Your skin colour comes from a natural pigment called melanin, which in turn, is synthesized in specialized cytoplasmic organelles called melanosomes. Within the melanosome, the enzymatic conversion of the amino acid tyrosine to melanin is catalyzed by the enzyme tyrosinase. The melanosomes in the darker areas of the skin are more active than those found in other areas. Overactive melanosomes can also cause visible hyperpigmentation on the skin such as age spots, melasma, and other types of discolorations.
THE 14 POSSIBLE PATHWAYS OF SKIN LIGHTENING ARE:
- Preventing maturation or intra-cellular trafficking of tyrosinase is a way to reduce the effect of the enzyme on pigmentation. This is done by influencing tyrosinase mRNA and also mRNA of other tyrosinase-related proteins (TRP-1 &dopachrome tautomerase (TRP-2) or MITF (microphtalmia transcription factor)
E.g.: Grape seed extract
- Protease activated receptor 2 (PAR-2) is important for melanosomal transfer from melanocytes to keratinocytes.
E.g.: Octadecenedioic acid (Vitamin D) binds to PPAR-2 to reduce melanogenesis.
- Melanocytes express high levels of sAPP (soluble N-terminal ectodomain of the beta-amyloid precursor protein). sAPP plays an important role in release of melanin particles via dendritic tips. Blocking the sAPP signalling is another way to influence melanosome transport.
E.g.: Vitamin B-3 (Niacinamide)
- Enzymatic degradation of melanin in keratinocytes to avoid UVB induced pigmentation
- Reduction of ROS (reactive oxygen species)prevents activation of melanogenesis.
E.g.: Antioxidants, curcumin, grapeseed extract.
- Vitamin C, vitamin E and cystine reduce UVB induced pigmentation
- Melanogenesis is also induced by inflammatory mediators (IL-1alpha & TNF-alpha). Inhibition of these causes skin lightening.
E.g.: Mulberry, curcumin
- Various pathways can be induced by signalling through bFGF (basic fibroblast growth factor), HGF (hepatocyte growth factor), SCF (stem cell factor), ET-1 (endothelin-1), ACTH (adrenocorticotropic hormone), alpha-MSH(alpha-melanocyte stimulating hormone) via their respective receptors present on melanocytes.
- Endothelin-1 induction of pigmentation in melanocyte can be prevented by 3’antisense S-oligo for tyrosinase that also reduces UV induced pigmentation
- Wnt/beta-catenin pathway is known to play a role in development process of melanin. Binding of Wnt proteins can be inhibited by dikkopf (DKK1), a factor secreted by fibroblasts which suppresses growth of melanocytes and strongly inhibits melanin production.
- Bone morphogenic protein (BMP) is involved in modulating melanogenesis, since melanocytes express BMP receptors and produce BMP-4 that is able to decrease melanin synthesis.
- Extracellular signal-regulated kinase (ERK) is stimulated by bFGF, HGF, SCF. Ceramides inhibit melanogenesis by activation of ERK which down regulates MITF.
- Ceramides are important as they cause glycosylation of lipids and sorts melanogenic proteins to melanosomes.
- DNJ (1-deoxynojirimycin), which is a glycosidase inhibitor and the main ingredient of mulberry leaves, effects lipid glycosylation which inturn, inhibits melanin synthesis.