Journal of Clinical and Aesthetic Dermatology

FEB 2018

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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32 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY Feburary 2018 • Volume 11 • Number 2 R E V I E W compared to the hydroquinone group only during the second month of treatment. 2 In a 16-week, baseline-controlled study of 20 patients with Fitzpatrick Skin Types IV to VI, 15% azelaic gel applied twice daily showed a reduction in acne and post-inflammatory hyperpigmentation (PIH). 3 Patients experienced a 2-point improvement according to the investigator's global assessment score. Recently, a controlled trial performed in India studied 60 patients with epidermal melasma. Half of the participants were treated with a glycolic acid peel every three weeks and twice daily 20% AzA cream; the other half was treated with only AzA cream. The AzA/glycolic acid group showed a statistically significant decrease in MASI score compared to the AzA control group 12 weeks onwards. 2 Another controlled trial performed in Poland found that dermocosmetics containing azelaic acid showed improvement in pigmentation measured with a skin colorimeter (Mexameter®, C+K Electronics, Cologne, Germany). Despite these studies, more well-designed clinical trials are still necessary. Additionally, objective methods for the quantifying pigmentation are still lacking, which presents difficulty in evaluating many natural and botanical ingredients. Aloesin. Aloesin is derived from the aloe vera plant and has been shown to inhibit tyrosinase, tyrosine hydroxylase, and dopa oxidase, according to in-vitro studies. Aloesin has direct inhibitory effects on melanogenesis and dose-dependent reductions in melanin content and tyrosinase activity using an in-vitro pigmented skin equivalent. 4 It might even work synergistically with arbutin in vitro. 5,6 Only a single in-vivo study evaluates aloesin's efficacy as a depigmenting agent. 5,6 Choi et al 7 evaluated the inhibitory effect of aloesin on pigmentation induced by ultraviolet radiation (UVR) to the inner forearm. The UV-irradiated regions included a vehicle control group, aloesin treated group, arbutin treated group, and arbutin plus aloesin treated group. Aloesin and arbutin individually and in combination were applied four times daily for 15 days. The authors illustrated a dose-dependent suppression in the aloesin treatment group. This study also supported the synergism between arbutin and aloesin as cotreatment resulted in greater pigmentation suppression than either ingredient alone. 7 These promising results should pave the way for further clinical studies. Mulberry. Mulberry is an extract derived from dried mulberry leaves, Morus alba. In several East Asian countries, the leaves from mulberry trees are used to feed silkworms and have been used in traditional Chinese and Thai medicine in the treatment and prevention of diabetes. 8 According to in-vitro studies, Mulberroside F, mulberry's active component, inhibits tyrosinase activity, melanin formation in melan-cells, melanin transfer, 9 and might serve as a reactive oxygen species (ROS) scavenger. 6,9 To date, there has been one randomized TABLE 1, continued. Summary of clinical studies evaluating the efficacy of natural ingredients as hypopigmenting agents NATURAL INGREDIENTS STUDY HYPOPIGMENTING MECHANISM COMPARISON PIGMENTATION DISORDER CONCLUSION LEVEL OF EVIDENCE* ASCORBIC ACID Single group Efficacy Trial (Kim et al) 56 UVA-mediated catalase inactivation Topical AA with trichloroacetic acid peel vs. trichloroacetic acid peel Severe melasma Melasma peel (alpha-hydroxy acid, AA, and oxygen) showed improvement in 95 percent of patients at eight weeks IIB Controlled trial (Soliman et al) 57 Glutathione depletion, oxidant formation Combined trichloroacetic acid peel and topical ascorbic acid vs. trichloroacetic acid peel Bilateral epidermal melasma According to digital photography and MASI score, combination product showed greater improvement IIA RCT/Split-face (Huh et al) 59 Nitrous oxide production Vitamin C vs. distilled water Melasma After 12 weeks of vitamin C iontophoresis treatment, the colorimeter recorded a clinically significant reduction in luminance value on the treated side IB Single group efficacy Trial (Taylor et al) 60 ROS scavenger, tyrosinase inhibition None Melasma and post-inflammatory hyperpigmentation Novel full-face iontophoresis mask and ascorbyl glucoside preparation over a 1 to 2 month period showed clinical efficacy. *In conjunction to the treatment, patients adhered to a regimen of mandelic/malic acid skin care regimen, broad-spectrum UVA/UVB sunblock, and basic sun protection. IIB *Level of evidence—IA: evidence from meta-analysis of randomized controlled trials; IB: evidence from at least one randomized controlled trial; IIA: evidence from at least one controlled study without randomization; IIB: evidence from at least one other type of clinical study; RCT: randomized controlled trial; UVA: ultraviolet A; UVB: ultraviolet B MASI: Melasma Area Severity Index

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