13 COMPARATIVE CLINICAL EVALUATION OF C LAPPACEA SAFETY MONITORING All subjects completed the study, with 9% of subjects (2/22) from the C lappacea group and 22% (5/22) from the control group reporting some degree of intolerance during their first use of the products. However, the intolerance was mild and disappeared spontaneously without recurrence by the second application. No rashes, skin redness, exfoliation, or increased acne were observed during the product application period. SUBJECT SATISFACTION All subjects completed a satisfaction questionnaire. 100% of subjects in the C lappacea group and 95% of subjects in the control group appreciated the organoleptic characteristics and efficacy of the treatment. In addition, all subjects reported that they would like to continue using the product and will recommend the product to a friend. 91% of C lappacea subjects and 100% of control subjects were willing to purchase the cream at the end of the study. RESULTS AND DISCUSSION This is the first clinical study to demonstrate the efficacy and tolerability of a new facial cream formulated using C lappacea extract. Objective measurements taken with a Mexameter® (Courage + Khazaka Electronic GMBH, Köln, Germany) demonstrated that the C lappacea extract cream provided significantly better skin lightening effects than the control cream after 4 weeks of use. In addition, C lappacea extract cream had significant skin lightening effects on both melasma and normal skin relative to baseline. The extent of skin lightening was satisfactory and was clinically evident in some subjects. Based on Mexameter® (Courage + Khazaka Electronic GMBH, Köln, Germany) results from other studies (12,13), the skin lightening effects of C lappacea extract cream could be observed much earlier than the effects of standard skin lightening agents such as hydroquinone. The clinical response to 2–5% hydroquinone becomes evident only after 5–7 weeks, and therapy may be continued for 3–12 months (14). The skin lightening effects of C lappacea extract cream could be related to the antioxidant, anti-inflammatory, and tyrosinase inhibition properties of C lappacea (3,4). Based on the steps of melanogenesis, there are three potential mechanisms of action for natural and chemical skin lightening agents: (1) regulation of melanin synthesis, (2) interference with melanosome maturation and transfer, and (3) transepidermal melanin elimination (15). Many flavonoids plant extracts regulate melanogenesis by directly inhibiting tyrosinase or acting on the other parts of melanin synthesis pathway (15–17). Antioxidant and anti- inflammatory activities of these natural plants can also affect the melanin regulation pathway (15). Moreover, anti-inflammatory activity would theoretically help decrease skin redness following an inflammatory mechanism. In this study, the C lappacea extract cream caused steady pigment reduction throughout the 4 weeks of treatment, whereas subjects using the control cream showed worsening of pigmentation by the end of treatment. Several studies have reported the worsening of pigmentation as a side effect of melasma treatment, mostly in individuals with darker skin color and high sun exposure (14,18–20). Using a high concentration of topical lightening

14 JOURNAL OF COSMETIC SCIENCE agents may also cause skin irritation, which aggravates pigment darkening (21,22). All subjects in this study used the same face cleanser and sunscreen to control for the effects of differing photoprotection. Furthermore, this study was conducted during the rainy season, thus reducing the amount of natural sun exposure. The best explanations for the worsening of pigmentation observed mainly in the control group are therefore either natural differences in individual treatment responses or the difference between the control and treatment products (i.e., C lappacea extract). Measurements of skin biomechanical properties taken using a Cutometer® (Courage + Khazaka Electronic GMBH, Köln, Germany) provide information on skin distensibility, viscoelasticity, and recovery. Numerous studies have characterized these properties in relation to health (9) and aging (22–26) and have assessed variation over time caused by active pharmaceutical, cosmetic, or topical products (27). Young, healthy skin is resilient (R1 i.e., can return to its original position following deformation), highly elastic (R2, R5, and R7), and exhibits minimal fatigue (R4) (11). In contrast, aging skin is less resilient (increased R1). Several studies have reported a negative correlation between age and skin elasticity parameters (R2, R5, and R7) and therefore recommend these parameters for evaluating skin aging (8,24,28). R2 and R7 are better for characterizing skin elasticity than R5 because they also account for the viscous part of the skin deformation (9). Ryu et al. (8) reported that R7 measurements from the cheek, upper arm (sun-exposed site), and back (nonexposed site) are significantly correlated with the age of healthy adults, suggesting that R7 is valuable for measuring changes in skin elasticity. In this study, C lappacea extract cream significantly enhanced skin resilience and elasticity after 4 weeks of treatment, as gains in skin resilience (R1) and gross elasticity (R2) were significant in the treatment group but not the control. However, there was no significant change in R7 in either group. Both groups showed a significant increase in R6 (Uv/Ue) relative to baseline after 2 weeks of treatment. According to previous research on the relationship between skin elasticity and skin moisture (29), the increased R6 in this study suggests improved epidermal hydration, which may be due to the hydrating effect of the tested products. The C lappacea extract cream was well tolerated by most subjects throughout the 4 weeks of application. Although some subjective irritation was reported following the first use of the products, this irritation was mild, transient, and not clinically evident. All subjects appreciated the organoleptic characteristics of the tested products. The results of this study suggest that the C lappacea extract cream restores both the epidermal and dermal components of skin, which is the desired effect of anti-aging products. This study was intentionally short (4 weeks) to demonstrate the rapidity of the treatment effects however, further studies using a longer treatment duration could help to determine the full effectiveness of C lappacea extract cream. CONCLUSIONS This study showed that skin cream containing C lappacea extract is effective for pigment reduction, enhanced epidermal hydration, improved skin resilience, and increased skin elasticity after 4 weeks of application. The product was well tolerated by all subjects in this study, who experienced no serious adverse events and were 100% satisfied with the treatment results.