Home PPARs reemerging as a skin wellness target in cosmetics

PPARs reemerging as a skin wellness target in cosmetics

PPARs reemerging as a skin wellness target in cosmetics

Written by Marc Cornell, Mar-Key Consulting LLC

Cosmetics are continuing their marvelous evolution with new scientific findings and breakthrough innovations. Sometimes we need to look back to find the genesis of a current marketing or positioning trend. Take a step back with me to the late 20th century, where a young researcher (MC) was being educated in the biology of wound healing. During this time, I became aware of Peroxisome proliferator-activated receptors (PPARs). PPAR-alpha expression plays a role in the inflammatory stage of wound healing. Later I learned wound healing shares many biologic pathways with anti-age biology.  Peroxisome proliferator-activated receptors is a mouthful, right? Let’s dial it back bit and keep the PPAR focus on our body’s largest organ, the skin.

PPAR’s are ligand inducible transcription factors belonging to the nuclear hormone receptor superfamily. The key isoforms of PPARs are notated as (alpha), (beta/delta) and (gamma). These forms can up regulate or down regulate many cellular and metabolic processes (cellular differentiation, proliferation, lipid homeostasis and energy metabolism). These functions are critical to our body and its skin’s immune system, epidermal barrier function and development of pro-inflammatory signals. Peroxisome proliferator-activated receptors (PPARs) are also involved in regulating glucose, lipid homeostasis and modulate mitochondrial function. (1)  It is obvious that regulation of PPAR signaling to various biological systems is an opportunity for medicine and cosmetic science

In some publications, regulation of PPAR signaling have been linked to disease pathogenesis. These ailments have complex causes involving genetic, environmental, and nutritional factors, PPARS are just a part of the pathway. (2) In cosmetic science we are careful to draw the line between drug and cosmetic claims. With that said, there are numerous scientific studies elucidating shared connections between drug and cosmetic active biologic modes of action.

Now we take a partial deep dive on the FAQ’s for PPARS.  From there we will highlight how targeting PPAR’s has been around for some time in cosmetics. More recently these chemistries are trending in a big way as clinical branded cosmetics remerge as part of the wellness positioning.

How can cosmetic science leverage PPARS to facilitate skin wellness? We start our PPAR discussion by looking at the skin barrier function. This area of skin biology is also part of a recent trend towards positioning and the minimization of environmental stressors on the exposome. The exposome is defined as the measure of all the exposures of an individual in a lifetime and how those exposures relate to health.  PPAR activation has been shown to have an important role in skin barrier function by regulating differentiation and lipid synthesis in keratinocytes. (3) This fact fits nicely into homeostasis wellness positioning.

PPAR activation takes place through heterodimerization.  Simply put, you need 2 ligands to come together on the DNA to initiate gene regulation.  PPAR activators are already being used in areas of cosmetic science application.  Botanical extracts have been shown to activate PPAR in the stimulation of collagen in skin (4). There is also evidence that PPARs may be used as an alternative to retinoids in skin care. (5) PPARs have an important effect in keratinocyte homeostasis, suggesting a role in diseases such as psoriasis. (6)   PPAR acts directly to negatively regulate gene expression of proinflammatory genes in a ligand-dependent manner by antagonizing the activities of transcription factors such as members of the NF-kB and AP-1 families. (7).  One very popular cosmetic application is the use of omega 3 fatty acids.  These are popular natural ligands for PPARα receptors and are key to preventing/reducing inflammation.

One critical factor in attempting to utilize pathways linked to PPARs is in the understanding of the up or down regulation of these biochemicals. Typical of any biologic system there is potential for biofeedback, so understanding the pathways and assay methodologies are important. Good news is gene expression and cell culture models now allow the high throughput analysis of materials which may take part in PPAR regulation. This fact and the numerous peer review publications give the cosmetic chemist a boost in the study of PPARs.

In closing I provide just a few key words for continued education on PPARs.

Links between PPAR and:

a) Endocannabinoid receptor system
b) Hyaluronic acid
c) Wound healing
d) Retinoid receptor system
e) UV modulated inflammation
f) Inflamaging
g) Mitochondrial function
h) and MORE!

  1. Ting-Wei Lee, Kuan-Jen Bai, Ting-I Lee, Tze-Fan Chao, Yu-Hsun Kao & Yi-Jen Chen : PPARs modulate cardiac metabolism and mitochondrial function in diabetes Journal of Biomedical Science volume 24, Article number: 5 (2017)
  2. Kersten S, Desvergne B, Wahli W. : Roles of PPARs in health and disease. Nature. 2000; 405: 421–4. NATURE
  3. Su-Hyoun Chon , Ruth Tannahill, Xiang Yao, Michael D Southall, Apostolos Pappas. Keratinocyte differentiation and upregulation of ceramide synthesis induced by an oat lipid extract via the activation of PPAR pathways , Exp Dermatol. 2015 Apr;24 (4):290-5
  4. George P. Majewski1 | Smrita Singh2 | Krzysztof Bojanowski :Olive leaf-derived PPAR agonist complex induces collagen IV synthesis in human skin models, Int J Cosmet Sci. 2021;43:662–676
  5. John Simon Craw, George Majewski: Coding Skin for Care: PPAR Ligands as Retinoid Alternatives and Adjuvants—Cosmetic and Toiletries, Jan 6th, 2022
  6. Emerson de Andrade Lima1 et al : Peroxisome proliferator-activated receptor agonists (PPARs): a promising prospect in the treatment of psoriasis and psoriatic arthritis* An Bras Dermatol. 2013;88(6):1029-35.
  7. Yuval Ramot et al, The role of PPAR-mediated signaling in skin biology and pathology: new targets and opportunities for clinical dermatology : Experimental Dermatology, 2015, 24, 245–251

 

Written by Marc Cornell, Mar-Key Consulting LLC

Marc Cornell, BS. is a consultant at Mar-key Consulting LLC where he services the consumer product industry with innovative formulation concepts.  During his thirty-year career he has worked in an R&D role for large (Merck, L’Oreal, Bristol Meyers Squibb, Union Carbide) and medium sized companies (Neostrata, ChemAid Labs, KV Pharmaceutical). For the last ­20 years he has worked primarily on the research and formulation development of “Cosmeceuticals” for various brands (Skinceuticals, Neostrata, Dr. Perricone, Biomedic, Strivectin, and La Roche Posay). In this role he collaborated with researchers in skin biology and clinical testing to design, formulate and test novel cosmetic active delivery vehicles. Marc’s work has been patented and published in peer review journals and trade publications.

 

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