Cortisol, Blood Flow vs. Elasticity, and Neurocosmetics at IFSCC19


Cosmetic product developers have always taken the science seriously, delving deeply into biology and crossing into the grey areas of pharma and medical chemistries. But just when you think it's reached an apex, another IFSCC Conference comes around and proves you wrong. The hard-core science presented this year is the perfect example.

The opening ceremony of the IFSCC 2019 Conference, featuring a keynote on crystal engineering, alluded well to what would come, and the first day of sessions did not disappoint. From the opening talk on botulinum toxin, and subsequent discussions of TRPV receptor reactivity, biometric measurements of user response, and stress and cortisol release, to the effects of skin vasculature and blood flow on skin elasticity, IFSCC presenters tread into the grey areas of cosmeceuticals/quasi-drugs.

Botulinum Toxin

Cesare Montecucco, Professor Emeritus of General Pathology at the University of Padova, provided the opening keynote lecture on botulinum toxin. Montecucco works in the laboratory of neuroparalysis and neuroregeneration, where he aims to discover factors and signals involved in the regeneration of the neuromuscular junction. 

According to his paper abstract, botulism is a paralysis of peripheral cholinergic nerve terminals caused by botulinum neurotoxins (BoNTs). These are produced by anaerobic bacteria of the genus Clostridium, and are the most poisonous substances known to humans—in fact, they are included in the list A of potential bioterrorist weapons.

Yet, thanks to scientific and clinical research, they are therapeutics used in millions of doses to treat humans. Traditionally, seven types were known but genomics have recently characterized more than 40 types. Advances also have been made on the mechanism of nerve terminal entry, which involves the translocation of a metalloprotease domain such that it cleaves any of the three SNARE proteins. These proteins mediate the Ca2+-controlled release of neurotransmitters at the synapse.

Montecucco shared new findings on mechanisms of the metalloprotease activity that enabled the discovery a group of molecules to inhibit this redox system, preventing reduction and paralysis in vivo. He also discussed the pharmacological implications and cosmetic uses of botulinum neurotoxin type A.

Capsaicinoid for Sensitive Skin

Improving the design of natural compounds for "neurocosmeceuticals" was presented by Maria J. Lopez of AntalGenics. She explained the role of TRPV receptors in skin sensation and described work to target TRPV1 to calm the skin as well as inhibit itch.

She introduced an innovative capsaicinoid molecule, hydroxymethoxyiodobenzyl glycolamide pelargonate (AG1549), which improves the biological properties of the natural ingredient capsaicin. This compound antagonized TRPV1 neuronal receptor activity in a dose-dependent manner, in turn suppressing neuropeptide release, inflammation and pruritogenic signalling; while being devoid of the capsaicin burning sensation. 

In addition, AG1549 reduced chemically-induced oxidative stress in primary epidermal keratinocytes. This antioxidant effect was higher than the reference ascorbic acid, highlighting the ingredient's potential to prevent lipid oxidation and damage.

"The take home message is: Our ingredient has antioxidant, improved barrier function and calming effects," said Lopez. During the Q&A session, she also noted it could potentially relieve symptoms of psoriasis.

Stress, Cortisol Release and Wellness

Giulia Tanzi, of Davines S.p.A., shared research conducted in conjunction the University of Parma on stress, the stress response and how a cosmetic routine can reduce the stress response. "Stress is all around us," she said. "A little stress is okay but too much is not. It can lead to depression and anxiety and cause diseases. And while traditional pharmaceuticals can reduce stress, they can cause side effects and addiction. So it’s fundamental to find other ways to address stress."

The project sought to assess the potential anti-stress effects of a cosmetic routine by measuring the effects, in 40 subjects ages 25-50, of consistent self-application for 28 days of a cream enriched with four essential oils (or not, as the placebo). The test product was in a balm format, produced a cool feel upon application, and included essential oils. The placebo was a non-optimized, basic formula. For the test product application, panelists were instructed to use a mindful massage technique, with specific movements of application. 

Effects were assessed through noninvasive measurements of the autonomic nervous system, i.e., variability of heart rate, and of the hypothalamic-pituitary-adrenal axis, i.e., salivary cortisol levels. Test subjects also provided feedback, and nonverbal ethnological behaviors were recorded. At the end of the study, subjects also were assigned tasks under social pressure (i.e., answering questions in front of an unknown observer) to induce stress and, again, responses were recorded. Measurements were taken at days 0 and 29—one day after the final application.

"We got surprisingly good results," said Tanzi. "Both creams lowered the heart rate of users, although the test cream performed better than placebo. No big differences in effects were seen between the creams after 28 days, but after the added psychosocial stress, the test cream showed much lower cortisol release than placebo. Nonverbal behavior also showed reduced anxiety in test cream, compared with placebo."

Tanzi noted this is a market opportunity to further investigate the effects of cosmetic routine on stress. During the Q&A session, one attendee asked, "What kind of claim can you make with these results?" She responded, "Helps to reduce tension with anti-stress effects." Furthermore, she clarified the percentage of essential oil used was 0.5%. 

Melatonin-like Beauty Effects

"Is beauty sleep real? Can sleep beautify skin?" asked Alexandra Lan, of the Shanghai Pechoin Cosmetics Group. According to Lan, in skin, the melatonin receptor MT1 has been implicated in a number of different functions, from wound healing, reduction of erythema and hair growth regulation, to the inhibition of aging/senescence. In fact, melatonin levels and MT1 expression decrease with age, and MT1 appears strongly affected by oxidative stress and UV irradiation.

The main goal of this study was to identify new active ingredients that, by activating the MT1 receptor, could safely reinforce natural skin defense responses to attenuate aging-associated signs of stress. Screening various plants by cell culture on the criteria of MT1 reactivity led to the discovery of Helianthus annuus.

Various tests indicated the Helianthus annuus cell culture extract stimulated the melatonin/MT1 signalling pathway, with subsequent downstream benefits including anti-oxidant/free radical-scavenging power and matrix repair, and reducing the signs of ROS-generated stress via melatonin-like effects.

So the answer to her initial question was: yes.

Blood Flow and Skin Elasticity

Finally, Takagaki Kazuki, of Shiseido, explored the vasculature of skin in relation to elasticity. As stated in the paper abstract, "There seems to be ever-increasing interest for 'holistic beauty' in the cosmetic field, which refers to the idea that skin is not a separate organ but is physically and functionally connected to the body through its vascular, immune and endocrine systems. Oriental medicine has the view that skin is a mirror of the rest of the body. This perhaps shows that the connection between the skin and body has long been emphasized in Asia.

"Following this, in Western medicine, as William Osler stated, 'A man is as old as his arteries.' [Furthermore], vascular function is particularly related to the aging process, which includes the skin. However, the relevance of blood vessels to the process of skin aging, including their physical properties, still remains to be elucidated."

This inspired the work by Kazuki and colleagues. "Capillaries and scaffolds change with age," he explained, and demonstrated using a non-invasive technique to visualize capillaries. "Our hypothesis [was that] capillaries change skin elasticity." The team made a 3-dimensional macroscopic visualization of capillaries in human skin that revealed capillaries are densely and uniformly networked in the upper dermis but were reduced with photo-aging.

In this study, they found a strong relevance between capillaries and skin elasticity through in vitro and in vivo experiments. Greater blood flow meant higher elasticity, and changes in blood vessels could change elasticity. They also explored the potential of blood vessels to rejuvenate skin and observed type I collagen exiting the vessels, contributing to collagen production in the skin.

This work inspired several questions from attendees regarding how blood vessels were visualized and other skin entities to explore—no doubt fueling future research.

Follow us as we continue our reports from the IFSCC 2019 Conference.

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