# Skin Depigmenting Agents in Anti-Aging Cosmetics: A Medicinal Perspective on Emerging Ingredients
## 3 Results and Discussion
### Medicinal Chemistry Perspective of New Skin Depignetting Ingredients in Anti-Aging Products
#### 3.2.2 Bakuchiol  
Bakuchiol is a monoterpene isolated from the seeds of _Psoralea corylifolia_ [PERSON], a plant widely used in China and India to treat a variety of diseases [31]. The wide range of biological activities previously demonstrated by bakuchiol rendered this ingredient a leading candidate for drug development [31]. Bakuchiol has recently emerged as a trendy ingredient in cosmetic skincare products, claiming to have similar efficacy to over-the-counter vitamin A derivative products [32]. In fact, although no structural similarity is observed, bakuchiol has recently been recognized as a \"functional analogue of retinol\" [33], being in some instances even considered a \"natural substitute\" of retinol with less undesirable effects [34]. Although bakuchiol is currently used in cosmetic skincare products, only a few studies have been reported in early 2019 and recently reviewed proving its significant efficacy in reducing the signs of skin aging [12, 32, 33, 34]. Its depigmenting efficacy was shown in two clinical studies using creams containing 0.5% bakuchiol, with good tolerability, and these findings are attributed to bakuchiol's ability to block both \(\alpha\)-melanocyte-stimulating hormone (\(\alpha\)-MSH) and tyrosinase activation [12, 33]. In mammals, \(\alpha\)-MSH is required for the development of pigmentation, by binding to its specific melanocortin-1 receptor and by increasing cyclic adenosine monophosphate. Melanogenesis is induced by strongly upregulating the expression of melanogenic enzymes such as tyrosinase. Due to the emergence of bakuchiol in the skincare market, several studies have recently been performed to highlight its relevant usage in a variety of cosmetic products beyond anti-aging products, such as formulations for sensitive skin. A study with a bakuchiol anti-aging cleanser and moisturizer for sensitive skin examined the tolerability, efficacy, and barrier effects in subjects with sensitive skin [35]. The analyzed skincare products were well tolerated and effective in terms of visual smoothness, tactile smoothness, clarity, radiance, and overall appearance [35]. Other studies evaluated the in vitro efficacy of a serum combining bakuchiol and _Vanilla tahitensis_ extract in the prevention of skin photoaging [36]. Results showed a good safety profile and clinical anti-aging efficacy, reducing ptosis, and increasing skin firmness and radiance. Regarding photoprotection, the combination of both ingredients demonstrated synergistic protection against IL-8 and p16 overexpression [36]. A related study developed by the same authors demonstrated a positive synergy to fight against the signs of skin aging by combining both of these ingredients [37]. The topical use of this combination was assessed in normal human dermal fibroblasts obtained from healthy donors. The treatment of fibroblasts with vanilla extract or bakuchiol, or their combination, resulted in the prevention of morphologicalchanges induced by UVA exposure, indicating a potential activity of these compounds towards the prevention and/or reduction of wrinkles, to firm the skin, and/or restart epidermal and dermal cell activity [37]. Additionally, this association prevented the senescence of UVA-related cells, allowing them to revive the activity of epidermal and dermal cells [37]. A clinical study developed to assess the anti-aging efficacy and safety of a new night facial serum combining melatonin with bakuchiol and ascorbyl tetraisopalmitate in all skin types was also recently reported [38]. The efficacy, safety, and general properties of the serum were assessed in 103 subjects, and after 12 weeks of clinical evaluation, the serum showed a significant decrease in wrinkles (11%), an increase in skin firmness (8%), a reduction in redness (70%), and an overall improvement in skin quality and complex-ion [38]. Additionally, hydration levels increased significantly and transepidermal water loss significantly decreased [38].