Human Clinical Trials Using Topical Bakuchiol Formulations for the Treatment of Skin Disorders: A Systematic Review.

BACKGROUND: Bakuchiol is a topical cosmeceutical marketed as a retinoid alternative. Human clinical trial data on bakuchiol’s efficacy for the treatment of dermatologic conditions has not been thoroughly evaluated. OBJECTIVE: To review human clinical trials using topical formulations containing bakuchiol in the treatment of facial skin disorders. MATERIALS AND METHODS: A comprehensive electronic search of Cochrane Library, PubMed, EMBASE, and Web of Science was conducted on August 28, 2022, using the search terms “bakuchiol” and “UP256.” Study characteristics, measured outcomes, significant results, and stated limitations were extracted.  Results: Fifteen human clinical trials were analyzed. Dermatologic conditions treated included aging, acne, and post-inflammatory hyperpigmentation. Twelve trials were unblinded, open-label trials without a control group. Ten trials used a combination therapy containing bakuchiol. Four trials did not specify the dose or concentration of bakuchiol in treatment regimens. The heterogeneity of treatments, study designs, and measured outcomes makes meta-analysis unfeasible.  Conclusion: Trials lack methodologic rigor, which introduces a high risk of bias in reported outcomes. The use of combination topical formulations containing bakuchiol limits the comparison of bakuchiol’s efficacy with retinoids. Continued research with an improved trial design is needed.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7763.

Novel Facial Treatment Regimen Improves Aging Skin Appearance.

BACKGROUND: Skin care regimens with multiple active ingredients offer a multimodal approach to anti-aging treatments. OBJECTIVE: The objective of this research was to investigate the efficacy of a multimodal skincare regimen on facial skin appearance after 12 weeks of twice daily use as compared to baseline. METHOD: 35 healthy female subjects 35–65 years of age of Fitzpatrick skin types I–III with mild to moderate facial photoaging characterized by hyperpigmentation were enrolled. Subjects were seen at baseline, week 6, and week 12, and underwent subject and investigator assessments along with noninvasive evaluations (elasticity, corneometry, dermaspectrophotometer) and photography. RESULTS: Most notable at week 12 was a 60% improvement in smoothness, 82% improvement in dryness, 30% improvement in fine lines, and 24% improvement in crow’s feet. There was an 8% reduction in macule hyperpigmentation (P<0.001) at week 12, supporting excellent pigment lightening qualities for the regimen. There was a statistically significant increase in skin firmness (decrease in elasticity) as early as week 6 of 6% with further improvement observed at week 12 of 16% (P=0.002). SUMMARY: A multimodal skincare regimen with antioxidants, retinol, hydrolyzed pearl, caviar extract, peptides, and growth factors including EGF and TGF-β results in an improvement in the appearance of photoaged skin after 12 weeks of twice daily use. J Drugs Dermatol. 2021;20(3):274-278. doi:10.36849/JDD.5791.

Peptides as Active Ingredients: A Challenge for Cosmeceutical Industry.

Cosmeceutical field, which merges cosmetics and pharmaceuticals, is nowadays a highly investigated research area, because a scientific demonstration of the claimed bioactivity of new cosmeceutical ingredients is increasingly requested. In fact, an aspect differentiating traditional cosmetics from cosmeceuticals is the identification and characterization of the active ingredients and demonstrating its efficacy in the claimed activity. An interesting group of bioactive cosmeceutical ingredients are peptides, which due to their particular properties, meets most of the requirements presented by the cosmeceutical industry when composing new formulas. In this context, beside bioactivity, two additional aspects have been recently considered, when dealing with peptides as cosmeceutical ingredients: bioavailability and stability. We describe herein novel methods applied in order to enhance peptides skin-penetration and stability, reviewing both scientific articles and patents, issued in the cosmeceutical arena.

The Use of Botanical Extracts in East Asia for Treatment of Hyperpigmentation: An Evidenced-Based Review.

Recent years have seen a growth in the Asian cosmeceutical industry and an expanding worldwide marketplace with increasing consumer use of plant-based skin care products. The rising prevalence of Asian cosmeceuticals has led to research studies assessing the safety and efficacy of these products. We seek to review current evidence on safety and efficacy of key ingredients used in Asian cosmeceuticals to treat disorders of hyperpigmentation. A comprehensive search on PubMed was conducted to identify hyperpigmentation-related research studies on eight popular ingredients used in Asian cosmeceuticals: green tea, soy, orchid, licorice, rice water, ginseng, bamboo, and aloe. Both in vitro studies and clinical trials involving human subjects were included. Of the ingredients reviewed, soy and licorice had the most clinical evidence supporting their efficacy, while all other ingredients were supported by in vitro studies. More research is needed to further evaluate the safety and efficacy of Asian cosmeceutical ingredients in treatment of hyperpigmentation. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.4776.

Demonstration of the Antioxidant Capabilities of a Product Formulated With Antioxidants Stabilized in Their Reduced Form

Oxidative damage from reactive oxygen species is instrumental in aging. Topical antioxidants are used in many cosmeceuticals to provide appearance benefits; however, the activity of these antioxidants may be questionable. This research validated the activity of L-ascorbic acid and L-glutathione in the studied facial product and correlated this activity with clinical appearance improvement following 12 weeks of use. J Drugs Dermatol. 2020;19(1):46-49. doi:10.36849/JDD.2020.3947

Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin.

BACKGROUND: Patients with sensitive skin find topical retinoid use for anti-aging purposes challenging due to irritation. Bakuchiol, a meroterpene from the Psoralea corylifolia seed, has retinol functionality through retinol-like regulation of gene expression. OBJECTIVE: This research examined the tolerability, efficacy, and barrier effects of a nature-based bakuchiol-containing cleanser and moisturizer in subjects with sensitive skin. METHODS: 60 female subjects Fitzpatrick skin types I–V age 40–65 years with sensitive mild to moderate photodamaged skin were enrolled in this 4 week study. A sensitive skin panel was constructed: 1/3 eczema/atopic dermatitis, 1/3 rosacea, 1/3 cosmetic intolerance syndrome. Subjects used a nature-based cleanser and moisturizer twice daily and underwent transepidermal water loss (TEWL), corneometry, tolerability assessments, and efficacy assessments at baseline, 5–10 minutes post-application, and week 4. RESULTS: The skin care products were well tolerated and efficacious (P<0.001) in terms of investigator assessed improvement in visual smoothness, tactile smoothness, clarity, radiance, overall appearance, and global anti-aging. Cheek corneometry measurements demonstrated a statistically significant 16% increase in skin moisture content (P<0.001). CONCLUSION: A bakuchiol nature-based anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin.J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5522.

Analysis of spin in the reporting of studies of topical treatments of photoaged skin.

BACKGROUND: Spin-reporting that distorts the interpretation of results-is not unusual within scientific literature. OBJECTIVE: To appraise strategies of spin among placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. METHODS: A systematic review of the literature was performed to identify placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. A survey of spin strategies was developed and applied to the cohort of identified studies. RESULTS: The systematic review led to the identification of 20 studies in which various types of spin strategies, broadly classified as either inappropriate statistical analyses or inappropriate interpretation of results, were used. The most commonly used strategies included use of multiple primary outcomes (95%), inappropriate extrapolation of results from specific outcomes to global improvements (95%), focus on within-group comparisons (75%), and focus on interim analyses to give more weight to nonsignificant findings (65%). LIMITATIONS: Classification of spin strategies was subjective and might not encompass all the methods used in the published literature. CONCLUSION: Findings in this study inform efforts to reduce spin in the dermatologic literature.

Clinical Evidence of Dermal and Epidermal Restructuring from a Biologically Active Growth Factor Serum for Skin Rejuvenation

Background: Topical skin care products use various technologies to promote skin repair. Growth factors of human, animal, and plant-derived origins have clinically demonstrated the ability to repair skin by promoting collagen, elastin, and glycosaminoglycan (GAG) production to reconstruct and reinforce skin's extracellular matrix (ECM). Human skin cells respond to instructions from highly specialized proteins or hormones referred to as growth factors. These growth factors initiate cellular communication that instigates cellular replication, production, or proliferation. The production of elastin and collagen dermal connective fibers slows, and, with age, the regenerative rates of GAGs become delayed. These biological issues can be exacerbated by extrinsic factors such as sun exposure, pollutants, and various other factors. Growth factor-based products have become important topical treatment modalities for addressing signs of skin aging such as fine lines, deep wrinkles, dryness, laxity, and textural irregularities. Objective: The aim of a 12-week clinical trial of a growth factor composition was to assess its effectiveness at restoring skin health through dermal and epidermal restructuring of aged skin. Results: Data from expert grading, and from corneometer and cutometer evaluations, as well as 2D and 3D image analysis, reflected significant improvements in facial skin appearance, firmness, elasticity, and hydration. Elements that improved most dramatically in investigators' assessments included radiance, firmness, tactile elasticity, textural smoothness, overall appearance, and crow's feet. Ultrasound imaging showed continual increases in dermal and epidermal restructuring throughout the study duration. Subject assessments reflected positive product tolerability and positive perception across a broad range of efficacy attributes through 12 weeks of usage. Conclusion: The results verified the ability of a multi-modal plant and enzymatically derived growth factor-based product to achieve skin rejuvenation improvements by stimulating dermal ECM and fibrous tissue regeneration to reduce fine lines and coarse wrinkles, and improve skin firmness and elasticity, while restoring skin to a properly hydrated state. J Drugs Dermatol. 2019;18(3):290-295.

Photoaging and Photoprotection in United States Hispanic Population

Photoaging is a complex and chronic process that induces structural and functional changes in sun-exposed skin, including coarse wrinkles, laxity, dyschromia, telangiectasias, and potential precancerous lesions. Pigmented skin presents different structure and physiology that contribute to distinctive photoaging process. The skin of color population is reported to "age better" than their Caucasian counterparts in general, with fewer wrinkles and better skin texture. However, pigmentary disorders and sun-exposure related dyschromia are highly prevalent in skin of color. Hispanics are the fastest growing population in the U.S. and represents a heterogenous group of people with different skin tones and Fitzpatrick phototypes. They demonstrate large diversity and heterogeneity in skin physiology, pigmentary disorders, and photoaging-related skin color shifting. Specific concerns around hyperpigmentation, skin tone evenness, and texture or roughness are very common among Hispanics, demanding targeted medical and cosmeceutical solutions. Customized daily routines including sufficient photo-protection are essential to address such needs. This mini review identifies some of the specific skin concerns of Hispanics in America and emphasizes the needs for long-term sunscreen use and education. J Drugs Dermatol. 2019;18(3 Suppl):s121-123.

Development of Novel Topical Cosmeceutical Formulations from Nigella sativa L. with Antimicrobial Activity against Acne-Causing Microorganisms.

Acne vulgaris occurs due to the inflammation of sebaceous follicles in the skin. It is triggered by the activity of some bacterial species like Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis. Acquisition of antibiotic resistance by these microorganisms and adverse effects associated with the current treatment regimens necessitate the introduction of novel therapeutic agents for acne vulgaris. Thus, this study was undertaken to develop novel gel formulations from seeds of Nigella sativa L. and to evaluate the antibacterial potential against some acne-causing bacterial species. The antibacterial activity of seed extracts was initially screened against S. aureus and P. acnes by the agar well diffusion method. Thereafter, topical gels were formulated incorporating the ethyl acetate extract of seeds of N. sativa at three different concentrations. These topical formulations were subjected to antimicrobial activity studies while the stability was evaluated over a period of 30 days. All three formulations were capable of inhibiting the growth of S. aureus and P. acnes, with the highest antibacterial activity in the formulation comprising 15% of the seed extract. Interestingly, the antibacterial potency of this formulation against S. aureus surpassed the commercial synthetic product used as the positive control. Moreover, any alteration in color, odor, homogeneity, washability, consistency, and pH was not observed while the antibacterial potency was also retained during the storage period. The potent antibacterial activity in topical gel formulations developed from the ethyl acetate extract of N. sativa signposts their suitability as alternatives to existing antiacne agents in the management of acne vulgaris.

Liposomes of probiotic's lyophilized cell free supernatant; a potential cosmeceutical product.

The potential uses of lyophilized cell free supernatant (CFS) of human oral derived Lactobacillus paracasei SD1 and Lactobacillus rhamnosus SD11 as cosmeceutical ingredients were investigated in the present study. Lyophilized CFS of both strains showed the antioxidant activity in concentration dependent manner. They also exhibited antimicrobial activity against P. acne, S. aureus and S. epidermidis. In combination, these two strains produced synergistic responses, not only on antioxidant activity but also on antimicrobial activity. A liposomal delivery system was employed to mask the unpleasant colour and odour of CFS. The optimal liposome formulation was characterized by a particle size of 344 nm, PDI of 0.19, zeta value of -48.05 mV and %EE of 69.45. The cytotoxicity results showed that the lyophilized CFS, which was toxic, became non-toxic after encapsulating into liposomes. Altogether, current findings demonstrate the worthiness of development of liposomes of probiotic's lyophilized CFS for cosmeceutical applications.

A Prospective Clinical and Instrumental Study on the Effects of a Transcutaneous Cosmeceutical Gel that is Claimed to Produce CO2.

Carboxytherapy is the therapeutic use of carbon dioxide (CO2) in its gaseous state. Since 1933, carboxytherapy has referred to either the subcutaneous injection of CO2 or percutaneous application in a warm bath. The present clinical study was performed to determine if there were any changes in the dermis after the application of a transcutaneous gel, which is claimed to produce CO2, and, if so, how these changes compared to those with CO2 injection. Ten patients received transcutaneous treatment with the gel on one side of the face and the other side without any product was used as a control. We used videocapillaroscopy with an optic probe (VCSO) to evaluate the changes in the microcirculation of the skin. VCSO was performed for the treated right and untreated left ear lobes in each patient. VCSO was performed before treatment was started (VCSO1) and after 7 days of treatment (VCSO2). A comparison of VCSO1 to VCSO2 showed an increase in the microcirculation, an increase in vertical and horizontal capillaries, and a reduction in the area of ischemia. These results are similar to those observed in other studies with CO2 injection. In conclusion, use of this transcutaneous CO2 gel produced changes in the dermis similar to those observed with subcutaneous injection of CO2.

Molecular characterization of glycation-associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations.

BACKGROUND: Glycation is a nonenzymatic reaction that cross-links a sugar molecule and protein macromolecule to form advanced glycation products (AGEs) that are associated with various age-related disorders; thus glycation plays an important role in skin chronological ageing. OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism. METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of Nε -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model. RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress. CONCLUSIONS: The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.

Evidence for Anti-Aging South Korean Cosmeceuticals.

As the market for South Korean skin care products grows in the U.S. and worldwide, consumers will increasingly seek advice from dermatologists regarding their efficacy. In this paper, the evidence behind the anti-aging and skin whitening activity of ingredients in the most popular South Korean skin care products was reviewed and critically evaluated. Industry profit data from Euromonitor was obtained to identify the top cosmeceutical brands by retail value in South Korea. The top selling products and their ingredients were then identified from individual brand websites. A comprehensive literature search was conducted using Pubmed to identify and grade the anti-aging and whitening efficacy for nine popular ingredients: licorice, niacinamide, beta-glucan, snail mucus, ginkgo biloba, ginseng, green tea, pomegranate, and soy. Of the various ingredients reviewed, niacinamide, green tea, licorice, and soy have the most published data for anti-aging and whitening activity. Although the literature shows modest results, small sample sizes limit interpretation. High-level evidence to support the use of South Korean skin care products in anti-aging and skin whitening is lacking.

J Drugs Dermatol. 2017;16(4):358-364.

Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review.

Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, as well as the limitations associated with their use in cosmetic formulations. Hydroxycinnamic acids and their derivatives display antioxidant, anti-collagenase, anti-inflammatory, antimicrobial and anti-tyrosinase activities, as well as ultraviolet (UV) protective effects, suggesting that they can be exploited as anti-aging and anti-inflammatory agents, preservatives and hyperpigmentation-correcting ingredients. Due to their poor stability, easy degradation and oxidation, microencapsulation techniques have been employed for topical application, preventing them from degradation and enabling a sustained release. Based on the above findings, hydroxycinnamic acids present high cosmetic potential, but studies addressing the validation of their benefits in cosmetic formulations are still scarce. Furthermore, studies dealing with skin permeation are scarcely available and need to be conducted in order to predict the topical bioavailability of these compounds after application.

Clinical Assessment of a Novel Jasmonate Cosmeceutical, LR2412-Cx, for the Treatment of Skin Aging.

BACKGROUND: The jasmonates are a novel class of plant-derived anti-aging compounds. Among these, LR2412-Cx (tetrahydrojasmonic acid, Visionnaire) has been demonstrated to reduce photoaging and the appearance of wrinkles, as well as to upregulate collagens, hyaluronic acid and fibrillin. OBJECTIVE: To clinically study the cosmetic effects of a novel jasmonate complex LR2412-Cx in the treatment of visible skin aging. METHODS: LR2412-Cx was evaluated in a 15-subject open-label prospective clinical trial for the treatment of fine wrinkle appearance, texture, and pores. Subjects were evaluated by an investigator at baseline, day 1, day 3, and week 6 with the Alexiades comprehensive grading scale of skin aging, and introducing a novel pore-grading scale and subject quality of life assessments. RESULTS: The mean (SEM) at baseline and at week 6 following twice-daily application were: for the appearance of wrinkles 2.91 (0.12) and 2.70 (0.10); for texture 2.91 (0.10) and 2.55 (0.10); and for pores 3.29 (0.08) and 2.46 (0.09), respectively. The differences in all 3 categories at all follow-up intervals were statistically significant (P<.005). The percentage improvement in investigator-assessed grades relative to baseline at day 1, day 3, and week 6 were: 2.3%, 4.9%, and 7.4% for the appearance of wrinkles, 5.7%, 9.4%, and 12.4% for texture, and 14.2%, 21.6% and 25.2% for pores, respectively. No significant untoward effects were reported. CONCLUSION: Visionnaire LR2412-Cx is a novel jasmonate-containing compound that is safe and effective for the cosmetic treatment of fine wrinkle appearance, texture, and pores of the facial skin.

Superior Efficacy of an Herbal-based Cosmeceutical Compared With Common Prescription and Cosmetic Antiaging Therapies.

INTRODUCTION: Research has shown that a disrupted stratum corneum permeability barrier coupled with chronic inflammation induce signs of extrinsic aging (photoaging). An novel herbal-based three product cosmeceutical regimen used to reverse these two anomalies that does not contain retinol, soy, niacinamide, tea, L-ascorbic acid or esters, hydroxy acids, tocopherol, or growth factors was tested in six human clinical trials to determine effectiveness and safety in reversing photoaging. MATERIALS AND METHODS: Six randomized split face, double blind, prospective, controlled clinical trials involving a total of 110 subjects compared a cosmeceutical blend of novel herbs in regimens consisting of one to three products to several common antiaging topical treatments. These comparative products include prescription tretinoin, physician strength idebenone, kinetin, polyhydroxy, lactic and glycolic acids in reversing signs of photoaging. RESULTS: The novel cosmeceutical blend regimen showed superior efficacy and safety in all six trials. DISCUSSION: These trials substantiate that herbs not used in common antiaging products effectively and safely mitigate and reverse photoaging signs and symptoms. The novel concept of treating photoaging and preventing its progression by repairing and optimizing the stratum corneum barrier, while reversing and inhibiting chronic cutaneous inflammation, has now been proven.

An Approach to Cosmeceuticals.

The cosmeceutical industry is a multi-billion dollar, consumer-driven market. Products promise highly desirable anti-aging benefits, but are not subject to regulation. We present an introduction to cosmeceuticals for the general and cosmetic dermatologist, including definitions and explanations of key terms, an approach to the evidence base, a dissection of chamomile and green tea, two paradigmatic cosmeceutical products, and a window into the underlying psychology of this vast marketplace.

Efficacy and Tolerability of a Skin Brightening/Anti-Aging Cosmeceutical Containing Retinol 0.5%, Niacinamide, Hexylresorcinol, and Resveratrol.

Consumers are increasingly interested in over-the-counter skin care products that can improve the appearance of photodamaged and aging skin. This 10-week, open-label, single- center study enrolled 25 subjects with mild to moderate hyperpigmentation and other clinical stigmata of cutaneous aging including fine lines, sallowness, lack of clarity, and wrinkling. Their mean age was 53.4±7.7 years. The test product contained retinol 0.5% in combination with niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1% in a moisturizing base. Subjects were provided a skin care regimen including a cleanser, hydrating serum, moisturizer, and an SPF 30 sunscreen for daily use. The test product was applied only at night.

The use of this skin brightening/anti-aging cosmeceutical was found to provide statistically significant improvements in all efficacy endpoints by study end. Fine lines, radiance, and smoothness were significantly improved as early as week 2 (P<.001). By week 4, hyperpigmentation, overall skin clarity, evenness of skin tone, and wrinkles showed statistically significant improvement compared to baseline. Mild retinoid dermatitis including flaking and redness occurred early in the study as reflected by tolerability scores. By week 10, subjects reported no stinging, itching, dryness, or tingling.

The results of this open-label clinical study suggest that a topical cream containing retinol 0.5% in combination with niacinamide, resveratrol, and hexylresorcinol is efficacious and tolerable for skin brightening/anti-aging when used with a complementary skin care regimen including SPF 30 sun protection.

J Drugs Dermatol. 2016;15(7):863-868.

Nanotechnology-Based Approaches for Cosmeceutical and Skin Care: A Systematic Review.

Cosmeceuticals have gained great importance and are among the top-selling products used for skin care. Because of changing lifestyles, climate, and increasing pollution, cosmeceuticals are utilized by every individual, thereby making cosmeceuticals a fruitful field for research and the economy. Cosmeceuticals provide incredibly pleasing aesthetic results by fusing the qualities of both cosmetics and medicinal substances. Cosmeceuticals are primarily utilized to improve the appearance of skin by making it smoother, moisturized, and wrinkle-free, in addition to treating dermatological conditions, including photoaging, burns, dandruff, acne, eczema, and erythema. Nanocosmeceuticals are cosmetic products that combine therapeutic effects utilizing nanotechnology, allowing for more precise and effective target-specific delivery of active ingredients, and improving bioavailability.