Why Apocynin Regenerates Skin

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The fabled “fountain of youth” wasn’t just an intriguing physical location sought after by ancient explorers, but a concept that has captured the imaginations of ordinary mortals since the dawn of time. Some have pursued every avenue they could think of to help them live longer.

But like so many things in life, scientists found that a little healthy competition is all that’s needed — cell competition, that is. Scientists in Japan recently discovered a protein called COL17A1 that encourages cell competition by driving out weak cells and revitalizing stronger cells toward replication and, in the process, maintaining tissue fitness.

Aging and other stressors, such as excess ultraviolet radiation and damaging free radicals, take a toll on your skin, and so does steadily depleting COL17A1, as it replicates weaker cells, not stronger ones. The inevitable results: skin that is thinner, more prone to damage and takes longer to heal.

The research involved the use of mice tails because of their similarity to human skin.1 Emi Nishimura, a professor at the Tokyo Medical and Dental University’s stem cell biology department and leader of the featured study, noted that “Damaged or stressed stem cells can be selectively eliminated by intact stem cells every day in our skin.”

How COL17A1 ‘Rescues’ Aging Skin

When the researchers learned how important COL17A1 is in maintaining skin resilience, they set about investigating the possibility of stimulating it once it was depleted. They looked for compounds with the ability to “kick-start” the antiaging process and identified two chemical compounds: Both Y27632 and apocynin proved to produce positive results on skin cells, pointing to ways of “facilitating skin regeneration and reducing skin aging.” 

The two compounds “significantly promoted” repair and regeneration even to deep-tissue skin wounds, and it was done two ways, according to the study, published in the journal Nature.2 As the study authors observed:

“Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing.

Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention.”3

How Y27632 and Apocynin ‘Kick-Start’ Antiaging

When two professors from the University of Colorado reviewed the Tokyo study, they reported that fruit flies had been the only subjects ever closely scrutinized in regard to cell competition.

Ganna Bilousova and James DeGregori wrote that the research conducted by Nishimura and her colleagues could be considered “proof of principle” in regard to the ability of Y27632 and apocynin to fight aging. They also noted that the research “Provides evidence that healthy cells in mammals can also efficiently repopulate adult tissues, replacing unfit or damaged cells.”4

While conceding that more studies would be required to nail down the mechanisms responsible for cell competition in other tissues, Nishimura told news agency AFP5 they also hoped to identify compounds capable of performing the same antiaging functions in other organs.

She added, “We are working on other epithelial organs as well to find out (whether) similar competition may underlie long-term tissue maintenance as well as organ ageing.”6

She also noted the study team’s hope that the research would lead to the development of tablets, creams and other products that could halt the deterioration of and promote the repair of skin cells, and that they could “collaborate with pharmaceutical or cosmetic companies for the clinical use of the chemicals.”7 According to a Mediators of Inflammation study published in 2008:

“Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH-oxidase. It can decrease the production of superoxide from activated neutrophils and macrophages while the ability of phagocytosis remains unaffected.”8

In explanation, neutrophils are the most common type of white blood cells that help your body respond to infection and heal damaged tissue.9 Macrophages “act as antimicrobial warriors” that “play critical roles in immune regulation and wound healing.”10 Phagocytosis is described as a complex process for the ingestion and elimination of pathogens, and fundamental for tissue homeostasis.11

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Apocynin: What It Is and What It Does

Perhaps a simpler way of characterizing apocynin is to explore where it’s found. The 2008 inflammation study12 notes that it was first described in an investigation conducted in 1883 when the compound was isolated from the roots of Canadian hemp (Apocynum cannabinum) and used to treat dropsy and heart problems.

It was also found in the root of Picrorhiza kurroa, a plant with the faint odor of vanilla, native to India, Nepal, Tibet and Pakistan and common in Ayurvedic treatments. In India and Sri Lanka, extracts were used “for the treatment of ailments of liver, heart, joints, and lungs.”13

A 2014 study14 shows that the “small phenolic antioxidant” known as apocynin and extracted from the Jatropha multifida plant, also known as Guatemala rhubarb or coral plant, grown from Mexico to Central America to Brazil, was shown to have potential for treating neurodegenerative diseases.

Researchers also found apocynin to be one of five volatile vanilla flavor compounds in the vanilla bean, aka Vanilla planifolia.15 Another study suggested its cancer-fighting potential:

“The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model … (and) their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells.”16

Besides its advantageous effects on fighting inflammation and free radical scavenging, apocynin has a history of successful treatment of a long list of ailments, including:

  • Ischemia-reperfusion, characterized by damaged lung tissue due to a lack of oxygen and subsequent returned supply,17 with apocynin also showing potential in treating several other respiratory diseases
  • Possible neuroprotective abilities, particularly in brain injury following an eschemic stroke,18 as well as reduced cerebral and vascular injury in experimental stroke models19
  • Potential in the treatment of atherosclerosis due to reduced blood pressure,20 and preventing endothelial dysfunction21
  • Chronic inflammatory joint diseases such as osteoarthritis and rheumatoid arthritis22
  • Inhibiting tumor migration in breast cancer cells23

A 2014 study notes that “the perspectives for apocynin in chronic neurodegenerative disorders,” suggests a “potentially beneficial role” in amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease,24 Alzheimer’s25 and Parkinson’s disease.26 Although mouse models were the usual subjects in experimentation, the researchers are hopeful that apocynin will prove just as effective in human patients.

Other Beneficial Functions of Apocynin

Arguably the most important aspect of apocynin is its role in fighting inflammation, and the above study notes that it’s been demonstrated in a variety of cell and animal models. Apocynin also “inhibits the assembly of NADPH-oxidase that is responsible for reactive oxygen species (ROS) production.”27

The 2008 study explains NADPH-oxidase as the enzyme responsible for ROS production, so suppressing it is often the goal in disease prevention therapies. When antioxidants are in place or introduced, oxidative stress is diminished. Your body produces an “armory of antioxidants to defend itself,” which nonetheless are sometimes insufficient to effectively defend against ROS.

ROS damages your cells as well as your DNA, which is part of the reason your body begins showing signs of aging. To a large degree, how well your mitochondria work is determined by your diet, optimally a ketogenic diet (in which you replace carbs with moderate amounts of high-quality protein and high amounts of beneficial fat).

However, the featured study notes that it’s the excessive production of ROS that becomes damaging, and that’s how it’s been implicated in the progression of many diseases. It’s also why apocynin is noted as a potential treatment for many of them.

A Mediators of Inflammation review concluded that apocynin, besides its lack of known side effects, deserves further attention in the development of “safe and selective anti-inflammatory drugs which lack the often serious side effects of steroids.”28



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