Often in this column, several species within a family might be discussed in relation to a broad range of health benefits. Licorice and mushrooms are good examples. In this case, and in this column, the focus will be on several species within a family that are thought to confer the same type of dermatologic benefit. The Morus genus within the Moraceae family appears to include several species that display skin-lightening properties.

Tyrosinase is the enzyme that controls the production of melanin. Suppressing tyrosinase activity to achieve skin lightening is a well-established method in dermatologic practice. The desire for products with fewer side effects than the mainstay, hydroquinone, or natural products such as kojic acid or arbutin, has led to investigations of several species in the Moraceae family. Notably, several Moraceae trees have been found to exhibit antioxidant activity (Int. J. Mol. Sci. 2012;13:2472-80; Biol. Pharm. Bull. 2002;25:1045-8; Biosci. Biotechnol. Biochem. 2010;74:2385-95; J. Pharm. Pharmacol. 2004;56:1291-8). The focus here, though, will be on the skin-lightening activity of various parts of Morus (commonly known as mulberry) trees.

In 2013, Singh et al. assessed the effects of mulberry, kiwi, and Sophora extracts on melanogenesis and melanin transfer in human melanocytes and in cocultures with phototype-matched normal adult epidermal keratinocytes. The extracts were evaluated against isobutylmethylxanthine, hydroquinone, vitamin C, and niacinamide. The investigators found that compared with unstimulated control, mulberry, kiwi, and Sophora extracts significantly reduced melanogenesis in normal adult epidermal melanocytes and human melanoma cells. Melanin transfer also was lowered, as was filopodia expression on melanocytes. The authors concluded that the test compounds compared well with standard-bearing depigmenting agents and warrant consideration as topical agents for diminishing hyperpigmentation (Exp. Dermatol. 2013;22:67-9).

Encouraging results in melasma treatment

A randomized, single-blind, placebo-controlled trial of 50 Filipino patients (49 women, 1 man) to examine the safety and efficacy of 75% Morus alba (white mulberry) extract oil was conducted by Alvin et al. in 2011. Patients were evaluated at weeks 4 and 8. The Melasma Area and Severity Index (MASI) score, Mexameter score, and Melasma Quality of Life (MelasQOL) score were measured, with the mulberry extract group performing significantly better than the placebo group according to all metrics.

The 25 patients treated with mulberry extract showed improvement in the MASI score, from 4.076 at baseline to 2.884 at week 8 (mean difference, 1.19); the mean difference for the placebo group was 0.06. The mean Mexameter reading revealed a significant difference, with a slight increase for the mulberry group (indicating lighter pigmentation), and the placebo group scored a slightly higher value. In addition, the MelasQOL score for the mulberry group improved markedly from baseline to week 8 (58.84 to 44.16), whereas the placebo group score improved only slightly, from 57.44 at baseline to 54.28 at week 8.

Adverse events were rare, with mild itching in 4 patients reported from the mulberry group, and 12 cases of either itching or erythema reported by the placebo group.

The investigators concluded that 75% mulberry extract oil objectively diminishes the hyperpigmentation of melasma in skin types III-V, although they recommend additional research with a larger sample size and longer treatment duration and follow-up (J. Drugs Dermatol. 2011;10:1025-31).

Paper mulberry

The bark of paper mulberry (Broussonetia papyrifera, also known as Morus papyrifera) is composed of extremely strong fibers used to produce high-quality paper and cloth. In China, the leaves, stem, leaf juice, roots, fruits, and bark have all been found to impart various health benefits, with the stem and leaf juice used to treat skin disorders and insect bites (Phytother. Res. 2012;26:1-10).

In one study, a 0.4% concentration of paper mulberry extract was demonstrated to suppress tyrosinase activity by 50% compared with 5.5% hydroquinone and 10% kojic acid. Notably, paper mulberry is not considered a significant irritant even at 1% concentration (J. Drugs Dermatol. 2009;8:s5-9).

White mulberry

In 2002, Lee et al. investigated the in vitro effects of an 85% methanol extract of dried white mulberry leaves on melanin biosynthesis. They found that one of the primary bioactive constituents, mulberroside F (moracin M-6, 3’-di-O-beta-D-glucopyranoside), inhibited the tyrosinase activity that converts dopa to dopachrome in the melanin synthesis process and also suppressed the melanin formation of melan-a cells. In addition, the mulberry extract inhibited tyrosinase activity more potently than did kojic acid (Biol. Pharm. Bull. 2002;25:1045-8).

The following year, a different team found that the young twigs of white mulberry also suppressed tyrosinase activity as well as melanin production in B-16 melanoma cells. In vivo, the extracts decreased melanin synthesis in a guinea pig model without displaying toxicity (J. Cosmet. Sci. 2003;54:133-42).


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