Nrf2 News & Reviews

International Formula Impact on Oxidative Stress
by GLEN THOMSON – NRF2.COM on MAY 4, 2014

Abstracts of the conference can be found at the Journal of the Federation of American Societies for Experimental Biology. 

Experimental Biology is an annual meeting attended by more than 14,000 scientists. The theme for 2014 was “Transforming the Future through Science.” The  Colorado State University study entitled Oxidative Stress is Decreased with Short-Term Protandim Use. The placebo-controlled double-blind study supplemented overweight/obese adults with ages from 45-69 for 30-days with “Nrf2 Activator” international formula currently sold in Japan. The results indicated a significant reduction in markers of oxidative stress in subjects receiving this Protandim formulation.

BY GLEN THOMSON – NRF2.COM ON APRIL 16, 2014
REVERSAL OF PERSISTENT FIBROSIS IN AGING BY TARGETING NOX4-NRF2 REDOX IMBALANCE

SCIENCEMAG.ORG

A brand new article in Sciencemag.org presents a study demonstrating how pathological fibrosis increases with age, but how NRF2 activation in mice was able to reverse the damage and repair lung capacity and fibrosis (scar tissue) resolution.

This is a promising study because the current treatments of pathological and cystic fibrosis are costly and very time consuming. Persistent fibrosis in lungs of aged mice was caused by the loss of cellular redox balance. The mice in the study with low NRF2 expression had a higher incidence of progressive lung disease. Tissues from human lung samples demonstrated this same Nox4-Nrf2 imbalance.

The abstract concludes with the following promising statement. “The studies suggest that restoration of Nox4-Nrf2 redox balance in myofibroblasts may be a therapeutic strategy in age-associated fibrotic disorders, potentially able to resolve persistent fibrosis or even reverse its progression.”

Inflammation: A Major Contributor to Disease and Aging. Can NRF2 Help Reduce It?
by GLEN THOMSON – NRF2.COM on OCTOBER 24, 2013

As the boomer generation ages it is probable that there will be more posts such as the one I saw this week from a friend on Facebook. Their plea was for suggestions and recommendations for a good solution to help alleviate the pain they were experiencing from inflammation.

Externally, inflammation can be recognized by redness, swelling and pain. Internally, it is a lot more difficult to to recognize and may well go undetected for long periods of time. The effects of inflammation can also range from minor to chronic. An example of a minor case of inflammation may include bacteria causing an infection such as from a splinter piercing the skin. The more serious chronic inflammation may be a common factor in many age-related diseases such as Diabetes, arthritis, heart disease, cancer or Alzheimer’s.

There are over 500 results on Pubmed.gov when searching NRF2 and inflammation. A couple of examples of the positive role that NRF2 had on inflammation.

The first study we will highlight is one called “Transcription Factor Nrf2 Regulates Inflammation” which was published in the Journal of Molecular and Cellular Biology. This inflammation. study dates back to 2003 in which two groups of mice with pleurisy were tested. The one group was treated with a Nrf2 activator, cyclooxygenase 2 inhibitor NS-398 the other group was not treated. The conclusion of the study shows that the mice with elevated NRF2 had less inflammation than the mice that were not treated.

“Administration of 15d-PGJ into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment. In contrast, these changes did not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2 regulates the inflammation process downstream of 15d-PGJ by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.”

The following study “Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis.” Published in the
European Journal of Immunology. shows the interaction between NRF2 and the inflammation causing protein called inflammasome.

Quoting from the study, “Here we have identified the oxidative stress-responsive transcription factor NF-E2-related 2 (Nrf2) as an essential positive regulator of inflammasome activation and IL-1-mediated vascular inflammation. We show that cholesterol crystals, which accumulate in atherosclerotic plaques, represent an endogenous danger signal that activates Nrf2 and the NLRP3 inflammasome.”

So, in response to my friend looking for solutions to their inflammation concerns, we suggest researching further in Pubmed and other reputable journals as well as getting the advice of a healthcare professional.

Spring Cleaning Damaged Proteins with NRF2: Good for Huntington’s Disease and Other Neurodegenerative Disorders?
by GLEN THOMSON – NRF2.COM on SEPTEMBER 5, 2013

A new study supported by grants from NINDS and the National Institute on Aging as well as funding provided by the Taube/Koret Center, the National Science Foundation , the Huntington’s Disease Society of America, the Milton Wexler Award, and the Hillblom Foundation shows that activating a gene known as NRF2 helps clear damaged proteins which slows down or could possibly prevent Huntington’s disease.

The study published in Nature Chemical Biology explains how important it is to quickly clear damaged proteins from neurons. Cell survival may be affected by the speed at which damaged proteins are removed. In Huntington’s disease and other neurodegenerative disorders, damaged proteins become misshaped and abnormal. They envelope neurons and damage or kill the nearby brain cells. Healthy bodies are able to control quality and quantity of protein levels, as well as is able to detect malformed proteins and flush them be fore they can do any damage through a process called proteostasis.


The study broke new ground in developing and using a technique called optical pulse-labeling to measure how quickly damaged proteins get removed. “Before this new technique, there was no way to look at individual neurons and their capacity to handle proteins. This method provides a real-time readout of how fast proteins are turned over in neurons and gives us a look at some of the mechanisms involved,” said Margaret Sutherland, Ph.D., program director at NINDS.

The research studied the impact of different forms of huntingtin, the protein in Huntington’s disease on neuron death and the symptoms of the disease. The experiments showed that the mutant form of huntingtin caused more rat cells to die than the normal healthy form of the protein.

To test this idea, the researchers activated Nrf2, a protein known to regulate protein processing. When Nrf2 was turned on, the mean lifetime of huntingtin was shortened, and the neuron lived longer. The researchers discovered that neuronal survival is directly correlated with the amount of time a neuron is exposed to the mutant huntingtin protein. Improving proteostasis in Huntington’s brains may improve neuronal survival and slow down or even prevent the the progression of the disease.

“Nrf2 seems like a potentially exciting therapeutic target. It is profoundly neuroprotective in our Huntington’s model and it accelerates the clearance of mutant huntingtin,” said Dr. Steven Finkbeiner, senior author of the paper.

“These findings provide evidence that our brains have powerful coping mechanisms to deal with disease-causing proteins. The fact that some of these diseases don’t cause symptoms we can detect until the fourth or fifth decade of life, even when the gene has been present since birth, suggests that those mechanisms are pretty good,” said Dr. Finkbeiner.

NRF2 Benefits for Weight-loss, Obesity and Metabolic Syndrome
by GLEN THOMSON – NRF2.COM on JUNE 18, 2013

The Center for Disease Control (CDC) states that obesity is a significant public health problem. The “Healthy People” initiative shows that not one state in the United States meets the Healthy People goal of 15% body mass index (BMI).

Thirty states missed the goal by a percentage by 10% or more. Data was collected from the Behavioral Risk Factor Surveillance System (BRFSS).

Obesity and its associated metabolic disorders have been classified as a growing health epidemic and is causing a major strain on health systems. Overall, the health picture shows that overall 25.6% of respondents were considered obese, 26.4% of men were obese and 24.8% of women. The most at risk age group for both men and women was those aged 50–59 years.

Obesity vs Being Overweight

There is a difference between being obese and being overweight. Obesity is characterized by having too much body fat. Being overweight may be described as weighing too much. Weight may result from muscle, bone, fat, and/or body water.

Obesity occurs over a period of time as a person consumes more calories than they use. Factors impacting weight include genetics, diet, and lack of physical activity.
Obesity has been associated with diseases such as diabetes, certain cancers, heart disease, stroke and arthritis.

Overcoming Obesity

Medical experts promote that 10% to 15% weight loss will make a big difference in lowering heath risks associated with obesity. Weight-loss can be achieved through healthy dietary changes as well as increased physical activity. Prescription medications or weight-loss surgery are also options to discuss with a medical professional. In considering a healthy diet, this article will investigate the impact that NRF2 synergy can have on obesity.

NRF2 Obesity Studies:

Obviously NRF2 activation alone would be insufficient to tackle obesity. However, there are some very interesting studies that show a healthy NRF2 pathway in the body does help manage obesity. The purpose of sharing some extracts from various health related NRF2 obesity studies is to encourage you to do further in-depth research for yourself, to whet the appetite for learning more about the topic. We share this information for educational purposes only. Consult with a medical professional for professional advice regarding any questions you have regarding obesity and weight-loss.


Adipose Deficiency of Nrf2 in ob/ob Mice Results in Severe Metabolic Syndrome


http://www.ncbi.nlm.nih.gov/pubmed/23238296

Two quotes from this study are fascinating to those interested in NRF2 Science.

1. “Our findings support a novel role for Nrf2 in regulating adipose development and function, by which Nrf2 controls the capacity of WAT expansion and insulin sensitivity and maintains glucose and lipid homeostasis.”

2. “In light of the new function of Nrf2 in adipogenesis and its canonical role in adaptive antioxidant response, our results suggest a novel mechanistic linkage between metabolic syndrome and oxidative stress, opening the possibility that manipulation of Nrf2 may prevent or treat obesity and associated metabolic syndrome.”

The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism.


The Journal Of Nutritional Biochemistry [J Nutr Biochem] 2012 Oct; Vol. 23 (10), pp. 1201-6. Date of Electronic Publication: 2012 Jul 21.

This study also has some interesting findings related to NRF2, metabolism, fatty diets, obesity and diseases such as diabetes.

“Recently, the Nrf2 pathway was identified as having regulatory functions in mitochondrial biogenesis, adipocyte differentiation and liver energy metabolism. Activation of Nrf2 increases energy metabolism and conversely suppresses lipid synthesis. Lard-based, but not soybean oil-based, high-fat diets reduce mRNA expression of Nrf2 and its downstream targets, suggesting a macronutrient influence on the activation of the Nrf2 pathway and susceptibility to oxidative stress. This review examines data revealing the Nrf2 pathway’s regulatory role in energy metabolism at the molecular, cellular and whole animal levels. Understanding the relationship of Nrf2 and energy metabolism in cells, tissues and physiologic systems will provide novel insights for nutritional interventions for obesity and its comorbidities such as diabetes.”

Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide.


European Journal Of Pharmacology [Eur J Pharmacol] 2009 Oct 12; Vol. 620 (1-3), pp. 138-44. Date of Electronic Publication: 2009 Aug 19.

“CDDO-Imidazolide or CDDO-Im is an extremely potent activator of Nrf2 signaling. In cells undergoing adipogenesis, CDDO-Im prevents lipid accumulation in an Nrf2-dependent manner. However, in vivo evidence for effects of CDDO-Im on obesity is lacking. The goals of these studies were to determine if CDDO-Im can prevent high-fat diet-induced obesogenesis in the mouse, and to elucidate the molecular target of drug action. Wild-type and Nrf2-disrupted C57BL/6J female mice were dosed 3 times per week with 30 micromol/kg CDDO-Im or vehicle by oral gavage, during 95 days of access to a control diet or a high-fat diet. Body weights, organ weights, hepatic fat accumulation and gene expression were measured. Treatment with CDDO-Im effectively prevented high-fat diet-induced increases in body weight, adipose mass, and hepatic lipid accumulation in wild-type mice but not in Nrf2-disrupted mice. Wild-type mice on a high-fat diet and treated with CDDO-Im exhibited higher oxygen consumption and energy expenditure than vehicle-treated mice, while food intake was lower in CDDO-Im-treated than vehicle-treated mice. Levels of gene transcripts for fatty acid synthesis enzymes were downregulated after CDDO-Im treatment in the liver of wild-type mice. This inhibitory effect of CDDO-Im on lipogenic gene expression was significantly reduced in Nrf2-disrupted mice. The results indicate that CDDO-Im is an exceedingly potent agent for preventing obesity, and identify the Nrf2 pathway as a novel target for management of obesogenesis.

Those familiar with NRF2 activation are aware that curcumin is a potent NRF2 activator. This next study investigates whether there are any health benefits from curcumin on weight-loss.

“New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases.”
European Journal of Nutrition, Apr 2011

“The interactions of curcumin with several signal transduction pathways reverse insulin resistance, hyperglycemia, hyperlipidemia, and other inflammatory symptoms associated with obesity and metabolic diseases.”

“The modulation of several cellular transduction pathways by curcumin has recently been extended to elucidate the molecular basis for obesity and obesity-related metabolic diseases. These findings might enable novel phytochemical treatment strategies as well as curcumin translation to the clinical practice for the treatment and prevention of obesity-related chronic diseases.”

Emerging role of Nrf2 in adipocytes and adipose biology.


Advances In Nutrition (Bethesda, Md.) [Adv Nutr] 2013 Jan 01; Vol. 4 (1), pp. 62-6

“Maintenance of a balanced redox state within the cell is of critical importance to a wide variety of biological systems. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a critical regulator of key aspects of the antioxidant defense pathway and has long been a subject of interest regarding conditions of chronic stress such as inflammation and cancer. Recent data have emerged demonstrating that oxidative stress and Nrf2 also play critical roles in the biology of adipose tissue. This review examines data identifying the roles of Nrf2 and oxidative stress in the biological process of adipose cell differentiation as well as the implications of Nrf2 modulation on obesity. Working to understand the complex interplay among Nrf2, oxidative stress, and adipose biology could lead to a variety of possible treatments for obesity and other related disorders.”

New player on an old field; the keap1/Nrf2 pathway as a target for treatment of type 2 diabetes and metabolic syndrome.
Current Diabetes Reviews [Curr Diabetes Rev] 2013 Mar 1; Vol. 9 (2), pp. 137-45

“Nuclear erythroid factor 2 like 2 (Nrf2) has been described as a transcription factor that serves as a master regulator of the adaptive response to exogenous and endogenous oxidative and electrophilic stresses. Evidence of Nrf2 crosstalk with other molecular pathways is increasing; recent publications have proposed a role of Nrf2 in the development of obesity and in the highly regulated process of adipocyte differentiation through its interaction with other transcription factors and receptors implicated in metabolic regulation. In the present review, we discuss the available data on the possible role of Nrf2 in obesity and metabolic syndrome and the feasibility of using Nrf2 as a therapeutic target in the clinical setting.”

*Information provided on this site is for educational purposes only. Do your own research, and consult with a medical professional about your findings. “Nrf2 activator” is a dietary supplement, not a drug. We do not promote or intend to imply or represent that it can prevent, cure, treat or mitigate any disease or class of disease. “Nrf2 activator” is not intended to be an alternative or replacement for any drug or biological product.