T, Horio F, Itoh K and Iida K. A sulforaphane analogue that potently activates the Nrf2- dependent detoxification pathway. Journal of Biological Chemistry. 2002;277:3456-3463.
- Juge N, Mithen R and Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cellular and Molecular Life Sciences. 2007;64:1105- 1127.
- HanlonN,ColdhamN,GielbertA,KuhnertN,SauerMJ, King LJ and Ioannides C. Absolute bioavailability and dose- dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat. British Journal of Nutrition. 2008;99:559-564.
- Nishinaka T, Ichijo Y, Ito M, Kimura M, Katsuyama M,
Iwata K, Miura T, Terada T and Yabe-Nishimura C. Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element. Toxicology letters. 2007;170:238-247.
- Tapia E, Soto V, Ortiz-Vega KM, Zarco-Márquez G, Molina- Jijón E, Cristóbal-García M, Santamaría J, García-Niño WR, Correa F and Zazueta C. Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats. Oxidative medicine and cellular longevity. 2012;2012.
- Aggarwal BB and Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The international journal of biochemistry & cell biology. 2009;41:40-59.
- Zhang F, Altorki NK, Mestre JR, Subbaramaiah K and Dannenberg AJ. Curcumin inhibits cyclooxygenase-2 transcription in bile acid-and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 1999;20:445-451.
- BalogunE,HoqueM,PengfeiG,KilleenE,GreenCJ,Foresti R, Jawed A and Motterlini R. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochemical Journal. 2003;371:887-895.
an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radical Biology and Medicine. 2000;28:1303-1312.
- FiorilloC,BecattiM,PensalfiniA,CecchiC,LanzilaoL, Donzelli G, Nassi N, Giannini L, Borchi E and Nassi P. Curcumin protects cardiac cells against ischemia-reperfusion injury: effects on oxidative stress, NF-κB, and JNK pathways. Free Radical Biology and Medicine. 2008;45:839-846.
- YehC-H,ChenT-P,WuY-C,LinY-MandLinPJ.Inhibition of NFκB Activation with Curcumin Attenuates Plasma Inflammatory Cytokines Surge and Cardiomyocytic Apoptosis Following Cardiac Ischemia/Reperfusion 1. Journal of Surgical Research. 2005;125:109-116.
and atherosclerotic heart disease. New England Journal of Medicine. 1997;337:408-416.
- Kode A, Rajendrasozhan S, Caito S, Yang S-R, Megson IL and Rahman I. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2008;294:L478-L488.
- SuH-C,HungL-MandChenJ-K.Resveratrol,aredwine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. American Journal of Physiology-Endocrinology and Metabolism. 2006;290:E1339-E1346.
- MartỉAR,VillegasI,LaCasaCanddelaLastraCA. Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochemical pharmacology. 2004;67:1399-1410.
Always be sure to speak with your healthcare provider before starting any new nutritional supplement when pregnant or nursing. For children, we recommend speaking with your child's pediatrician regarding proper dosing. Store away from children.