Effect of regioisomers of hydroxystearic acids as peroxisomal proliferator-activated receptor agonists to boost the anti-ageing potential of retinoids

Introduction: We report on the in vitro and ex vivo effects of chiral (R)-10-hydroxystearic acid (10-HSA) compared with Other mono-hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol.

Methods: Following treatment with hydroxystearic acids peroxisomal proliferator-activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, Collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast Collagen proteome was studied by mass-spectrometry-based proteomics and Collagen type III was assessed by immunohistochemistry on human ex vivo skin.

Results: 10-HSA was the most effective PPARα Agonist (15.7× induction; p < 0.001), followed by 9-HSA (10.1× induction) and then 12-HSA (4.9× induction) with 17-HSA (1.7× induction) being similar to the effects of stearic acid (1.8× induction). Collagen type I levels were increased in primary human fibroblasts by 2.12× and 1.56× for 10-HSA and 9-HSA, respectively, in vitro with the10-HSA being significant (p < 0.05), whereas 12-HSA and SA had no statistical effect over the untreated control. 10-HSA and 12-HSA modified the intracellular fibroblast Collagen proteome slightly with significant increases in Collagen alpha-1 (VI) and alpha-3 (VI) proteins but only 10-HSA increased levels of Collagen alpha-2 (V), alpha-1 (III), alpha-1 (I) and alpha-2 (I) (all p < 0.05) with the increases being significantly different between 10-HSA and 12-HSA for Collagen alpha-1 (I), collagen-3 (VI) and Collagen alpha-2 (I) (p < 0.01). Collagen type III in ex vivo skin was increased +47% (p < 0.05) by 0.05% (1.7 mM) retinol, +70% (p < 0.01) by 0.01% (0.33 mM) 10-HSA and the combination increased levels by +240% (p < 0.01 for either ingredient).

Conclusion: Chiral (R)-10-HSA has been shown to be superior to 9, 12 and 17-HSA as a PPARα Agonist. Moreover, 10-HSA stimulated Collagen synthesis in monolayer fibroblast culture as assessed by proteomics and immunohistochemically. Furthermore, we also show the synergistic effects of 10-HSA with retinol on Collagen III synthesis in skin explants. These results further highlight the efficacy of 10-HSA as a cosmetically acceptable PPARα Agonist and anti-ageing ingredient.

PPAR; collagen; hydroxystearic acid; proteomics; skin physiology/structure.