ber of sunburn cells and epidermal Langerhans cells damaged by UV radiation. With the emerging popularity of green tea extractformulated skin care products, more clinical trials are needed to evaluate the lightening effects of green tea on human skin.
Licorice
Licorice, also known as Glycyrrhiza glabra, has long been used for its medicinal value and anti-inflammatory components.25,26,27 However, licorice also contains the active ingredient Glabridin that may have value in reducing pigmentation. Glabridin works by inhibiting UVB-induced pigmentation and tyrosinase, thus disrupting the pathway of pigment production.28 In vitro studies have shown that Glabridin has 16 times the skin lightening effects of hydroquinone, a known skin lightening agent.28,29 In line with this, in a single-center, double-blind clinical study of 18 subjects comparing the efficacy of a hydroquinone-free formula, containing Glabridin, there was a significant reductions in ultraviolet-induced hyperpigmentation when compared to both the negative control as well as 4% hydroquinone cream.30 Furthermore, in a single-blinded study comparing the efficacy of belides, embilica, and licorice 7% to 2% hydroquinone in the treatment of melasma, the degree of depigmentation in both groups was not statistically different.31 Another active ingredient present in licorice, liquirtrin, has also demonstrated depigmention properties. In fact, in one double-blind, split-face study of 20 subjects comparing 2% and 4% liquirtin to 4% hydroquinone for the management of melasma, both concentrations of liquirtin were significantly more effective in decreasing pigmentation when compared to hydroquinone.32
Orchid
Orchid extract contains plant pigments called anthocyanins, a group of phytochemicals known for their antioxidant and antiinflammatory properties.33 These flavonoids combat reactive oxygen species (ROS) and are capable of soothing and enhancing skin tone while minimizing oxidative stress.33,34 In vitro studies suggest that orchid extract is effective in suppressing WNT1 expression by downregulating a transcriptional activator of the gene.35 Increased expression of WNT1 stimulates melanocyte stem cell differentiation. A double-bind, comparative, split-face clinical trial in 48 female patients with melasma and/ or solar lentigines to evaluate the in vivo efficacy of a cosmetic formulation containing orchid extract compared to 3% vitamin C derivative.36 After 8 weeks of topical use, the orchid extract group showed similar efficacy as vitamin C group in lightening melasma and lentigines by colorimetric measurements and subjective questionnaire. Importantly, the study found little risk associated with the use of topical orchid extract. No instances of contact dermatitis, pruritis, or irritation were reported during the 8 weeks of treatment.
Rice Water
Rice (Oryza sativa) extract is a key ingredient in many Asian hair and skin treatments.37 It contains high levels of bioactive phenolic compounds (p-coumaric, ferulic, and caffeic acids) that display anti-tyrosinase and photoprotective properties.38 The anti-melanogenic peptides found in rice bran protein were shown to significantly inhibit melanogenesis in mouse B16 melanoma cells without causing cytotoxity.39 The suppression of melanogenesis can be attributed to its anti-tyrosinase and TRP-2 inhibitory effects, which protect the cell from oxidative stress in a dose-dependent manner. It is proposed that the potent skin lightening effects of the extract result from the synergistic activities of the active phenolic ingredients.38 A double-blind randomized control trial of 24 volunteers demonstrated that rice extract cream (0.1% or 0.2% ) resulted in a significant decrease in melanin index (P< 0.001) post-treatment (28 days) compared to baseline.38 Furthermore, no subjects reported adverse effects over the study period. To confirm the safety of the topical treatment, patch testing in a separate cohort of 25 healthy subjects showed no signs of skin irritation on exposure to rice extract cream. Another clinical trial using semi-purified rice bran extract entrapped in niosomes formations demonstrated skin lightening in 30 human subjects within a 28-day period.40 Both gel and cream formulations resulted in a sustained skin lightening effect post-treatment even after continued application was forgone for 7 days. No skin irritation was noted in this clinical study.
Soy
Soybean is a legume commonly grown in East Asia.41 It consists of many biologically active ingredients including isoflavones.42 There are a number of in vitro studies attesting to the pigmentreducing properties of soybean extract.42,43,44 Equally significant is the large amount of clinical trials supporting its efficacy as skin lightening agent. A 16-week, double-blind, placebo-controlled clinical study of African-American, Hispanic, and Asian patients with Fitzpatrick skin types III–V showed that a soy-containing topical formulation resulted in a reduction in post-inflammatory hyperpigmentation caused by acne. Assessments of acne severity and hyperpigmentation were measured by expert clinical evaluations, global acne asessments, and spectroscopic measurements evaluating changes in redness and melanin over time.46 Another double-blind, vehicle-controlled study enrolled 65 women with facial photodamage and monitored their skin condition over a 12-week period with the use of a soy extractcontaining moisturizer.47 Using colorimetric measurements, digital photography, and clinical evaluation, the soy moisturizer was significantly more efficacious in reducing mottled pigmentation blotchiness and overall skin tone compared to the vehicle. No adverse events were reported. In a study of 16 Hispanic women with melasma, subjects applied a stabilized soy extract once daily for 3 months to areas of dyspigmentation with untreated dyspigmented areas serving as controls.47,48 Fourteen of the sixteen subjects had a 12% reduction in hyperpigmentation as measured by colorimetric evaluations. No side effects were noted. In fair-complexioned men of Celtic origin,
Licorice
Licorice, also known as Glycyrrhiza glabra, has long been used for its medicinal value and anti-inflammatory components.25,26,27 However, licorice also contains the active ingredient Glabridin that may have value in reducing pigmentation. Glabridin works by inhibiting UVB-induced pigmentation and tyrosinase, thus disrupting the pathway of pigment production.28 In vitro studies have shown that Glabridin has 16 times the skin lightening effects of hydroquinone, a known skin lightening agent.28,29 In line with this, in a single-center, double-blind clinical study of 18 subjects comparing the efficacy of a hydroquinone-free formula, containing Glabridin, there was a significant reductions in ultraviolet-induced hyperpigmentation when compared to both the negative control as well as 4% hydroquinone cream.30 Furthermore, in a single-blinded study comparing the efficacy of belides, embilica, and licorice 7% to 2% hydroquinone in the treatment of melasma, the degree of depigmentation in both groups was not statistically different.31 Another active ingredient present in licorice, liquirtrin, has also demonstrated depigmention properties. In fact, in one double-blind, split-face study of 20 subjects comparing 2% and 4% liquirtin to 4% hydroquinone for the management of melasma, both concentrations of liquirtin were significantly more effective in decreasing pigmentation when compared to hydroquinone.32
Orchid
Orchid extract contains plant pigments called anthocyanins, a group of phytochemicals known for their antioxidant and antiinflammatory properties.33 These flavonoids combat reactive oxygen species (ROS) and are capable of soothing and enhancing skin tone while minimizing oxidative stress.33,34 In vitro studies suggest that orchid extract is effective in suppressing WNT1 expression by downregulating a transcriptional activator of the gene.35 Increased expression of WNT1 stimulates melanocyte stem cell differentiation. A double-bind, comparative, split-face clinical trial in 48 female patients with melasma and/ or solar lentigines to evaluate the in vivo efficacy of a cosmetic formulation containing orchid extract compared to 3% vitamin C derivative.36 After 8 weeks of topical use, the orchid extract group showed similar efficacy as vitamin C group in lightening melasma and lentigines by colorimetric measurements and subjective questionnaire. Importantly, the study found little risk associated with the use of topical orchid extract. No instances of contact dermatitis, pruritis, or irritation were reported during the 8 weeks of treatment.
Rice Water
Rice (Oryza sativa) extract is a key ingredient in many Asian hair and skin treatments.37 It contains high levels of bioactive phenolic compounds (p-coumaric, ferulic, and caffeic acids) that display anti-tyrosinase and photoprotective properties.38 The anti-melanogenic peptides found in rice bran protein were shown to significantly inhibit melanogenesis in mouse B16 melanoma cells without causing cytotoxity.39 The suppression of melanogenesis can be attributed to its anti-tyrosinase and TRP-2 inhibitory effects, which protect the cell from oxidative stress in a dose-dependent manner. It is proposed that the potent skin lightening effects of the extract result from the synergistic activities of the active phenolic ingredients.38 A double-blind randomized control trial of 24 volunteers demonstrated that rice extract cream (0.1% or 0.2% ) resulted in a significant decrease in melanin index (P< 0.001) post-treatment (28 days) compared to baseline.38 Furthermore, no subjects reported adverse effects over the study period. To confirm the safety of the topical treatment, patch testing in a separate cohort of 25 healthy subjects showed no signs of skin irritation on exposure to rice extract cream. Another clinical trial using semi-purified rice bran extract entrapped in niosomes formations demonstrated skin lightening in 30 human subjects within a 28-day period.40 Both gel and cream formulations resulted in a sustained skin lightening effect post-treatment even after continued application was forgone for 7 days. No skin irritation was noted in this clinical study.
Soy
Soybean is a legume commonly grown in East Asia.41 It consists of many biologically active ingredients including isoflavones.42 There are a number of in vitro studies attesting to the pigmentreducing properties of soybean extract.42,43,44 Equally significant is the large amount of clinical trials supporting its efficacy as skin lightening agent. A 16-week, double-blind, placebo-controlled clinical study of African-American, Hispanic, and Asian patients with Fitzpatrick skin types III–V showed that a soy-containing topical formulation resulted in a reduction in post-inflammatory hyperpigmentation caused by acne. Assessments of acne severity and hyperpigmentation were measured by expert clinical evaluations, global acne asessments, and spectroscopic measurements evaluating changes in redness and melanin over time.46 Another double-blind, vehicle-controlled study enrolled 65 women with facial photodamage and monitored their skin condition over a 12-week period with the use of a soy extractcontaining moisturizer.47 Using colorimetric measurements, digital photography, and clinical evaluation, the soy moisturizer was significantly more efficacious in reducing mottled pigmentation blotchiness and overall skin tone compared to the vehicle. No adverse events were reported. In a study of 16 Hispanic women with melasma, subjects applied a stabilized soy extract once daily for 3 months to areas of dyspigmentation with untreated dyspigmented areas serving as controls.47,48 Fourteen of the sixteen subjects had a 12% reduction in hyperpigmentation as measured by colorimetric evaluations. No side effects were noted. In fair-complexioned men of Celtic origin,
