Study Finds SME Enhances Skin Hydration and Reduces Wrinkles

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Retinol and other Vitamin A derivatives are widely regarded as effective antiaging ingredients due to their proven ability to reduce wrinkles, promote keratinocyte proliferation, enhance epidermal barrier function, and protect collagen.¹ However, retinol's use is often accompanied by skin irritation, dryness, and reduced consumer tolerance, which are attributed to its interaction with retinoic acid receptors (RAR).² As a result, alternatives like bakuchiol have been introduced, offering improved tolerability but with limitations in efficacy and safety concerns due to their molecular structure.³

Milk thistle (silybum marianum), with its active ingredient silybin, has emerged as a promising alternative, known for its antioxidant, anti-inflammatory, and DNA-protective properties.⁴ However, its low water solubility and poor skin affinity limit its bioavailability. To address these challenges, a silybin-encapsulated liposomal formulation (SME) was developed to enhance stability and skin interaction. A recent study evaluated the antiaging efficacy and safety of SME compared to retinol and bakuchiol through in vitro, ex vivo, and clinical testing, with the goal of positioning SME as a competitive, well-tolerated ingredient in skincare formulations.⁵

Materials and Methods

In vitro, ex vivo, and in vivo methods were used to test the skin efficacy of Retinol 50C (50% retinol in polysorbate 20), bakuchiol, and SME (Silybin Phytosome Extract). RARɣ binding assays were conducted using coactivator recruitment and TR-FRET methods with purified human recombinant receptors. Antioxidant activity was assessed in keratinocytes, measuring oxidative stress via the DCFH-DA probe. Ex vivo treatments of human skin explants with retinol (0.1%), bakuchiol (0.2%), and SME (0.8%) were analyzed for collagen and hyaluronic acid content using Sirius Red and HABP immunofluorescence. A clinical study was conducted with 57 volunteers aged 45 to 73, applying formulations twice daily for56 days. Wrinkle depth, skin redness, and hydration were measured using Visia CR2.3, AEVA-HE, SIAscope, and Corneometer devices. Statistical analyses, including t-tests and nonparametric tests, were performed, with significance defined as p < 0.05.

Results

The study found SME exhibited a significantly safer and more effective profile than retinol and bakuchiol across various parameters. In RARɣ activation assays, researchers found SME showed minimal activation compared to retinol, which caused excessive activation, and bakuchiol, which had moderate activation. This suggested that SME is less likely to trigger the adverse events typically associated with retinoid use. In vitro, researchers found that SME effectively reduced reactive oxygen species (ROS) production in a dose-dependent manner, achieving results comparable to the positive control, resveratrol, without cytotoxicity. Bakuchiol, on the other hand, exhibited toxicity at higher concentrations. Ex vivo, they stated that SME increased both collagen I and collagen III levels, improving the skin's collagen profile, which is indicative of youthful skin. Bakuchiol, in contrast, reduced collagen I levels. The study found SME also promoted hyaluronic acid production, providing a hydrating benefit similar to retinol but without its negative effects. Clinical trials corroborated these results, showing that SME significantly reduced wrinkle thickness, particularly in the periorbital area and across the face, outperforming both bakuchiol and retinol. Additionally, SME was the only treatment found to significantly improve hydration in vivo and demonstrated superior skin tolerance, with no reports of irritation or redness, unlike retinol and bakuchiol, which caused some adverse reactions.

Conclusions

The study highlights SME as a promising antiaging ingredient, offering a distinct mechanism of action and superior safety profile compared to retinol and bakuchiol. Researchers stated SME’s minimal activation of RARɣ, ability to reduce ROS production, enhance collagen synthesis, stimulate hyaluronic acid production, and improve skin hydration demonstrate its potential in addressing multiple signs of aging. Furthermore, the study wrote SME's excellent clinical performance, including significant reductions in wrinkle thickness and enhanced hydration, along with its superior skin tolerance, positions it as a safer and more effective alternative to traditional antiaging ingredients. These findings suggest that SME could be a valuable addition to cosmetic formulations aimed at improving the appearance and health of aging skin.

References

1. Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019;36(4):392-397. doi:10.5114/ada.2019.87443
2. Duell EA, Aström A, Griffiths CE, et al. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro. J Clin Invest. 1992;90(4):1269-1274. doi:10.1172/JCI115990
3. Dhaliwal S, Rybak I, Ellis SR, et al. Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing. Br J Dermatol. 2019;180(2):289-296. doi:10.1111/bjd.16918
4. Yoo HG, Jung SN, Hwang YS, et al. Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. Int J Mol Med. 2004;13(1):81-86.
5. Boira C, Chapuis E, Lapierre L, et al. Silybum marianum extract: A highly effective natural alternative to retinoids to prevent skin aging without side effects. J Cosmet Dermatol. Published online December 18, 2024. doi:10.1111/jocd.16613