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To beautify the skin, i.e. reduce evidence of age spots, darkened areas of pigmentation, is of great concern to many. An even skin tone is considered by most cultures to be beautiful. How to safely achieve even skin tone for sun damaged skin is more difficult. Skin beauty is a personal journey and the stigma attached to skin lightening is often not considered. The experts on what constitute beautiful skin are the ones in the mirror's reflection. Healthy skin, is generally considered to be even in tone, of smooth texture, unlined and without acne. Many of the natural skin lightening ingredients also contain cross over action in other mechanism due to the complexity of the chemical composition inherent to several of the known plant extract lighteners. While they are effective at skin lightening, they remain effective antioxidants. Whether dark skinned or light skinned, even skin tone remains a desirable aspect of beauty. While many wish to lighten their skin tone, others are trying to go darker. That which constitutes beauty, lies in the eyes of the beholder, even if that remains the self.
As the end user of any lotion, milk , serum, cream, it is the individual experience that determines the efficacy or not thereof. DIY / homemade lotions, bath body wash and serums are made with the goal to lighten the skin, in hopes that pigment will disappear or old age spots likewise. Can this be done safely and without irritation or allergic reactions? Drugstores and big name labels sell lotions that claim to lighten the skin, however the concentrations of the active components are unknown. They may also be in a base that causes allergic reaction, where as the active itself may not. Some actives are inherently unstable, and by the time they reach the consumer, they are of little use. Safest and most effective are not necessarily mutually exclusive when it comes to skin lightening. Safest generally requires longer treatment time.
To improve the efficacy of a skin whitening treatment or regime, it is prudent not to play games with chemicals that are proven to cause permanent damage when it can readily be avoided. Several plant extracts contain effective chemicals for lightening pigmentation and the research has greatly refined the understanding of the mechanisms of action over the years. It remains prudent to keep in mind that not each individual will have the same success,. It would be nice to guarantee the efficacy of a product however far too many variables come into play. The type of oil used to make a homemade/ DIY lotion due to the palmitic acid content can undo the positive effect of the lightening chemical component/ extract. As the consumer knowledge base continues to increase, producers are forced to meet the demand. Unfortunately due to restrictions in various jurisdictions for health and safety concerns, truly effective formulas are not necessarily readily available.
Understanding the pigmentation pathway as currently known is useful prior to examining the various skin-lightening compounds and the assosciated mechanisms of action. Skin color is determined by both the type and quantity of melanin synthesized by the melanocyte and its distribution pattern in the epidermis. The formation of melanin is through a series of oxidative reactions involving the amino acid tyrosine and the enzyme tyrosinase.
Most critical is the first reaction as the reaction sequence that follows proceeds spontaneously at physiological pH. At this point in the sequence, tyrosinase converts tyrosine to dihydroxyphenylalanine (DOPA) and subsequently to dopaquinone. Thereafter, dopaquinone is converted to dopachrome through auto-oxidation, and, finally, to dihydroxyindole or dihydroxyindole-2-carboxylic acid (DHICA) to form eumelanin (black-brown pigment= darken the skin). The latter reaction occurs in the presence of dopachrome tautomerase and DHICA oxidase. In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl DOPA or glutathione DOPA. The latter results in the formation of pheomelanin, a yellow-red pigment. ( influences skin tone )
Tyrosinase regulates melanin synthesis in melanocytic cells. It is a membrane-bound copper containing glycoprotein, and the critical rate-limiting enzyme of melanin production. Tyrosinase is produced only by melanocytic cells, post its synthesis it is further processed in the ER and Golgi. After processing it is transported to melanosomes, where the pigment is synthesized and deposited. Melanosomes are transferred from melanocytes to neighboring keratinocytes and are distributed in the skin and hair to produce visible color. An excess of melanin or abnormal distribution can cause irregular pigementation and hyperpigmentation of the skin. Developing effective therapies to treat disorders of pigementation, disruption of tyrosinase activity is the usual target. Several approaches exist to decreases tyrosinase activity i.e. competitive or non-competitive inhibition of tyrosinase catalytic activity, disruption of tyrosinase maturation or by reduce its stability. Manipulation of tyrosinase levels include modulating of tyrosinase messenger RNA (mRNA) transcription and its post-transcriptional stability or reducing its potential for synthesis at the gene expression level.
Before treating hyperigmentation the etiology must first be elucidated. It is not always clear as there are many factors that influence hyperpigmentation: 1) photo sensitizing agents, 2) hormone imbalance, 3) UV exposure, 4) Systemic disease, 5) drug interactions. etc.
Hydroquinone:
A variety of topical treatments have been developed and some with exceptional effect. The current Gold Standard is the use of Hydroquinone (HQ) . HQ is considered to be one of the most effective in vivo and in vitro inhbitors of melanogensis which causes a reversible inhibition by affecting both DNA and RNA synthesis. The unfortunate aspect is that while it is effective at inhibiting melanocytes it remains cytotoxic to the surrounding cellular structures and leads to degeneration of both collagen and elastin fibers. Inappropriate usage may lead to darkening of the skin. Care must be taken when using potent lightening agents.
Tyrosinase Inhibitors:
There are a variety of effective inhibitors however they are not true inhibitors of tryosinase, rather they act to interfere with the production of melanin. L ascorbic acid is one such molecule. It acts to to reduce o-dopaquinone to dopa, avoiding dopachrome and melanin formation. AA2G is also shown to be particularly effective for those that cannot tolerate the low pH requirement of LAA.
Phenolic compounds are another broad category of which many have been isolated and found to be effective. These enzyme substrates show good affinity for the binding site on tyrosinase and result in a reduction in the formation of dopachrome. Some act as cheltors of copper which also acts to inhibit enzymatic activity via destabilization of tyrosinase.
Acids or bases also act as inactivators of tyrosinase. These act to denature the enzyme, leaving it non functional and as such, inhibit activity.
Suicide substrates are another class of inhibitors and more correctly true inhibitors. These act to bind tyrosinase irreversibly. These inhibitors are catalyzed by tyrosinase forming covalent bonds and inducing the enzyme catalyzing "suicide reaction."
True inhibitors are of four types. 1) competitive inhibitors, 2) noncompetitive inhibitors, 3) mixed (competitive/non-competitive) inhibitors, and 4) non-competitive inhibitors.
1. Competitive inhibitor: a substance that combines with a free enzyme in a manner that prevents substrate binding. That is, the inhibitor and the substrate are mutually exclusive, often because of true competition for the same site.
2. Non competitive inhibitors: can bind only to the enzyme-substrate complex.
3. Mixed (Competitive/ Non competitive) inhibitors: can bind with a free enzyme and with the enzyme-substrate complex.
4. Non-competitive inhibitors: bind to a free enzyme and an enzyme-substrate complex with the same equilibrium constant.
The science of skin lightening/ depigmentation is growing as each year more compounds are isolated and their mechanism of effect studied. As knowledge of melanocyte biology and underlying processes of melanin synthesis are understood, new approaches to the treatment of skin hyperpigmentation become available. Not only is tyrosinase inhibition of catalytic activity an option, other alternatives include: 1) inhibition of tyrosinase mRNA transcription, 2) aberration of tyrosinase glycosylation and maturation, 3) acceleration of tyrosinase degradation, 4) interference with melanosome maturation and transfer, 5) inhibition of inflammation-induced melanogenic response, and 6) acceleration of skin turnover.
Kojic acid is one of the most commonly used depigmenting agents and a natural agent with few side effects. It is well tolerated by most but skin sensitivity can occur in some individuals and the potential for irritation increase with the concentration. Kojic acid is a fungal metabolite produced by many species of Aspergillus, Acetobacter, and Penicillium. It is know to act as a competitive and reversible inhibitor of tyrosinase which catalyzes the conversion of tyrosine to melanin via 3,4-dihydroxyphenylalanine and dopaquinone. Kojic acid remains the standard against which new de- pigementing agents are measured. As it is a completely natural product its popularity has grown, albeit it is not the most effective.
Arbutin (ß) ( Uva Ursi and bearberry extract, hydroquinone-beta-D-glucopyranoside) is a botanical extract in which the active component hydrolyzes readily into hydroquinone. Researchers shows it inhibits the oxidation of L-DOPA catalysed by mushroom tyrosinase and is effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocyte function. A another study indicated that arbutin inhibits melanin synthesis by inhibition of tyrosinase activity apparently due to the inhibition of melanosomal tyrosinase activity rather than the suppression of this enzyme’s synthesis and expression. Arbutin itself is oxidized at an extremely slow rate, but accelerates when dihydroxyphenylalanine (L-DOPA) becomes available as co factor.
Morus alba, Mulberry extract is a composite of polyphenols which have shown to have 32 fold the inhibitory activity of Kojic acid. It acts non-competitively on both monophenolase and diphenolase activity of mushroom tyrosinase. The inhibtion mechanism of the compound directly inhibits enzyme activity but does not affect gene expression. Aside from its more potent effect than Kojic acid for melanin inhibition, Morus alba extract has also shown superoxide scavenging activity.
Licorice extract, extracts from the roots and seeds of Glycyrrhiza species are commonly used in Asia as a lightening compound. Glabridin and glabrene are the two components of Licorice extract that act in a non competitive manner to inhibit melanogenesis. Glabridine has 15 times the activity of kojic acid and exhibited higher depigmenting activity than arbutin. Glycyrrhizic acid another compound within Morus alba is renowned for it's anti inflammatory and anti oxidant effects.
Raspberry ketone from Rheum officinale, one of the major aromatic compounds of raspberry, is widely used in perfumery, cosmetics, and as a flavoring agent in foodstuffs has shown strong inhibitory effects. Currently it is marketed primarily as a weight loss aid, however it is also known for anti-androgenic activity and anti inflammatory activity. It has also been shown to be an extremely potent tyrosinase inhibitor on par with hydroquinone. The exact mechanism is not completely understood however it is suggested that RK inhibits melanogenesis through a post-transcriptional regulation of tyrosinase gene expression, which results in down regulation of both cellular tyrosinase activity and the amount of tyrosinase protein, while the level of tyrosinase mRNA transcription is not affected. Rk hold particular promise as it is a safe compound and effective on mammalian tyrosinase. RK is also multifunctional as in other research it has shown to reduce the signs of dermal laxity and exhibits some promise in hair loss reduction.
Each compound has quantifiable capacity to affect melanogenesis via specific mechanisms. None are permanent. The complete eradication of pigment from the skin remains dangerous. Melanin is the first line of defense from the ravages of UV damage. When using lightening compounds one must also use a high SPF sunscreen. Sensible precautions must be employed. Endangering one's health for the sake of change of skin color is not worth the long term side effects. When using any homemade creams or lotions, test for sensitivity and observe the reactions. Adjust accordingly or discontinue if necessary.
1. Ando, H.; Kondoh, H.; Ichihashi, M.; Hearing, V.J. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Invest. Dermatol 2007, 127, 751-761.
2. Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003, 16, 101-110.
3. Draelos, Z.D. Skin lightening preparations and the hydroquinone controversy. Dermatol. Ther 2007, 20, 308-313.
4. Halaban, R.; Patton, R.S.; Cheng, E.; Svedine, S.; Trombetta, E.S.; Wahl, M.L.; Ariyan, S.; Hebert, D.N. Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway. J. Biol. Chem 2002, 277, 14821-14828.
5. Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Growth Horm IGF Res. 2008 Aug;18(4):335-44
6. Kim, Y.M.; Yun, J.; Lee, C.K.; Lee, H.; Min, K.R.; Kim, Y. Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J. Biol. Chem 2002, 277, 16340-16344
7. Parvez, S.; Kang, M.; Chung, H.S.; Cho, C.; Hong, M.C.; Shin, M.K.; Bae, H. Survey and mechanism of skin depigmenting and lightening agents. Phytother. Res 2006, 20, 921-934.
8. Rendon, M.I.; Gaviria, J.I. Review of skin-lightening agents. Dermatol. Surg 2005, 31, 886-889.
9. Sang Hee LEE,a Sang Yoon CHOI,a Hocheol KIM,a Jae Sung HWANG,b Byeong Gon LEE,b
Jian Jun GAO,c and Sun Yeou KIM, Mulberroside F Isolated from the Leaves of Morus alba Inhibits Melanin Biosynthesis. Biol. Pharm. Bull. 2002 25(8) 1045—1048
10. Solano, F.; Briganti, S.; Picardo, M.; Ghanem, G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res 2006, 19, 550-571.
11. Victor Chia-Hsiang Lin , Hsiou-Yu Ding , Shiou-Yi Kuo , Ling-Wei Chin , Jiumn-Yih Wu
and Te-Sheng Chang , Evaluation of in Vitro and in Vivo Depigmenting Activity of Raspberry Ketone from Rheum officinale. Int. J. Mol. Sci. 2011, 12, 4819-4835;
12. Wang, N.; Hebert, D.N. Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Res 2006, 19, 3-18.
13. Zhu, W.; Gao, J. The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J. Investig. Dermatol. Symp. Proc 2008, 13, 20-24.
Skin lightening, de pigmentation of the skin is of growing interest
amongst the aging population as well as those choosing to lighten their
skin for cosmetic or cultural reasons. In some countries there remains a
stigma attached if a person is known to be actively lightening their
skin. Skin lightening / whitening may utilize ingredients with various
associated hazards when used inappropriately, while others have a less
toxic effect. Skin lightening, naturally has been explored to varying
degrees of success. Many choose to DIY skin lightening lotions, body
wash, creams, due to the cost as well as the fear of steroids
potentially being included. Lemon juice, lime juice, citric acid and
various other components are used as a simple and moderately effective
methods to lighten the skin. People around the globe of many ethnicity
are looking to lighten skin for personal reasons. Hyper pigmentation due
to UV exposure over a life time has become a common theme. Do It
Yourself methods meet with varying degrees of success. Not all skin
lightening products are created equal, nor do they work along the same
mechanisms. Some are next to useless. To whiten or bleach the skin is
not a simple matter, nor is it permanent. Effective treatment requires
several months before the effects are noticed and are quickly lost due
to sun exposure. Maintaining a consistent regime will play an important
role in the efficacy of any treatment, whether you make it yourself or
purchase from a drugstore.
To beautify the skin, i.e. reduce evidence of age spots, darkened areas of pigmentation, is of great concern to many. An even skin tone is considered by most cultures to be beautiful. How to safely achieve even skin tone for sun damaged skin is more difficult. Skin beauty is a personal journey and the stigma attached to skin lightening is often not considered. The experts on what constitute beautiful skin are the ones in the mirror's reflection. Healthy skin, is generally considered to be even in tone, of smooth texture, unlined and without acne. Many of the natural skin lightening ingredients also contain cross over action in other mechanism due to the complexity of the chemical composition inherent to several of the known plant extract lighteners. While they are effective at skin lightening, they remain effective antioxidants. Whether dark skinned or light skinned, even skin tone remains a desirable aspect of beauty. While many wish to lighten their skin tone, others are trying to go darker. That which constitutes beauty, lies in the eyes of the beholder, even if that remains the self.
As the end user of any lotion, milk , serum, cream, it is the individual experience that determines the efficacy or not thereof. DIY / homemade lotions, bath body wash and serums are made with the goal to lighten the skin, in hopes that pigment will disappear or old age spots likewise. Can this be done safely and without irritation or allergic reactions? Drugstores and big name labels sell lotions that claim to lighten the skin, however the concentrations of the active components are unknown. They may also be in a base that causes allergic reaction, where as the active itself may not. Some actives are inherently unstable, and by the time they reach the consumer, they are of little use. Safest and most effective are not necessarily mutually exclusive when it comes to skin lightening. Safest generally requires longer treatment time.
To improve the efficacy of a skin whitening treatment or regime, it is prudent not to play games with chemicals that are proven to cause permanent damage when it can readily be avoided. Several plant extracts contain effective chemicals for lightening pigmentation and the research has greatly refined the understanding of the mechanisms of action over the years. It remains prudent to keep in mind that not each individual will have the same success,. It would be nice to guarantee the efficacy of a product however far too many variables come into play. The type of oil used to make a homemade/ DIY lotion due to the palmitic acid content can undo the positive effect of the lightening chemical component/ extract. As the consumer knowledge base continues to increase, producers are forced to meet the demand. Unfortunately due to restrictions in various jurisdictions for health and safety concerns, truly effective formulas are not necessarily readily available.
Understanding the pigmentation pathway as currently known is useful prior to examining the various skin-lightening compounds and the assosciated mechanisms of action. Skin color is determined by both the type and quantity of melanin synthesized by the melanocyte and its distribution pattern in the epidermis. The formation of melanin is through a series of oxidative reactions involving the amino acid tyrosine and the enzyme tyrosinase.
Most critical is the first reaction as the reaction sequence that follows proceeds spontaneously at physiological pH. At this point in the sequence, tyrosinase converts tyrosine to dihydroxyphenylalanine (DOPA) and subsequently to dopaquinone. Thereafter, dopaquinone is converted to dopachrome through auto-oxidation, and, finally, to dihydroxyindole or dihydroxyindole-2-carboxylic acid (DHICA) to form eumelanin (black-brown pigment= darken the skin). The latter reaction occurs in the presence of dopachrome tautomerase and DHICA oxidase. In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl DOPA or glutathione DOPA. The latter results in the formation of pheomelanin, a yellow-red pigment. ( influences skin tone )
Tyrosinase regulates melanin synthesis in melanocytic cells. It is a membrane-bound copper containing glycoprotein, and the critical rate-limiting enzyme of melanin production. Tyrosinase is produced only by melanocytic cells, post its synthesis it is further processed in the ER and Golgi. After processing it is transported to melanosomes, where the pigment is synthesized and deposited. Melanosomes are transferred from melanocytes to neighboring keratinocytes and are distributed in the skin and hair to produce visible color. An excess of melanin or abnormal distribution can cause irregular pigementation and hyperpigmentation of the skin. Developing effective therapies to treat disorders of pigementation, disruption of tyrosinase activity is the usual target. Several approaches exist to decreases tyrosinase activity i.e. competitive or non-competitive inhibition of tyrosinase catalytic activity, disruption of tyrosinase maturation or by reduce its stability. Manipulation of tyrosinase levels include modulating of tyrosinase messenger RNA (mRNA) transcription and its post-transcriptional stability or reducing its potential for synthesis at the gene expression level.
Before treating hyperigmentation the etiology must first be elucidated. It is not always clear as there are many factors that influence hyperpigmentation: 1) photo sensitizing agents, 2) hormone imbalance, 3) UV exposure, 4) Systemic disease, 5) drug interactions. etc.
Hydroquinone:
A variety of topical treatments have been developed and some with exceptional effect. The current Gold Standard is the use of Hydroquinone (HQ) . HQ is considered to be one of the most effective in vivo and in vitro inhbitors of melanogensis which causes a reversible inhibition by affecting both DNA and RNA synthesis. The unfortunate aspect is that while it is effective at inhibiting melanocytes it remains cytotoxic to the surrounding cellular structures and leads to degeneration of both collagen and elastin fibers. Inappropriate usage may lead to darkening of the skin. Care must be taken when using potent lightening agents.
Tyrosinase Inhibitors:
There are a variety of effective inhibitors however they are not true inhibitors of tryosinase, rather they act to interfere with the production of melanin. L ascorbic acid is one such molecule. It acts to to reduce o-dopaquinone to dopa, avoiding dopachrome and melanin formation. AA2G is also shown to be particularly effective for those that cannot tolerate the low pH requirement of LAA.
Phenolic compounds are another broad category of which many have been isolated and found to be effective. These enzyme substrates show good affinity for the binding site on tyrosinase and result in a reduction in the formation of dopachrome. Some act as cheltors of copper which also acts to inhibit enzymatic activity via destabilization of tyrosinase.
Acids or bases also act as inactivators of tyrosinase. These act to denature the enzyme, leaving it non functional and as such, inhibit activity.
Suicide substrates are another class of inhibitors and more correctly true inhibitors. These act to bind tyrosinase irreversibly. These inhibitors are catalyzed by tyrosinase forming covalent bonds and inducing the enzyme catalyzing "suicide reaction."
True inhibitors are of four types. 1) competitive inhibitors, 2) noncompetitive inhibitors, 3) mixed (competitive/non-competitive) inhibitors, and 4) non-competitive inhibitors.
1. Competitive inhibitor: a substance that combines with a free enzyme in a manner that prevents substrate binding. That is, the inhibitor and the substrate are mutually exclusive, often because of true competition for the same site.
2. Non competitive inhibitors: can bind only to the enzyme-substrate complex.
3. Mixed (Competitive/ Non competitive) inhibitors: can bind with a free enzyme and with the enzyme-substrate complex.
4. Non-competitive inhibitors: bind to a free enzyme and an enzyme-substrate complex with the same equilibrium constant.
The science of skin lightening/ depigmentation is growing as each year more compounds are isolated and their mechanism of effect studied. As knowledge of melanocyte biology and underlying processes of melanin synthesis are understood, new approaches to the treatment of skin hyperpigmentation become available. Not only is tyrosinase inhibition of catalytic activity an option, other alternatives include: 1) inhibition of tyrosinase mRNA transcription, 2) aberration of tyrosinase glycosylation and maturation, 3) acceleration of tyrosinase degradation, 4) interference with melanosome maturation and transfer, 5) inhibition of inflammation-induced melanogenic response, and 6) acceleration of skin turnover.
Kojic acid is one of the most commonly used depigmenting agents and a natural agent with few side effects. It is well tolerated by most but skin sensitivity can occur in some individuals and the potential for irritation increase with the concentration. Kojic acid is a fungal metabolite produced by many species of Aspergillus, Acetobacter, and Penicillium. It is know to act as a competitive and reversible inhibitor of tyrosinase which catalyzes the conversion of tyrosine to melanin via 3,4-dihydroxyphenylalanine and dopaquinone. Kojic acid remains the standard against which new de- pigementing agents are measured. As it is a completely natural product its popularity has grown, albeit it is not the most effective.
Arbutin (ß) ( Uva Ursi and bearberry extract, hydroquinone-beta-D-glucopyranoside) is a botanical extract in which the active component hydrolyzes readily into hydroquinone. Researchers shows it inhibits the oxidation of L-DOPA catalysed by mushroom tyrosinase and is effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocyte function. A another study indicated that arbutin inhibits melanin synthesis by inhibition of tyrosinase activity apparently due to the inhibition of melanosomal tyrosinase activity rather than the suppression of this enzyme’s synthesis and expression. Arbutin itself is oxidized at an extremely slow rate, but accelerates when dihydroxyphenylalanine (L-DOPA) becomes available as co factor.
Morus alba, Mulberry extract is a composite of polyphenols which have shown to have 32 fold the inhibitory activity of Kojic acid. It acts non-competitively on both monophenolase and diphenolase activity of mushroom tyrosinase. The inhibtion mechanism of the compound directly inhibits enzyme activity but does not affect gene expression. Aside from its more potent effect than Kojic acid for melanin inhibition, Morus alba extract has also shown superoxide scavenging activity.
Licorice extract, extracts from the roots and seeds of Glycyrrhiza species are commonly used in Asia as a lightening compound. Glabridin and glabrene are the two components of Licorice extract that act in a non competitive manner to inhibit melanogenesis. Glabridine has 15 times the activity of kojic acid and exhibited higher depigmenting activity than arbutin. Glycyrrhizic acid another compound within Morus alba is renowned for it's anti inflammatory and anti oxidant effects.
Raspberry ketone from Rheum officinale, one of the major aromatic compounds of raspberry, is widely used in perfumery, cosmetics, and as a flavoring agent in foodstuffs has shown strong inhibitory effects. Currently it is marketed primarily as a weight loss aid, however it is also known for anti-androgenic activity and anti inflammatory activity. It has also been shown to be an extremely potent tyrosinase inhibitor on par with hydroquinone. The exact mechanism is not completely understood however it is suggested that RK inhibits melanogenesis through a post-transcriptional regulation of tyrosinase gene expression, which results in down regulation of both cellular tyrosinase activity and the amount of tyrosinase protein, while the level of tyrosinase mRNA transcription is not affected. Rk hold particular promise as it is a safe compound and effective on mammalian tyrosinase. RK is also multifunctional as in other research it has shown to reduce the signs of dermal laxity and exhibits some promise in hair loss reduction.
Each compound has quantifiable capacity to affect melanogenesis via specific mechanisms. None are permanent. The complete eradication of pigment from the skin remains dangerous. Melanin is the first line of defense from the ravages of UV damage. When using lightening compounds one must also use a high SPF sunscreen. Sensible precautions must be employed. Endangering one's health for the sake of change of skin color is not worth the long term side effects. When using any homemade creams or lotions, test for sensitivity and observe the reactions. Adjust accordingly or discontinue if necessary.
1. Ando, H.; Kondoh, H.; Ichihashi, M.; Hearing, V.J. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Invest. Dermatol 2007, 127, 751-761.
2. Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003, 16, 101-110.
3. Draelos, Z.D. Skin lightening preparations and the hydroquinone controversy. Dermatol. Ther 2007, 20, 308-313.
4. Halaban, R.; Patton, R.S.; Cheng, E.; Svedine, S.; Trombetta, E.S.; Wahl, M.L.; Ariyan, S.; Hebert, D.N. Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway. J. Biol. Chem 2002, 277, 14821-14828.
5. Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Growth Horm IGF Res. 2008 Aug;18(4):335-44
6. Kim, Y.M.; Yun, J.; Lee, C.K.; Lee, H.; Min, K.R.; Kim, Y. Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J. Biol. Chem 2002, 277, 16340-16344
7. Parvez, S.; Kang, M.; Chung, H.S.; Cho, C.; Hong, M.C.; Shin, M.K.; Bae, H. Survey and mechanism of skin depigmenting and lightening agents. Phytother. Res 2006, 20, 921-934.
8. Rendon, M.I.; Gaviria, J.I. Review of skin-lightening agents. Dermatol. Surg 2005, 31, 886-889.
9. Sang Hee LEE,a Sang Yoon CHOI,a Hocheol KIM,a Jae Sung HWANG,b Byeong Gon LEE,b
Jian Jun GAO,c and Sun Yeou KIM, Mulberroside F Isolated from the Leaves of Morus alba Inhibits Melanin Biosynthesis. Biol. Pharm. Bull. 2002 25(8) 1045—1048
10. Solano, F.; Briganti, S.; Picardo, M.; Ghanem, G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res 2006, 19, 550-571.
11. Victor Chia-Hsiang Lin , Hsiou-Yu Ding , Shiou-Yi Kuo , Ling-Wei Chin , Jiumn-Yih Wu
and Te-Sheng Chang , Evaluation of in Vitro and in Vivo Depigmenting Activity of Raspberry Ketone from Rheum officinale. Int. J. Mol. Sci. 2011, 12, 4819-4835;
12. Wang, N.; Hebert, D.N. Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Res 2006, 19, 3-18.
13. Zhu, W.; Gao, J. The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J. Investig. Dermatol. Symp. Proc 2008, 13, 20-24.
