3 Address all correspondence to Aurachorn Inkanuwat, aurachorn@citu.tu.ac.th Comparative Clinical Evaluation of Centotheca lappacea Extract Cream for Skin Lightening and Tightening Effects in Asian Women: A Randomized, Double-Blind, Controlled Study ORAYA KWANGSUKSTID, WALAIORN PRATCHAYAPRUIT, THAVATCHAI KAMOLTHAM, MONTHAKA TEERACHAISAKUL AND AURACHORN INKANUWAT Department of Medical Services, Institute of Dermatology, Ministry of Public Health, Thailand (O.K., W.P.) College of Allied Health Sciences, Suan Sunundha Rajabaht University, Thailand (T.K.) College of Innovation, Thammasat University, Thailand (A.I.) Department of Thai Traditional and Alternative Medicine, Thai Traditional Medicine Research Institute, Ministry of Public Health, Thailand (M.T.) Accepted for publication November 22, 2021. Synopsis This study evaluated the clinical efficacy of a topical cream containing Centotheca lappacea extract for improving skin color, firmness, and elasticity. Forty-four Asian women aged 30 to 55 with facial melasma were randomly assigned to apply either C lappacea extract cream or a placebo to their face twice daily for 4 weeks. A Mexameter® (Courage + Khazaka Electronic GMBH, Köln, Germany) and Cutometer® (Courage + Khazaka Electronic GMBH, Köln, Germany) were used to measure the melanin index, skin firmness, and skin elasticity at baseline and after 2, 4, and 5 weeks. Clinical side effects and VISIA® (Canfield Scientific, Inc., Parsippany Troy Hills, New Jersey, USA) photographs were evaluated at each clinic visit, and subject satisfaction was evaluated at the end of the study. By week 4, C lappacea extract cream had a significantly stronger melanin reduction effect than the control (12% reduction versus 4.68%, p 0.05). This effect persisted to week 5. Skin firmness and hydration improved significantly in both groups, with no significant differences between groups. The C lappacea extract cream also significantly improved skin resilience (R1) and elasticity (R2 and R5). Both products were well tolerated with no serious adverse effects. INTRODUCTION Skin characteristically loses both structural and functional stability as it ages (1). Structural changes appear in all skin layers and include decreased epidermal thickness, loss of dermal connective tissue, and loss of fat volume. The aging process changes skin’s J. Cosmet. Sci., 73, 3–16 (January/February 2022)

4 JOURNAL OF COSMETIC SCIENCE mechanical properties by leading to skin dryness and roughness, wrinkles, sagging, uneven skin color, and sunspots (2). In women, estrogen deficiency also contributes to aging skin. Maintaining a youthful appearance requires many cosmetic procedures and cosmeceutical products, and research is increasingly focusing on developing innovative anti-aging products derived from natural plant extracts. These products claim to offset the effects of aging however, while anti-aging products should ideally restore dermal connective tissue and epidermal components, the efficacy of most products has not yet been clinically proven. Centotheca lappacea (L) desv., also known as “Ya Hee Yoom” or “Ya Repair,” belongs to the herbal grass family Poaceae (Gramineae) (3). It has long been used in Thailand and other Asian countries to promote postpartum recovery because it is believed to heal wounds and tighten muscles. For example, postpartum women would smoke the treated area by sitting or standing over a wood-fueled fire and burning C lappacea. Asian cultures have also boiled the grass and consumed the resulting juice to promote rejuvenation and anti-aging. The smoke and residue of the dried grass contains compounds such as phenol derivatives and fatty acids (3). Hot water and ethanol extractions of C lappacea produce extracts rich in phenolic and flavonoid compounds, which have antioxidant and anti-inflammatory properties (3,4). C lappacea extracts exhibit mild tyrosinase and collagenase inhibition, similar to the effects of ascorbic acid. Ethanolic C lappacea extracts exhibit higher antioxidant activities than aqueous extracts, with 1.56-fold more 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) scavenging activity and 1.07-fold more lipid peroxidation inhibition activity. The extract also exhibits no cytotoxicity to human skin fibroblasts at concentrations of 0.1–1,000 μg/mL cell viability remains above 90%. Pro MMP-2 inhibition was 21.49 ± 2.60% and active MMP-2 inhibition was 100 ± 0.00% in fibroblasts treated with C lappacea extract, similar to the inhibition efficacy of ascorbic acid. In addition, the extract demonstrated estrogenic activity at 1,000 μg/mL in MCF-7 cells by enhancing cell proliferation by 107.05 ± 17.36% relative to untreated controls (5). Another study found that C lappacea extracts protect against radiation-induced damage to endothelial cells (6). These findings collectively confirm the traditional use of this plant in postpartum women and support its cosmeceutical development as an anti-aging product. Recent studies have evaluated the bioactivity of C lappacea extracts and formulated the extract into a cream for topical use. Maximum antioxidant activity was achieved with 70% C lappacea extract, which resulted in an IC 50 of 56.02 mg/mL and 199.62 mg/mL as determined by DPPH and 2,2’-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid assays, respectively. Furthermore, this concentration showed the highest total phenolic and flavonoid content (0.42 mg gallic acid/g extract and 0.24 mg catechin/g extract, respectively). As a result, 70% C lappacea extract was evaluated for anti-tyrosinase and anti-collagenase activities. 70% C lappacea extract inhibited collagenase activity with an IC 50 of 30.78 mg/ mL, but the IC 50 for anti-tyrosinase activity could not be determined. The stability of 70% C lappacea extract was determined by comparing initial antioxidant activity, as measured with the DPPH assay, to antioxidant activity after 3 months of storage at 4, 25, and 40°C. Antioxidant activity was not significantly reduced, regardless of the storage temperature. Cream containing 70% C lappacea extract at a final concentration of 0.5% was stable at all storage conditions (7). Despite their potential promise, C lappacea extract-based creams have not yet been tested in clinical trials. This study therefore aimed to evaluate the efficacy of a new facial cream