Skin Care Research: Soy Isoflavone and Genistein for DIY Skin Care Recipes

"Genistein has been demonstrated to inhibit photocarcinogenesis and photoaging in mice, as well as photodamage (particularly UVB-induced skin burns) in humans, via potent antioxidant action, the protection of oxidative and photodamaged DNA, and downregulation of UVB-induced signal transduction cascades (J. Nutr. 2003;133[11 suppl. 1]:3811S-19S).

Perhaps not surprisingly, then, genistein, along with N-acetylcysteine, has also been found to inhibit the expression of tropoelastin—a main component of elastic fibers—when used to pretreat skin subsequently exposed for 24 hours to heat treatment (J. Invest. Dermatol. 2005;124:70–8).

In a study focusing on the generation of reactive oxygen species and the capacity of genistein (and N-acetylcysteine) to inhibit UV effects that lead to in vivo photoaging in humans, pretreatment with the isoflavone impaired UV-induced epidermal growth factor receptor tyrosine kinase activity, as well as UV-induced activities of extracellular signal-regulated kinase and cJun N-terminal protein kinase.

Genistein also inhibited UV induction of cJun protein, cJun-driven enzyme, and collagenase (J. Invest. Dermatol. 2003;120:835–41).

The researchers concluded that these results support the notion that genistein's antioxidant activities are consistent with the prevention of photoaging.

Furthermore, genistein has been found to enhance melanin production. That ability, combined with the compound's known capacity to spur tyrosinase activity, has led some authors to conclude that genistein shields melanocytes from UVB-induced melanoma in whites (Adv. Exp. Med. Biol. 2004;546:121–65).
Equol, a gastrointestinal metabolite of genistein, was recently found to significantly protect the skin of hairless mice against carcinogenesis resulting from chronic exposure to solar-simulated UV, topical treatments with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), or a combination of the two.

Equol lotion was applied daily, and tumor development was monitored for 40 weeks. The results revealed significant delays in tumor appearance and lower tumor number in the groups treated with the genistein derivative. Furthermore, in the groups treated with solar-simulated UV alone or combined with the carcinogen, the proportion of tumors progressing from benign papillomas to malignant squamous cell carcinomas was significantly reduced, as was the average diameter of the carcinomas (Photochem. Photobiol. 2005;81:32–7).
And in a short-term experiment, the authors noted that equol inhibited, in a dose-dependent manner, the simulated solar UV induction of ornithine decarboxylase—a tumor-promotion biomarker enzyme—in the skin.

In an earlier experiment using genistein and its metabolites, UVB-induced hydrogen peroxide production, contact hypersensitivity, and inflammatory edema in hairless mice were mitigated by topically applied equol, isoequol, and dehydroequol, with equol as the most effective (Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2003;147:137–45; Photochem. Photobiol. 2001;74:465–70).

In two experiments performed in the same laboratory, investigators found that topical genistein confers skin protection from psoralen plus ultraviolet A-induced (PUVA-induced) photodamage. Specifically, SKH-1 female mice were administered genistein in a dimethyl sulfoxide/acetone solution 1 hour post 8-methoxypsoralen dosing and 1 hour before UVA exposure. PUVA-induced skin thickening, erythema, and ulceration were significantly diminished in a dose-dependent fashion (Carcinogenesis 2002;23:317–21).

Recently, the pretreatment of mice with genistein 1 hour before UVB exposure was shown to significantly suppress hydrogen peroxide and malondialdehyde in skin as well as 8-hydroxy-2-deoxyguanosine in the epidermis and internal organs. The authors concluded that genistein can directly scavenge reactive oxygen species spawned by UVB, or indirectly reverse the photoinduced oxidative trends through its anti-inflammatory activity, thus displaying distinct antiphotocarcinogenic characteristics (Cancer Lett. 2002;185:21–9).

In one of the more pivotal animal studies of the chemopreventive effects of the soy isoflavone performed by the same team, investigators showed in a two-stage mouse carcinogenesis model that genistein significantly inhibited skin tumorigenesis initiated by DMBA and promoted by 12-O-tetradecanoylphorbol-13-acetate. In the female SENCAR mice studied, topically applied genistein lowered tumor incidence by 20% and multiplicity by 50% (Carcinogenesis 1998;19:1509–14).

Genistein also consistently and significantly inhibited tissue-plasminogen activator-promoted (TPA-promoted) skin tumorigenesis in two additional promotion studies performed by the same lab on CD-1 and SENCAR mice. In these experiments, tumor multiplicity was markedly reduced, whereas tumor incidence was reduced to a lesser extent." BAUMANN LS, Skin & Allergy News- 2005 11 (Vol. 36, Issue 11)

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.

"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." Read more

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." Read more

Isoflavone genistein: photoprotection and clinical implications in dermatology.

Wei H, Saladi R, Lu Y, Wang Y, Palep SR, Moore J, Phelps R, Shyong E, Lebwohl MG., Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA.

"Genistein is a soybean isoflavone with diverse biological activities. It is a potent antioxidant, a specific inhibitor of protein tyrosine kinase, and a phytoestrogen. In recent years, increasing evidence has accumulated that this natural ingredient shows preventative and therapeutic effects for breast and prostate cancers, postmenopausal syndrome, osteoporosis, and cardiovascular diseases in animals and humans. In the past decade we have conducted a series of studies and demonstrated that genistein has significant antiphotocarcinogenic and antiphotoaging effects. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice, and photodamage in humans. The mechanisms of action involve protection of oxidative and photodynamically damaged DNA, downregulation of UVB-activated signal transduction cascades, and antioxidant activities. In this article, we review the biological activities of genistein, as well as published and unpublished research from our laboratory. In addition, we discuss the potential application of genistein to clinical dermatology." Read more

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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, a anti-inflammatory, for lightening & brightening of the skin and to stimulate HA production.

Soy Isoflavone and Genistein research

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