17. Drug Dev Ind Pharm. 2011 May;37(5):498-505. Epub 2010 Dec 3.  In vitro percutaneous absorption of genistein from topical gels through human skin.  Chadha G, Sathigari S, Parsons DL, Jayachandra Babu R.  Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36830, USA.  

 

The objective of this study was to formulate genistein as a topical gel with various penetration enhancers for increased permeation and retention in human skin. The high performance liquid chromatography assay method was validated for precision and reproducibility. The intra-day and inter-day precision as represented by the coefficient of variation (CV) of the peak areas were <0.44% and <0.67%, respectively. Further, the reproducibility was demonstrated by the CV of the assay at different genistein concentrations, which were <1.64%. Genistein was subjected to various stress conditions to obtain basic information on the appropriate pH and aqueous vehicle for formulating topical gels. Genistein was highly stable under neutral and oxidative conditions, but degraded to highly polar and nonpolar compounds under basic and acidic conditions, respectively. Menthol produced a 9- and 22-fold increase in the flux and skin retention of genistein, respectively, after 24 h of gel application as compared with the control (no enhancer). Cineole showed an approximately 7-fold increase in flux, but skin retention did not increase significantly. Transcutol increased the flux and skin retention of genistein by 5- and 7-fold, respectively. When Transcutol was formulated with Lauroglycol, there was a 13- and 9-fold increase in the flux and skin retention, respectively. Incorporation of penetration enhancers into the topical gel increased the skin permeation of genistein, so that the target delivery rate for its therapeutic effects can be achievable based on the in vitro human skin data generated in this study.  PMID: 21126208  [PubMed - indexed for MEDLINE] 

  

16. J Biol Chem. 2011 Apr 22;286(16):14246-56. Epub 2011 Mar 4.  7,3',4'-Trihydroxyisoflavone, a metabolite of the soy isoflavone daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4.  Lee DE, Lee KW, Byun S, Jung SK, Song N, Lim SH, Heo YS, Kim JE, Kang NJ, Kim BY, Bowden GT, Bode AM, Lee HJ, Dong Z.  World Class University, Biomodulation Major, Department of Agricultural Biotechnology, Seoul 151-921, Republic of Korea. 

 

Nonmelanoma skin cancer is one of the most frequently occurring cancers in the United States. Chronic exposure to UVB irradiation is a major cause of this cancer. Daidzein, along with genistein, is a major isoflavone found in soybeans; however, little is known about the chemopreventive effects of daidzein and its metabolites in UVB-induced skin cancer. Here, we found that 7,3',4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, effectively inhibits UVB-induced cyclooxygenase 2 (COX-2) expression through the inhibition of NF-κB transcription activity in mouse skin epidermal JB6 P+ cells. In contrast, daidzein had no effect on COX-2 expression levels. Data from Western blot and kinase assays showed that 7,3',4'-THIF inhibited Cot and MKK4 activity, thereby suppressing UVB-induced phosphorylation of mitogen-activated protein kinases. Pull-down assays indicated that 7,3',4'-THIF competed with ATP to inhibit Cot or MKK4 activity. Topical application of 7,3',4'-THIF clearly suppressed the incidence and multiplicity of UVB-induced tumors in hairless mouse skin. Hairless mouse skin results also showed that 7,3',4'-THIF inhibits Cot or MKK4 kinase activity directly, resulting in suppressed UVB-induced COX-2 expression. A docking study revealed that 7,3',4'-THIF, but not daidzein, easily docked to the ATP binding site of Cot and MKK4, which is located between the N- and C-lobes of the kinase domain. Collectively, these results provide insight into the biological actions of 7,3',4'-THIF, a potential skin cancer chemopreventive agent.  PMCID: PMC3077626 [Available on 2012/4/22] PMID: 21378167  [PubMed - indexed for MEDLINE]   

 

15. Immunol Cell Biol. 2010 Oct;88(7):727-33. Epub 2010 Mar 9.  Topical isoflavonoids reduce experimental cutaneous inflammation in mice.  Bandara M, Arun SJ, Allanson M, Widyarini S, Chai Z, Reeve VE.  Faculty of Veterinary Science, Photobiology Group, University of Sydney, Sydney, New South Wales, Australia.  

 

The antioxidant and anti-proliferative biological effects of isoflavonoids are relevant properties to counteract the characteristics of many cutaneous diseases. This study uses ultraviolet (UV)B irradiation to induce inflammation in the mouse skin, as a model for some symptoms of cutaneous inflammatory and hyperproliferative diseases such as psoriasis in humans, with the objective of testing two topically applied isoflavonoid compounds for therapeutic properties. UVB exposure resulted in the overexpression of the cytokines, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the adhesion molecule P-cadherin. Infiltration into the dermal compartment of mast cell populations was also induced. These factors are also overexpressed in psoriatic skin. The effect of topical applications of two isoflavonoids, equol and a synthetic analogue NV-38, was tested. Both isoflavonoids dose dependently inhibited the UVB induction of cutaneous TNF-α mRNA and protein, a cytokine critical for the initiation of psoriatic inflammation. Expression of IL-6 mRNA and protein was also decreased, and the number of infiltrating mast cells into the dermis was reduced by both isoflavonoids. Furthermore, the upregulated mRNA and protein levels of P-cadherin, a marker characteristic of cutaneous hyperproliferation, were also normalized by both isoflavonoids. These results suggest that this class of compounds has the potential for useful, innocuous anti-inflammatory therapy from topical application in human cutaneous diseases.  PMID: 20212509  [PubMed - indexed for MEDLINE]   

 

14. Int J Mol Sci. 2010;11(12):4782-95. Epub 2010 Nov 24.  Anti-photoaging effects of soy isoflavone extract (aglycone and acetylglucoside form) from soybean cake.  Huang CC, Hsu BY, Wu NL, Tsui WH, Lin TJ, Su CC, Hung CF.  School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; E-Mail: 054317@mail.fju.edu.tw. 

 

Soy isoflavones, found in soybean and soybean products, have been reported to possess many physiological activities such as antioxidant activity, inhibition of cancer cell proliferation, reduction of cardiovascular risk, prevention of osteoporosis and alleviation of postmenopausal syndrome. In our previous study, soy isoflavone extract ISO-1 (containing 12 soy isoflavones) from soybean cake was demonstrated to prevent skin damage caused by UVB exposure. In this study, soy isoflavone extract from soybean cake was further purified and evaluated for the protective effects on UVB-induced damage. The results revealed that Fraction 3, which contains the aglycone group (daidzein, genistein and glycitein) and acetylglucoside group (acetyldaidzin, acetylgenistin and acetylglycitin) of soy isoflavones, could inhibit UVB-induced death of human keratinocytes and reduce the level of desquamation, transepidermal water loss (TEWL), erythema and epidermal thickness in mouse skin. Furthermore, topical application of Fraction 3 increased the activity of catalase and suppressed cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) expression in mice exposed to UVB. In addition, in comparison with ISO-1 and genistein, the Fraction 3 possessed much greater protective effects on both UVB-induced oxidative stress and keratinocyte death than other fractions. Therefore, the soy isoflavone extract Fraction 3 from soybean cake is a desirable anti-photoaging agent for skin care.  PMCID: PMC3100816 PMID: 21614173  [PubMed]   

 

13. J Ethnopharmacol. 2009 Oct 29;126(1):108-13. Epub 2009 Aug 11.  In vitro and in vivo anti-photoaging effects of an isoflavone extract from soybean cake.  Chiu TM, Huang CC, Lin TJ, Fang JY, Wu NL, Hung CF.  Department of Dermatology, Changhua Christian Hospital, Changhua Hsien, Taiwan, ROC. 

 

ETHNOPHARMACOLOGICAL RELEVANCE: Soy has been used in traditional Chinese medicine for thousands of years for its health and nutritional benefits, as well as to treat and care for the skin. Advanced skin care research has shown that soy isoflavone and genistein are effective in reducing damage to the skin from the sun. AIM OF THE STUDY: To study the protective effects of isoflavone extract from soybean cake against the UVB-induced skin damage. MATERIALS AND METHODS: The in vitro effects and possible mechanisms of soybean extract on UVB protection were determined in HaCaT cells. In the in vivo study, ICR-Foxn/(nu) mice were irradiated with UVB. The epidermal thickness, catalase and the expressions of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) were detected to evaluate the antioxidant and anti-inflammatory activities of the isoflavone extract. RESULTS: Our in vitro studies showed that UVB-induced HaCaT cell death and the phosphorylation of p38, JNK, and ERK1/2 decreased in the presence of isoflavone extract. In the in vivo studies, we found that the topical application of isoflavone extract before UVB irritation decreased the epidermal thickness and the expressions of COX-2 and PCNA and increased catalase concentration. These results showed anti-photoaging effect of isoflavone extract from soybean cake involved the inhibition of UVB-induced apoptosis and inflammation. CONCLUSIONS: It is shown that isoflavone extract from soybean cake may be functional cosmeceutical candidate for skin photoaging.  PMID: 19679176  [PubMed - indexed for MEDLINE] 

  

12. Eur J Obstet Gynecol Reprod Biol. 2009 Oct;146(2):188-92. Epub 2009 May 17.  The effects of topical isoflavones on postmenopausal skin: double-blind and randomized clinical trial of efficacy.  Moraes AB, Haidar MA, Soares Júnior JM, Simões MJ, Baracat EC, Patriarca MT.  Division of Endocrinology Gynecology, Department of Gynecology, UNIFESP, Brazil.  

 

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen and isoflavones on postmenopausal skin morphological parameters. STUDY DESIGN: A randomized, double-blind, estrogen-controlled trial was performed on postmenopausal women treated in the Gynecology Department of the Federal University of São Paulo. This study was designed to analyze the effects of topical administration of estradiol and isoflavones on facial skin for 24 weeks. The participants were divided into two groups: G1-17-betaestradiol 0.01% (n=18) and G2-isoflavones 40% (genistein 4%, n=18). Skin biopsies were performed on each patient before and after the treatment. The skin samples were processed for histological analysis, stained with haematoxylin and eosin, and examined using light microscopy. RESULTS: After 24 weeks of treatment, the estradiol group had a significant increase in skin parameters analyzed compared to the isoflavone group and to the baseline measurements: epidermal thickness (a 75% increase in the estrogen group and 20% in the isoflavone group), number of dermal papillae (a rise of 125% with estrogen, no significant gain with isoflavones), fibroblasts (a 123% accretion with estradiol, no significant gain with isoflavones), and vessels (a 77% increase with estrogen and 36% with isoflavones). CONCLUSION: Our data suggest that estrogens may have a stronger effect on histomorphometrical parameters than isoflavones.  PMID: 19450919  [PubMed - indexed for MEDLINE]   

 

11. Ann N Y Acad Sci. 2009 Aug;1171:415-20.  Anti-inflammatory and anticarcinogenic effect of genistein alone or in combination with capsaicin in TPA-treated rat mammary glands or mammary cancer cell line.  Hwang JT, Lee YK, Shin JI, Park OJ.  Korea Food Research Institute, Seongnam, Gyungki-do, Korea.  

 

The topical application of TPA (12-O-tetradecanoylphorbol-13-acetate) to animal skin or direct treatment of TPA to cell cultures leads to inflammatory responses by enhancing cyclooxygenase 2 (COX-2) expression, and specific COX-2 inhibitors counteract this kind of inflammatory response. Furthermore, suppression of these inflammatory events by dietary-origin chemopreventive agents can provide a potential strategy to control carcinogenesis. In this in vivo study, the mammary glands of mature female rats were treated with TPA, and then the effects of genistein alone or in combination with capsaicin on suppression of inflammatory responses were examined. The combined effects of genistein and capsaicin on COX-2, pJNK, pERK, and pp38 expressions were additive or nonadditive, depending on signals tested. In vitro MCF-7 breast cancer cells, the apoptotic bodies as shown with Hoechst 33342 dye, exhibited a synergistic effect between genistein and capsaicin. The abilities of genistein alone or in combination with capsaicin in inhibiting breast cancer cell proliferation through the modulation of AMPK and COX-2 were tested. AMPK activation by genistein in combination with capsaicin is critical for inhibiting COX-2. We propose that genistein in combination with capsaicin exerts anti-inflammatory and anticarcinogenic properties through the modulation of AMPK and COX-2 and possibly various mitogen-activated protein kinases synergistically or nonsynergistically.  PMID: 19723084  [PubMed - indexed for MEDLINE]   

 

10. Int J Pharm. 2008 Nov 19;364(1):36-44. Epub 2008 Aug 13.  In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein.  Huang ZR, Hung CF, Lin YK, Fang JY.  Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan 333, Taiwan.  

 

Genistein, daidzein, and glycitein are soy isoflavones. These compounds can be used to protect the skin from oxidative stress induced by UVB radiation. To this end, the feasibility of skin absorption of soy isoflavones was evaluated in the present study. As assayed by flow cytometry, UVB-induced H(2)O(2) production in keratinocytes was inhibited by genistein and daidzein, confirming that these two compounds can act as free radical scavengers when keratinocytes are photodamaged. Glycitein showed no protective activity against photodamage. The effects of vehicles on the in vitro topical delivery from saturated solutions such as aqueous buffers and soybean oil were investigated. The isoflavones in a non-ionized form (pH 6) showed higher skin deposition compared to the ionized form (pH 10.8). Soybean oil reduced the isoflavone amount retained in the skin, especially for genistein. Genistein generally exhibited greater skin absorption than did daidzein. However, daidzein permeation was enhanced when an aglycone mixture was used as the active ingredient. An eutectic effect was proposed as the enhancing mechanism. In vivo skin deposition showed a linear correlation with the in vitro results. The safety profiles suggested no or only negligible stratum corneum disruption and skin erythema by topical application of soy isoflavones. It was concluded that topical delivery may serve as a potent route for soy isoflavones against photoaging and photodamage.  PMID: 18761396  [PubMed - indexed for MEDLINE]   

 

9. Photodermatol Photoimmunol Photomed. 2008 Apr;24(2):61-6.  Topical isoflavones provide effective photoprotection to skin.  Lin JY, Tournas JA, Burch JA, Monteiro-Riviere NA, Zielinski J.  Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. lindajylin@adm.cgmh.org.tw  

 

BACKGROUND/PURPOSE: Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone-mediated photoprotection with the pig skin model, a more human-resembling model. METHODS: The pig skin was treated with five well-known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar-simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1-MED intervals. Evaluation was carried out 24 h later by colorimeter-measured erythema and sunburn cell numbers. RESULTS: Topical application of 0.5% solutions of three individual phytoestrogens - genistein, daidzein, biochanin A - are better than similar solutions of equol or formononetin in protecting pig skin from solar-simulated ultraviolet (SSUV)-induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L-ascorbic acid, 1%alpha-tocopherol, and 0.5% ferulic acid. CONCLUSION: Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.  PMID: 18353084  [PubMed - indexed for MEDLINE]  

 

8. Carcinogenesis. 2006 Aug;27(8):1627-35. Epub 2006 Mar 7.  Photoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis.  Moore JO, Wang Y, Stebbins WG, Gao D, Zhou X, Phelps R, Lebwohl M, Wei H.  Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA.  

 

Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase. We previously reported the antiphotocarcinogenic effects of genistein in SKH-1 murine skin, including its capacity for scavenging reactive oxygen species, inhibiting photodynamic DNA damage and downregulating UVB(ultra violet B)-induced signal transduction cascades in carcinogenesis. In this study we elucidate genistein's photoprotective efficacy within the context of full thickness human reconstituted skin relative to acute challenges with ultraviolet-B irradiation. Skin samples were pre-treated with three concentrations of genistein (10, 20 and 50 microM) 1 h prior to UVB radiation at 20 and 60 mJ/cm2. Proliferating cell nuclear antigen (PCNA) and pyrimidine dimer (PD) expression profiles were localized using immunohistochemical analysis on paraffin embedded samples 6 and 12 h post UVB exposure. Genistein dose dependently preserved cutaneous proliferation and repair mechanics at 20 and 60 mJ/cm2, as evidenced by the preservation of proliferating cell populations with increasing genistein concentrations and noticeable paucity in PCNA immunoreactivity in the absence of genistein. Genistein inhibited UV-induced DNA damage, evaluated with PD immunohistochemical expression profiles, demonstrated an inverse relationship with increasing topical genistein concentrations. Irradiation at 20 and 60 mJ/cm2 substantially induced PD formation in the absence of genistein, and a dose dependent inhibition of UVB-induced PD formation was observed relative to increasing genistein concentrations. Collectively all genistein pre-treated samples demonstrated appreciable histologic architectural preservation when compared with untreated specimens. These findings represent a critical link between our animal and cell culture studies with those of human skin and represent the first characterization of the dynamic alterations of UV-induced DNA damage and proliferating cell populations relative to pretreatment with genistein in human reconstituted skin. The implications of our findings serve as compelling validation to our conclusions that genistein may serve as a potent chemopreventive agent against photocarcinogenesis.  PMID: 16522663  [PubMed - indexed for MEDLINE]   

 

7. J Invest Dermatol. 2003 May;120(5):835-41.  Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo.  Kang S, Chung JH, Lee JH, Fisher GJ, Wan YS, Duell EA, Voorhees JJ.  Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA. swkang@umich.edu  

 

Human skin is exposed to solar ultraviolet radiation. Ultraviolet radiation damages human skin and results in an old and wrinkled appearance, called photoaging. We have previously reported that molecular mechanisms by which ultraviolet light causes photoaging involve activation of growth factor and cytokine receptors in keratinocytes and dermal cells. They lead to downstream signal transduction through activation of mitogen-activated protein kinase (extracellular signal-regulated kinase, c-jun N-terminal protein kinase, and p38) pathways. These signaling pathways converge in the nucleus of cells to form an activated complex of transcription factor activator protein 1 (cFos/cJun), which induces matrix metalloproteinases that degrade skin connective tissue. In addition to cell surface receptor activation, generation of reactive oxygen species by ultraviolet radiation is believed to be critical in triggering mitogen-activated protein kinase pathways. We investigated the ability of (i) ultraviolet irradiation to generate reactive oxygen species in human skin in vivo; and (ii) genistein, which possesses both tyrosine kinase inhibitory and antioxidant activities, and n-acetyl cysteine, which can be converted into the endogenous antioxidant glutathione, to impair responses to ultraviolet light that eventuate in photoaging in human skin in vivo. Ultraviolet irradiation caused a rapid and significant increase in hydrogen peroxide levels in human skin in vivo. Pretreatment of human skin with genistein inhibited ultraviolet-induced epidermal growth factor receptor tyrosine kinase activity, whereas n-acetyl cysteine did not. Genistein inhibited ultraviolet induction of both extracellular signal-regulated kinase and cJun N-terminal protein kinase activities. n-Acetyl cysteine inhibited extracellular signal-regulated kinase but not cJun N-terminal protein kinase activation. Both genistein and n-acetyl cysteine prevented ultraviolet induction of cJun protein. Consistent with this, genistein and n-acetyl cysteine blocked ultraviolet induction of cJun-driven enzyme, collagenase. Neither genistein nor n-acetyl cysteine acted as sunscreens as they had no effect on ultraviolet-induced erythema. These data indicate that compounds similar to genistein and n-acetyl cysteine, which possess tyrosine kinase inhibitory and/or antioxidant activities, may prevent photoaging.  PMID: 12713590  [PubMed - indexed for MEDLINE]   

 

6. J Am Acad Dermatol. 2003 Jan;48(1):1-19; quiz 20-2.  Cutaneous photodamage, oxidative stress, and topical antioxidant protection.  Pinnell SR.  Duke University Medical Center, Department of Medicine, Division of Dermatology, Durham, North Carolina 27707, USA. pinne002@mc.duke.edu  Comment in J Am Acad Dermatol. 2003 Dec;49(6):1203-4.  

 

New methods to protect skin from photodamage from sun exposure are necessary if we are to conquer skin cancer and photoaging. Sunscreens are useful, but their protection is not ideal because of inadequate use, incomplete spectral protection, and toxicity. Skin naturally uses antioxidants (AOs) to protect itself from photodamage. This scientific review summarizes what is known about how photodamage occurs; why sunscreens--the current gold standard of photoprotection--are inadequate; and how topical AOs help protect against skin cancer and photoaging changes. This review is intended to be a reference source, including pertinent comprehensive reviews whenever available. Although not all AOs are included, an attempt has been made to select those AOs for which sufficient information is available to document their potential topical uses and benefits. Reviewed are the following physiologic and plant AOs: vitamin C, vitamin E, selenium, zinc, silymarin, soy isoflavones, and tea polyphenols. Their topical use may favorably supplement sunscreen protection and provide additional anticarcinogenic protection. (J Am Acad Dermatol 2003;48:1-19.) Learning objective: At the completion of this learning activity, participants should have an understanding of current information about how the sun damages skin to produce skin cancer and photoaging changes, how the skin naturally protects itself from the sun, the shortcomings of sunscreens, and the added advantages of topical AOs for photoprotection.  PMID: 12522365  [PubMed - indexed for MEDLINE]   

 

5. Skin Pharmacol Appl Skin Physiol. 2002 May-Jun;15(3):175-83. Genistein and daidzein stimulate hyaluronic acid production in transformed human keratinocyte culture and hairless mouse skin. Miyazaki K, Hanamizu T, Iizuka R, Chiba K. Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan. koji-mayazaki@yakult.co.jp

 

We examined the effects of the soy isoflavones genistein (Gen) and daidzein (Dai) on the production of hyaluronic acid (HA) in a transformed human keratinocyte culture and in hairless mouse skin following topical application for 2 weeks. Gen and Dai, but not the glycosides thereof, significantly enhanced the production of HA in vitro and in vivo. Histochemistry using an HA-binding protein revealed that topical Gen and estradiol raised both the density and intensity of HA staining, which was abundant in the murine dermis. It is suggested that Gen and Dai are not released from their respective glycosides in culture or murine skin. Moreover, topical Gen and Dai may prevent and improve the cutaneous alterations caused by the loss of HA in skin. Copyright 2002 S. Karger AG, Basel PMID: 12077470  [PubMed - indexed for MEDLINE]

 

4. Dermatology. 2002;204(4):281-6. Assessment of topical hypopigmenting agents on solar lentigines of Asian women.  Hermanns JF, Petit L, Piérard-Franchimont C, Paquet P, Piérard GE.  Department of Dermatopathology, University Medical Center Sart Tilman and Sauvenière, Liège, Belgium. 

 BACKGROUND: So-called darkened age spots encompass distinct pathological processes. The efficacy of topical depigmenting agents is difficult to objectivate. OBJECTIVE: To assess the hypopigmenting effect of three cosmetic formulations using objective biometrological methods. METHODS: 50 women of South-East Asian ancestry were enrolled in this pilot study. They had solar lentigines according to dermoscopic criteria. The lesions were treated by topical hypopigmenting formulations. Products were applied twice daily for 2 or 3 months. Assessments at 1-month intervals were made using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection and photodensitometry- and image-analysis-assisted corneomelametry. RESULTS: A 20% azelaic acid formulation and another one containing 5% ascorbyl glucosamine, 1% kojic acid and alpha-hydroxyacid esters appeared inefficacious on solar lentigines. A stabilized soy extract showed a better although modest lightening effect when assessed by corneomelametry. The subclinical or faint mottled skin revealed by ultraviolet light examination better responded (p < 0.05) to treatments. CONCLUSION: Focal epidermal hyperpigmentation is better controlled by topical whitening agents when the increase in melanin content reflects a modest functional hyperactivity of melanocytes.  Copyright 2002 S. Karger AG, Basel  PMID: 12077522  [PubMed - indexed for MEDLINE] 

   

3. J Invest Dermatol. 2001 Apr;116(4):587-95.  An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway.  Paine C, Sharlow E, Liebel F, Eisinger M, Shapiro S, Seiberg M.  Johnson & Johnson-Consumer Products Worldwide, Skin Research Center, Skillman, New Jersey 08558, USA. 

 The protease-activated receptor 2, expressed on keratinocytes but not on melanocytes, has been ascribed functional importance in the regulation of pigmentation by phagocytosis of melanosomes. Inhibition of protease-activated receptor 2 activation by synthetic serine protease inhibitors requires keratinocyte-melanocyte contact and results in depigmentation of the dark skinned Yucatan swine, suggesting a new class of depigmenting mechanism and agents. We therefore examined natural agents that could exert their effect via the protease-activated receptor 2 pathway. Here we show that soymilk and the soybean-derived serine protease inhibitors soybean trypsin inhibitor and Bowman-Birk inhibitor inhibit protease-activated receptor 2 cleavage, affect cytoskeletal and cell surface organization, and reduce keratinocyte phagocytosis. The depigmenting activity of these agents and their capability to prevent ultraviolet-induced pigmentation are demonstrated both in vitro and in vivo. These results imply that inhibition of the protease-activated receptor 2 pathway  by soymilk may be used as a natural alternative to skin lightening.  PMID: 11286627  [PubMed - indexed for MEDLINE]

2. Redox Rep. 2000;5(2-3):156-8.  Protective effect of isoflavone derivative against photocarcinogenesis in a mouse model.  Widyarini S, Spinks N, Reeve VE.  Department of Veterinary Anatomy and Pathology, University of Sydney, New South Wales, Australia.  

 

Plant-derived isoflavones are currently receiving much attention because of their phyto-estrogenic and antioxidant activities. In this study, we describe novel photoprotective effects of one isoflavone derivative from red clover (NV07), following its application topically in Skh:HR-1 hairless mice. We found that in mice irradiated in the short-term (3 days) with minimally erythemal solar simulated UV radiation, topical lotions containing NV07 dose-responsively reduced the erythema-associated oedema, the induction of ornithine decarboxylase, and the suppression of contact hypersensitivity. In mice irradiated chronically (50 days), daily application of topical NV07-lotion reduced photocarcinogenesis significantly, and appeared to be actively protective during both the initiation phase and the later promotion phase of tumour induction.  PMID: 10939302  [PubMed - indexed for MEDLINE]       

 

1. Dermatology. 2000;201(2):118-22.  Unraveling the patterns of subclinical pheomelanin-enriched facial hyperpigmentation: effect of depigmenting agents.  Hermanns JF, Petit L, Martalo O, Piérard-Franchimont C, Cauwenbergh G, Piérard GE.  Unit of Dermocosmetology, Department of Dermatopathology, University Medical Center of Liège, Belgium. 

 BACKGROUND: During photoaging, the density of melanin chromatophores is heterogeneous in the epidermis. AIMS: To define the patterns of pheomelanin-enriched melanotic hypermelanosis of  the face in phototype II subjects and to assess the effect of depigmenting agents. Azelaic acid and glycolic acid were tested as well as a soy extract, reported to reduce pigmentation through interaction with the protease-activated receptor 2 (PAR-2) of keratinocytes. METHOD: Evaluations were made by image analysis of high magnification pictures obtained by a video camera equipped with an internal ultraviolet-emitting unit (Visioscan((R))). RESULTS: Three patterns of subclinical facial hypermelanosis were recognized including the spotty perifollicular type, the accretive globular type and the elongated type of the sunny side of wrinkles. Azelaic acid and the soy extract led to significant skin lightening after a 3-week treatment. By contrast, glycolic acid showed an inconsistent effect. CONCLUSION: Sensitive fluorescence video recording combined with image analysis represents an advance in the noninvasive assessment of the mottled subclinical skin pigmentation. The depigmenting effect observed with the soy extract indicates that the inhibition of PAR-2 may be a novel way to approach certain pigmentary disorders of the skin.  Copyright 2000 S. Karger AG, Basel  PMID: 11053913  [PubMed - indexed for MEDLINE] 

Advanced skin care research has shown that soy isoflavone and genistein are effective in reducing damage to the skin from the sun. The ingredient is also known to be an antioxidant and an anti-inflammatory. So isoflavone and genistein are also used for lightening & brightening of the skin.

Soy Isoflavone and Genistein research