Fig. 13.1
Aloe vera
Fig. 13.2
Rumex occidentalis
Fig. 13.3
Bearberry
13.2.1 Aloe Vera
Aloe vera is a succulent perennial herb (Fig. 13.1) which is probably native to North Africa but now found in the tropics and warmer areas of the world, including Asia. Viscous, transparent liquid can readily be extracted from the pea green fresh leaves. Some uses described in traditional medicine include minor wounds and burns [4].
Aloesin is a pigment-inhibiting substance derived from aloe vera extract. The study by Choi et al showed that aloesin prevents UV-induced pigment development in the skin of healthy volunteers. The results demonstrated that pigmentation suppression of aloesin was significantly greater than control but less than arbutin. However, aloesin used together with arbutin afforded more pigment suppression than arbutin alone. This study supports the current use of aloesin in nonprescription cosmeceutical formulations [5].
13.2.2 Rumex Occidentalis
Rumex occidentalis is a perennial herb (Fig. 13.2) found in North America, Asia, and Europe. It is a small, leafy plant with narrow leaves [6]. Rumex occidentalis is a traditional remedy, used as a mild laxative, digestive aid, and liver cleanser. Topical preparations can relieve insect stings [7].
A randomized double-blind study by Mendoza et al showed that Rumex occidentalis 3 % extract in cream formulation has lightening efficacy equivalent to hydroquinone 4 %. This study was conducted in 45 Filipino women who were randomized to receive placebo, hydroquinone 4 %, and Rumex occidentalis 3 % cream [8].
13.2.3 Bearberry
Bearberry is an evergreen shrub (Fig. 13.3) that usually grows less than 6 inches tall. The leaves are alternately on the branches and the flowers are white to pink and bear round. Bearberry is native to Labrador, Alaska, Virginia, Illinois, Nebraska and New Mexico [9].
13.3 Antioxidants/Free Radical Scavengers/Photoprotective Agents
Under this category are the following botanicals: orchids, proanthocyanidin from grape seed extract, procyanidin from maritime pine bark, coffeeberry, green tree extracts from Camellia sinensis, licorice (Glycyrrhiza glabra), mulberry (Morus alba), soy, and umbelliferone from carrots (Figs. 13.4, 13.5, 13.6, 13.7, 13.8, 13.9, 13.10, 13.11, and 13.12, respectively).
Fig. 13.4
Orchid
Fig. 13.5
Grape seed
Fig. 13.6
Maritime pine bark
Fig. 13.7
Coffeeberry
Fig. 13.8
Camellia sinensis
Fig. 13.9
Glycyrrhiza glabra
Fig. 13.10
Morus alba
Fig. 13.11
Soybean
Fig. 13.12
Daucus carota sativus
13.3.1 Orchids
Orchids are perennial herbs widely distributed mostly in tropical and subtropical forests. While there is much variability in the specialized structures of the Orchidaceae family, the flowers are characteristic, having three petals and three petallike sepals, with a conspicuous central sepal forming a lip (labellum) (Fig. 13.4) [13].
Tadakoro et al conducted a split face study comparing orchid extract cream and vitamin C 3 % cream. Results obtained using the melanin index, clinical evaluation, and skin color tone scale were equivalent for orchid extract and vitamin C at the end of the study [14].
13.3.2 Flavonoids
Flavonoids are a group of naturally occurring substances in fruits, vegetables, plant parts, tea and wine. Diversity in their basic phenolic structure is the basis for their grouping and variations in physiologic activities [15, 16]. The main groups of flavonoids are flavones, flavanones, catechins, and anthocyanins [16]. While flavones and anthocyanins are found in berries and grapes, flavanones are sourced from citrus peels and fruits, and catechins are derived from red wine and tea. Several mechanisms have been found in vitro, such as nitric oxide inhibition, leukocyte immobilization, and arachidonic acid metabolism inhibition [16]. Their pigment inhibitory action rests on the antioxidant activity, tyrosinase inhibition and DOPA oxidation [2].
13.3.2.1 Grape Seed Extract
Grapes are climbing shrubs native to different parts of the world, especially in the tropical, subtropical and some temperate regions. The principal genera are Cissus, Parthenocissus, Ampelopsis and Vitis [17]. Proanthocyanidin is an antioxidant extracted from grape seeds (Fig. 13.5) [17].
Yamakoshi et al found that intake of the powder form containing 81.0 % proanthocyanidin (GravinolTM) has a beneficial effect on melasma. Eleven patients completed an open-label study for 12 months. Outcomes documented, using colorimetry and melanin index, showed significant improvement in terms of lightening and decrease in lesion size [18].
13.3.2.2 Procyanidin
Procyanidins present in apples, maritime pine bark (Fig. 13.6), cinnamon, aronia fruit, cocoa beans, and grape seeds and skin are flavonoids with high antioxidant properties in vitro [19]. They have been shown to modulate the arachidonic acid pathway, inhibit gene transcription and protein expression of inflammatory mediators, and hence have anti-inflammatory effects [20]. Pinus pinaster (French maritime pine), growing in low-lying coastal plains, is found in France, Spain and Portugal [21].
Handog et al conducted a randomized, double-blind, single-center trial to determine the lightening efficacy of tablets containing 24 mg of procyanidin, 6 mg of β-carotene, 60 mg of ascorbic acid, and 15 IU of D-α-tocopherol acetate. After 8 weeks, it was shown that the melanin content decreased significantly among the treatment patients (p < 0.0001). MASI also decreased for both the treatment and placebo groups (p < 0.001) with a greater decline noted among the treatment group (p < 0.0001) [22].
13.3.3 Pycnogenol
Pycnogenol is a dietary supplement with many purported uses. Despite the insufficient evidence for benefit in any chronic condition [23], it remains available in over the counter formulations. Pycnogenol has been reported to have antioxidant and anti-inflammatory properties [24]. Its oral formulation at 50–200 mg per day has been used for a variety of conditions such as chronic venous insufficiency, diabetes, hypertension and retinopathy [24].
For melasma, the recommended dose was 75 mg/day [24]. Ni et al gave 30 women 75 mg of pycnogenol daily. At the end of the thirty-day study, they noted an average decrease in melasma area of 25.86 ± 20.39 mm (p < 0.001). They also noted an average decrease in pigmentary intensity of 0.47 ± 0.51 unit (p < 0.001) [25]. Twenty-nine patients with melasma were given 100 mg of daily pycnogenol by Campos et al. Two months of treatment yielded 26–50 % improvement by blind observation verified by digital photography [26]. In another study assessing the preventive action of pycnogenol to IPL-induced melasma-like pigmentation, Campos et al gave 100 mg of daily pycnogenol to 25 patients after three sessions of IPL. None developed melasma-like pigmentation in the treatment arm, while two developed pigmentation in the control group [27].
13.3.4 Coffeeberry
Coffea arabica is one of the two main species of coffee cultivated today, which accounts for 75–80 % of the world’s production [28]. It grows best in subtropical and equatorial regions. Coffeeberry extract (Fig. 13.7) is naturally rich in polyphenol antioxidants, specifically cholorogenic acid, condensed proanthocyanidins, quinic acid, and ferrulic acid [29].
McDaniel in 2010 enrolled 30 females with moderate photoaging to determine the beneficial effects of coffee berry extract 1 % for photoaging, including pigmentation. His 6-week protocol included 20 full face and 10 split face participants. The full face participants applied the active product, while split face participants applied the active product on one side of the face and the vehicle on the opposite side. Blinded evaluations were done by dermatologists. Full face participants showed 27 % improvement in global assessment, 16 % for fine lines and wrinkles, 18 % for roughness and dryness, and 25 % for pigment. In the split-face study, notably greater improvement was noted on the active product than vehicle [29].
13.3.5 Green Tea Extracts
Green tea extracts come from Camellia sinensis (Fig. 13.8), cultivated in China for the past 3000 years. Polyphenolic compounds from green tea extracts act as anti-inflammatory, antioxidant, and anticarcinogenic. Its antioxidant and in vitro tyrosinase inhibition that may be responsible for its lightening effect [30].
No et al showed that green tea extracts inhibited mushroom tyrosinase in vitro [31].
13.3.6 Licorice
Glycyrrhiza glabra (Fig. 13.9), commonly known as licorice, is a perennial herb belonging to the pea and bean family, native to Eurasia, Northern Africa, and Western Asia. It grows about 1 meter tall with leaflets arranged in pairs along a central axis and light-blue to violet flowers held in loose conical spires [32]. Licorice extract has several pigment inhibitory mechanisms to wit, melanin dispersal, melanin biosynthesis inhibition, and cyclooxygenase inhibition [2].
Glabridin, a polyphenolic flavonoid serving as the main component of the extract, has been shown to prevent UVB-induced hyperpigmentation. It also has anti-inflammatory activity by inhibition of superoxide anion and cyclooxygenase [33]. Liquiritin, another component, has been reported to affect melanin dispersability and epidermal removal [34].
Alobaidi et al conducted a randomized double-blind study among 100 volunteer female patients with melasma. The 28-day study revealed a 93 % improvement of melasma in the group treated with Glycyrrhiza glabra 2.5 % cream, while only 4 % improvement was shown among the placebo group. The difference in proportion of improved patients was statistically significant (p value: 0.001) [35].
13.3.7 Mulberry
Morus alba (Fig. 13.10), also known as white mulberry, is native to China but is now found in most of the USA [36]. White mulberry is a perennial shrub or tree that can grow as high as 15 meters. The leaves are alternate and ovate, while flowers maybe staminate or pistillate. Fruits can be white, black or purple.
Lee et al measured the tyrosinase and superoxide inhibition of mulberry extract in vitro. Eighty-five percent of methanol extract of dried mulberry leaves was utilized for the experiment. Mushroom and mammalian tyrosinase assays were used to determine tyrosinase inhibition and Oyanagui method for superoxide suppression. In the mushroom tyrosinase assay, inhibition was expressed as IC50, the concentration of sample that inhibits 50 % of tyrosinase activity. Strong inhibitory activity for tyrosinase was shown with IC50 of 0.29 ug/ml. Mammalian tyrosinase was suppressed to 50 % at a concentration of 68.3 ug/ml. Superoxide inhibition was 8.3 % at100 ug/mL. Mulberry extract’s tyrosinase inhibition was 4.5 times more potent than kojic acid in mushroom assay with similar results in the mammalian assay [37].
13.3.8 Soy
Soybean is an annual legume of the Fabaceae family (Fig. 13.11), cultivated mainly for its vegetable protein and processed into food and industrial products. Its origin is believed to be from a wild plant in East Asia. It is now grown in most parts of the world, with the largest producers being the USA, Brazil, and China. It is an erect branching plant, which can grow to more than 2 meters. Flowers can be white or a shade of purple. Edible seeds contained in pods can be yellow, green, brown, black or bicolored [38]. Major components of soy reported to be responsible for its pigment inhibitory activity are the protease inhibitors and isoflavones. Protease inhibitors decrease PAR-2 activation, inhibiting melanosome transfer [39]. Isoflavones decrease melanogenesis by inhibiting DOPA oxidase activity [40].
Female patients with Fitzpatrick phototype I–III were enrolled in the study of Wallo et al, evaluating the benefits of soy-containing moisturizer for photoaging. This parallel, randomized, double-blind, vehicle-controlled study lasted for 12 weeks. It was shown that soy moisturizer was significantly better than vehicle (P value < 0.05) as to mottled pigmentation, blotchiness, dullness, fine lines, overall texture, overall skin tone, and overall appearance [41].