464 JOURNAL OF COSMETIC SCIENCE
been shown to induce the expression of genes related to the pathway of retinoids in vitro,
promotes activities such as skin regeneration, enhances ECM proteins, and boosts cellular
resistance to oxidative stress, all while minimizing the skin inflammation associated with
retinoids similarly to bakuchiol. In vivo, the ingredient helped to minimize the appearance
of wrinkles, homogenized the skin tone, and reduced the number of dark spots.
Treatment with S rebaudiana extract increased retinol binding protein (RBP1) gene
expression by 18.2% in a statistically significant manner (data not shown), which improves
the amount of retinol entering the cell. Therefore, the combination of the extract with
retinol can reduce the use of retinol in formulations to minimize potential adverse effects.
Moreover, as shown in Figure 12, the active ingredient also enhanced the expression of
nuclear receptors RAR and RXR with similar efficacy to retinoic acid, which triggers the
transcriptional activity of retinoid-responsive genes that impart the final benefits.
To determine if S rebaudiana extract can deliver benefits similar to retinoids, several
end points were measured. As shown in Figure 13, S rebaudiana extract increased the
production of the HAS2 gene, similarly to retinoic acid, which potentially leads to an
Figure 9. (A) Percentage of variation in MBNL1 levels. Data shown as MEAN ± SEM of the mean of three
independent experiments. Statistical significance: *p 0.05, ***p 0.001, calculated using an unpaired
student’s t-test. (B) Representative images showing MBNL1 (green) protein in fibroblasts after tetrapeptide-1
treatment and after microcurrent stimulation (1000 µA, 70 mV/mm, 1 hour).

465 DELIVERING SUSTAINABLE SOLUTIONS TO IMPROVE WELLBEING
enhanced production of hyaluronic acid in the skin and not only increases skin hydration
but also promotes many healing aspects and tissue remodeling. S rebaudiana extract was
also shown to stimulate skin renewal and repair as it boosted HB-EGF, a member of the
family of epidermal growth factors required for re-epithelialization processes. These results
suggest that S rebaudiana extract is involved in skin regeneration.
To further prove the retinoid-like efficacy, the ability of S rebaudiana extract to regulate
dermis remodeling was tested. S rebaudiana extract behaved similarly to retinoic acid
(Figure 14) as the collagen and elastin levels were boosted and MMPs were reduced, which
helps preserve the dermis for a rejuvenating effect.
Finally, to provide additional confirmation of retinoid-like efficacy, the extract’s ability to
boost the antioxidant response of skin cells was tested (Figure 15). S rebaudiana extract
increased the expression of HMOX1 by 954%, the expression of TXNRD1 by 209%,
and the expression of oxidative stress induced growth inhibitor 1 (OSGIN1) by 261%,
respectively. These genes are involved in cellular protection against oxidative stress,
detoxification of reactive oxygen species, and redox signaling.
Figure 10. (A) Percentage of EDA-fibronectin levels shown as MEAN ± SEM of the mean of four independent
experiments. Statistical significance: **p 0.01, ****p 0.0001, calculated using an unpaired student’s
t-test. (B) Representative images of EDA-fibronectin marker (green) and nuclei (blue) after tetrapeptide-1
treatment and after microcurrent stimulation (1000 µA, 70 mv/mm, 1 hour).