Screening and Structure-Activity Relationship for Selective and Potent Anti-Melanogenesis Agents Derived from Species of Mulberry (Genus Morus)

Abstract

Tyrosinase is a multifunctional, copper-containing and rate-limiting oxidase that catalyses crucial steps in the melanogenesis pathway and is responsible for skin-pigmentation abnormalities in mammals. Numerous tyrosinase inhibitors derived from natural and synthetic sources have been identified as an objective for the development of anti-melanogenesis agents. However, due to side effects and lack of expected efficiency, only a small percentage of them are used for medical and cosmetic purposes. This critical review focuses on searching for novel active substances and recently discovered plant-derived anti-tyrosinase inhibitors from the Morus genus (Moraceae family). A detailed analysis of their structure-activity relationships is discussed. The information contained in this article is crucial for the cosmetics and medical industries, in order to show new directions for the effective search for natural anti-melanogenesis products (with satisfactory efficiency and safety) to treat and cure hyperpigmentation.

Keywords: genus Morus; hyperpigmentation; tyrosinase inhibitors; tyrosine.

Figure 1

Process of melanogenesis in human epidermal melanocytes. Symbols: A-phenylalanine hydroxylase, B,C,F tyrosinase, D-glutathione or cysteine, E-tyrosinase related protein-2, G-tyrosinase related protein-1. Arrows in (1A) and (1B) mean position of further polymerization of parent molecule.

Figure 2

Structures of hydroquinone (2), arbutin (3) and kojic acid (4), frequently used as reference standards.

Figure 3

Structures of flavones: norartocarpetin (5), moracenin D (6), kuwanon G (7), kuwanon N (8), kuwanon H (9), 5′-geranyl-5,7,2′,4′-tetrahydroxyflavone (10), cudraflavone (11) and cudraflavone B (12) with tyrosinase inhibitory activity isolated from genus Morus.

Figure 4

Structures of flavanones and flavonones: 7,2′,4′-trihydroxyflavanone (13), steppogenin-7-O-β-D-glucoside (14), steppogenin (15), sanggenon T (16), kuwanon O (17) and kuwanon L (18) with tyrosinase inhibitory activity isolated from genus Morus.

Figure 5

Structures of chalcones: morachalcone A (19), 2,4,2′,4′-tetrahydroxychalcone (20), 3′-[(E)-4″-hydroxymethyl-2″-butenyl]-2,4,2′,4′-tetrahydroxychalcone (21) with tyrosinase inhibitory activity isolated from genus Morus.

Figure 6

Structures of stilbenes: mulberroside A (22), oxyresveratrol (23), oxyresveratrol-3′-O-β-D-glucopyranoside (24), oxyresveratrol-2-O-β-D-glucopyranoside (25) with tyrosinase inhibitory activity isolated from genus Morus.

Figure 7

Structures of benzofurans: moracin C (26), moracin D (27), moracin M (28), moracin N (29), moracin O (30), mulberroside F (31), mulberrofuran G (32), mulberrofuran J (33), moracinoside M (34) with tyrosinase inhibitory activity isolated from genus Morus.