Retinoids

Retinoids include both naturally occurring forms of vitamin A (such as retinol, retinal, and retinoic acid) and synthetic versions. They are powerful anti-aging agents, with retinol and its metabolites (retinal, tretinoin, isotretinoin, and alitretinoin) being among the most effective. These first-generation retinoids are fat-soluble, allowing retinol to penetrate the outer skin layer and slightly enter the dermis. Inside keratinocytes, retinol binds to specific receptors, stimulating the activity of skin cells such as keratinocytes, fibroblasts, melanocytes, and Langerhans cells. This interaction boosts cell proliferation, enhances the skin’s protective barrier, minimizes water loss through the skin, protects collagen from breakdown, and inhibits enzymes that degrade the skin’s structural matrix [7].

Published research suggests that tretinoin, incorporated into regulated medicinal products, stands out as the retinoid with the most robust evidence supporting its anti-aging effects, including its efficacy in reducing wrinkles and counteracting photoaging [8].

Despite advancements in retinoid formulations, their use continues to be hindered by several adverse effects, including skin irritation, dryness, peeling, redness, and a burning sensation. These negative reactions frequently lead to patients stopping their use, highlighting the urgent need for the development of better retinoid compounds. Ideally, these new compounds would mimic the gene expression patterns of retinol, delivering its beneficial effects without the associated unwanted side effects. Increasing evidence suggests that bakuchiol may offer this retinol-like functionality, presenting a promising alternative in skincare treatments [9].

Bakuchiol

Bakuchiol, a distinctive meroterpene phenol sourced extensively from the Psoralea corylifolia plant, is quickly becoming a prominent figure in the cosmeceutical landscape due to its compelling range of properties. To date, around 100 bioactive compounds have been extracted from P. corylifolia, with the most significant ones categorized under coumarins, flavonoids, and meroterpenoids [10]. Bakuchiol is a key member of the meroterpenoids class of natural compounds. The plant from which it is derived, Psoralea corylifolia, is extensively utilized in traditional Indian (Ayurvedic) and Chinese medicine for a broad spectrum of ailments. The seeds of this plant have been commonly employed in the treatment of various skin conditions such as psoriasis, leukoderma, leprosy, and acne, as well as inflammatory diseases of the skin. Additionally, they have been used for their aphrodisiac, anthelmintic (anti-parasitic), laxative, and diuretic properties [11]. Recognized for its potential in anti-aging applications, bakuchiol effectively addresses signs of skin aging by diminishing wrinkles and enhancing skin elasticity. Moreover, its anti-inflammatory attributes are known to soothe skin inflammation, making it beneficial for treating conditions such as acne and redness. Additionally, its antibacterial capabilities offer protection against harmful bacteria, contributing to healthier skin. This combination of effects marks bakuchiol as a versatile and valuable agent in skincare formulations, signaling its rising importance in both dermatological treatment and everyday skincare routine [12].

The benefits of bakuchiol include evening out the skin tone, causing no irritation or adverse reactions, and being safe for twice-daily use. It is suitable for all skin types, helps soothe and heal the skin, reduces the appearance of fine lines, and accelerates cell regeneration [13].

It is worth mentioning that bakuchiol is currently the subject of extensive research due to its complex nature that is yet to be fully understood. For instance, bakusylan (bakuchiol salicylate) represents an innovative compound created by combining bakuchiol with salicylic acid. This fusion aims to develop a new category of functional retinoids that offer superior skin advantages. Studies suggest that bakusylan may provide better skin penetration through the stratum corneum, boost the expression of type IV collagen genes in skin models that include both epidermal and dermal components, and promote collagen production in cultures of adult human dermal fibroblasts [14].

Comparison of the Effects of Retinoids and Bakuchiol

In a clinical trial that compared the effects of retinol and bakuchiol [15], it was found that both substances significantly decreased the area affected by fine facial wrinkles relative to the baseline measurements. Additionally, clinical assessments revealed that participants using bakuchiol experienced greater improvements in hyperpigmentation compared to those using retinol. Both treatments were effective in reducing the intensity of pigmentation and the affected area. Interestingly, it is notable that participants in the retinol group experienced significantly more skin scaling at every follow-up appointment. This indicates that bakuchiol matches retinol in its capacity to ameliorate signs of photoaging, while being better tolerated by the skin. Hence, bakuchiol emerges as a promising and more tolerable alternative to retinol. Further research, particularly long-term studies, is essential to fully understand the trade-offs between increased application frequency and reduced side effects, especially since the observed results with bakuchiol required twice-daily application. This study indicates that bakuchiol could be a feasible choice for patients interested in natural treatment options [16].

In a comparative study between retinol and bakuchiol [17], researchers explored their antioxidative and anti-inflammatory effects, including their impact on cell activation, and their role in the development of extracellular matrix (ECM) components and skin renewal processes. This research found that bakuchiol not only shares several functional properties with retinol yet also offers distinctive, advantageous traits. Using bakuchiol as a treatment method introduces a comprehensive, multi-faceted approach to combating skin aging. It functions as an antioxidant, reduces inflammation, stimulates cell activity, enhances the production of vital ECM components, and promotes the repair and rejuvenation of the epidermis.

Bakuchiol matches retinol’s effectiveness in regulating gene expression, with a significantly improved tolerance profile compared to retinoids. Moreover, it may be used without the need to gradually increase the dose. Its photostability also simplifies its incorporation into skincare products. Additionally, bakuchiol does not lead to phototoxicity, so there is no mandatory requirement for sunscreen use when applying it, unlike retinoid treatments [18].

Interestingly, research indicates that the anti-photoaging properties of retinal are amplified when it is paired with natural retinol-like substances such as bakuchiol. Remarkably, this combination enhances retinal’s effectiveness without compromising its safety profile [19]. It is also worth noting that bakuchiol possesses unique antioxidant properties that retinol lacks, enabling it to engage a different mechanism of action. The effectiveness of antioxidants is often maximized when they are used together, due to their synergistic effects. This synergy was evident in research findings where bakuchiol proved to be more effective in photoprotection when used in conjunction with other antioxidants, underscoring its enhanced and synergistic capabilities [20].

It is also important to note bakuchiol’s potential for treating acne. Research shows that bakuchiol shows promise as a new agent that may complement and enhance the effectiveness of currently available anti-acne formulations. Bakuchiol is likely the only agent after retinoic acid shown to be effective against multiple pathophysiologic features of acne [21].

Statement of Human and Animal Rights

All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 2008 revision of the Declaration of Helsinki of 1975.