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Summary. Phytochemicals: Mechanisms of Action is the latest volume in a highly regarded series that addresses the roles of phytochemicals in disease.
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This review examines the latest clinical studies using plant-derived compounds and their effectiveness in the management of hyperpigmentation disorders. Keywords: phytochemicals, botanical, hyperpigmentation, melasma, lentigines. Hyperpigmentation is a common dermatologic condition among patients of all skin types. Pigmentation disorders are the third most common among dermatologic disorders and cause significant psychosocial impairment.

These disorders and damages caused by ultraviolet UV light are generally difficult to treat and a variety of products exist ranging from prescription, over-the-counter, to cosmeceuticals. The gold standard topical treatment for hyperpigmentation is hydroquinone, a hydroxyphenolic chemical. The search for novel lightening agents has led to the investigation of natural plant extracts.

Phytochemicals—God’s Endowment of Curative Power in Plants

Many of the active plant compounds may be more potent inhibitors of melanin formation than hydroquinone and may not be associated with the same cytotoxicity. Cosmeceuticals are topical cosmetic—pharmaceutical hybrids 5 containing biologically active ingredients that may have a beneficial effect due to possible pharmacological actions that may improve the appearance of the skin and are increasingly popular alternatives to standard depigmenting agents.

Accurate advice on the benefits, side effects, and indications requires evidence-based knowledge. Note: Data from Fisk et al 8 and Zhu and Gao. In April , we searched EMBASE and Medline databases for published clinical studies examining the use of plant-derived products for the treatment of hyperpigmentation.


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Studies involving plant-derived compounds and pigmentation as an outcome measure were included. Bibliographies were searched for additional studies that met the inclusion criteria. Of the articles, ten unique studies met the inclusion criteria Table 1. Aleosin is a moderately high molecular weight glycoprotein obtained from the Aloe vera plant. Additionally, it has a greater affinity for the DOPA oxidase catalytic site on tyrosinase in comparison to other botanicals such as arbutin and kojic acid. On the basis of these findings, Choi et al 15 examined the inhibitory effect of aleosin treatment on the pigmentation of human skin induced by UV radiation.

Aleosin treatment was found to inhibit hyperpigmentation after UV radiation in a dose-dependent manner. Reduction in pigmentation was objectively measured with a colorimeter. With new drug delivery technology, there may be ways to study how enhancement of penetration may or may not affect its function as a depigmenting agent. Alpha-bisabolol is a monocyclic sesquiterpene alcohol and the primary constituent of the Matricaria chamomilla plant.

The compound has multiple properties, including anti-inflammatory, analgesic, antibiotic, and gastric protective agent.

Phytochemicals in the treatment of hyperpigmentation

Given the in vitro studies, Lee et al 16 evaluated the impact of alpha-bisabolol on hyperpigmented skin in a double-blind, vehicle-controlled trial. Over a 2-month period, 28 Korean female subjects, aged 32—52 years, used 0. With the assistance of a spectrophotometer as an objective measuring tool, the authors observed a stronger whitening effect in comparison to the vehicle control.

Based on the in vitro and in vivo skin studies, alpha-bisabolol may be utilized as an adjunctive therapy for the reduction of hyperpigmentation.


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  7. The naturally occurring glucopyranoside acts to inhibit melanosomal tyrosinase and 5,6-dihydroxyindolecarboxylic acid polymerase activities at noncytotoxic concentrations. Subsequently, the authors conducted a week double-blind clinical trial treating 50 postmenopausal females with solar lentigines using topical deoxyarbutin. For the assessment of improvement in solar lentigines, digital images were obtained, coded using a 0—4 comparative scale , and evaluated side-by-side by three independent expert judges.

    The study resulted in a slight reduction in the overall skin lightness and improvement of solar lentigines in a population of light-skinned and dark-skinned individuals. Ellagic acid EA is a polyphenol phytochemical that can be found in certain plants in nature and in some nutrients such as green tea, strawberry, geranium, grapes, cherries, and walnuts.

    Results of in vitro experiments have indicated that EA suppresses melanogenesis by inhibiting tyrosinase activity. This inhibition is caused by chelation of the copper atoms on the tyrosinase molecules. Glabridin, an active ingredient in licorice extract derived from Glycyrrhiza glabra exerts an anti-inflammatory effect via inhibition of superoxide anion production and cyclooxygenase activity. The study analyzed depigmentation with a colorimeter and in a subsequent process through histochemical analysis of the number of melanocytes.

    The authors concluded that glabridin inhibits tyrosinase activity but has no effect on DNA synthesis. Hesperidin is the predominant flavonoid derived from the peel and membranes of citrus fruits. Flavonoids are naturally occurring phenolic phytochemicals that have been reported to possess a host of biological properties in vitro.

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    More recent studies have found that hesperidin induces melanogenesis in murine melanoma cells when added to the culture medium, which, if extrapolated to in vivo conditions, would lead to hyperpigmentation. Both these results suggest that hesperidin may increase melanin in human skin. Regardless, clinical studies are needed to assess its response in humans. An active compound of licorice, liquiritin has been evaluated in two clinical studies.

    Some patients used sunscreen while others did not, a variable not considered in the analysis of the results.

    Phytochemicals: Mechanisms of Action (Volume 4)

    Nevertheless, the results are similar to another study by Amer and Metwalli 29 from Egypt. The size of the lesions was measured directly using a millimeter grid scale. Additionally, clinical and photographic evaluation was performed and the overall response was rated on a scale of excellent, good, fair, or poor.

    A promising therapeutic option in the treatment of pigmentation disorders is oral procyanidin, which is the main active component of Pinus pinaster bark extract. Procyanidin is known to have both antioxidant and anti-inflammatory properties but only a few published trials have been conducted regarding the potential benefits of oral procyanidin in melasma.

    Handog et al conducted a double-blind, placebo-controlled prospective study involving 30 healthy female subjects treated with procyanidin for 30 days. Changes in pigmentation were measured using a Mexameter, the Melasma Area and Severity Index, and a global evaluation by the patient and investigator. The study showed significant improvement in the degree of lightening of melasma in the treatment group. Mexameter measurements demonstrated a significant decrease in the degree of pigmentation, suggesting that procyanidin with vitamins A, C, and E is safe and well tolerated, with minimal adverse events.

    However, the isolated effects of procyanidin remain unknown and further experimentation is needed. Silymarin is a standardized extract derived from the milk thistle plant Silybum marianum and is a natural polyphenolic flavonoid. Silybin is a biologically active component with antioxidant properties. Furthermore, Western blot analysis indicated that silymarin decreased the expression of tyrosinase protein. This study suggests that silymarin may be useful as a natural skin-lightening agent. Given the previous findings, Altaei 34 sought to assess the safety and efficacy of topical silymarin cream at two different doses in a double-blind, placebo-controlled study for treatment of 96 melasma patients.

    Both the silymarin creams were reported to reduce the Melasma Area and Severity Index score to 0, although the photographs shown in the manuscript did not have photographs that were standardized for lighting. Clinical trials testing the safety and efficacy of multiple botanicals revealed that patients had fewer adverse effects in comparison to gold standard therapies.

    Serious adverse events, such as toxic epidermal necrolysis, 37 are rarely reported and occur more frequently with oral and high concentration formulations. Treating hyperpigmentation poses a challenge to many physicians and an expanded arsenal is necessary to aid in the improvement of topical treatments. A large variety of safe and effective skin-lightening botanicals exist as potential alternatives to current products, such as, hydroquinone Figure 2. Natural extracts represent a large repository of ingredients for skin-lightening cosmeceuticals.

    Further studies that integrate phytochemicals with standard therapies are needed for the treatment of hyperpigmentation. Dermatologists and primary-care physicians would benefit from familiarizing themselves with the evidence supporting or refuting the use of botanically derived products for hyperpigmentation treatment, as patients are becoming increasingly interested in natural alternatives. Ethnic skin disorders overview. J Am Acad Dermatol. Treatment of hyperpigmentation.

    The Benefits of Phytochemicals

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