Structure–activity relationships for inhibition of human 5α-reductases by polyphenols

Hiipakka, Richard A.; Zhang, Hanzhong; Dai, Wei; Dai, Qing; Liao, Shutsung

doi:10.1016/s0006-2952(02)00848-1

Cited by 193 publications

(178 citation statements)

References 54 publications

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“…As the only structural difference between EGCG and EC is the presence of a gallate group at the 3' position in EGCG, we expect that this group is critical for the potent ability of EGCG to inhibit testosterone production. This structure-activity relationship has been observed by other authors [28][29][30]. As the inhibition was observed with EGCG, but not with EC, the effect cannot be attributed to the antioxidant properties characteristic of both of these catechins.…”

Section: Discussionsupporting

confidence: 86%

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Figueiroa¹,

Vieira²,

Leite³

et al. 2009

Asian J Androl

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This study investigated the acute effects of green tea extract (GTE) and its polyphenol constituents, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin (EC), on basal and stimulated testosterone production by rat Leydig cells in vitro. Leydig cells purified in a Percoll gradient were incubated for 3 h with GTE, EGCG or EC and the testosterone precursor androstenedione, in the presence or absence of either protein kinase A (PKA) or protein kinase C (PKC) activators. The reversibility of the effect was studied by pretreating cells for 15 min with GTE or EGCG, allowing them to recover for 1 h and challenging them for 2 h with human chorionic gonadotropin (hCG), luteinizing hormone releasing hormone (LHRH), 22(R)-hydroxycholesterol or androstenedione. GTE and EGCG, but not EC, inhibited both basal and kinase-stimulated testosterone production. Under the pretreatment conditions, the inhibitory effect of the higher concentration of GTE/EGCG on hCG/LHRH-stimulated or 22(R)-hydroxycholesterol-induced testosterone production was maintained, whereas androstenedione-supported testosterone production returned to control levels. At the lower concentration of GTE/EGCG, the inhibitory effect of these polyphenols on 22(R)-hydroxycholesterol-supported testosterone production was reversed. The inhibitory effects of GTE may be explained by the action of its principal component, EGCG, and the presence of a gallate group in its structure seems important for its high efficacy in inhibiting testosterone production. The mechanisms underlying the effects of GTE and EGCG involve the inhibition of the PKA/PKC signalling pathways, as well as the inhibition of P450 side-chain cleavage enzyme and 17b-hydroxysteroid dehydrogenase function.

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Section: Discussionsupporting

confidence: 86%

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Figueiroa¹,

Vieira²,

Leite³

et al. 2009

Asian J Androl

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“…Many reports proved the structure-activity relationships (Cutter et al, 2001;Nihal et al, 2000;Hiipakka et al, 2002) of EGCG in the biological system. It is known that the structure of EGCG would quickly change in some conditions and that the structural rearrangement would easily occur in vivo.…”

Section: Introductionmentioning

confidence: 97%

Cytotoxicity of epigallocatechin-3-gallate to LNCaP cells in the presence of Cu2+

Shen

Xiong³

2005

J Zheijang Univ Sci B

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Epigallocatechin-3-gallate (EGCG) has shown remarkably anti-cancer activity, with its bioactivity being related to reactive conditions, such as pH and metal ions. The present study investigated the degradation of EGCG and its effect on prostate cancer cell in the presence of Cu 2+. EGCG was incubated with prostate cancer cells, LNCaP, pretreated with or without Cu 2+ . EGCG in F-12 medium was quantified using HPLC and the viability of cells was assessed by gel electrophoresis, flow cytometry, and electron microscope. The results of HPLC showed that EGCG degraded completely within 12 h in F-12 medium with or without Cu 2+. Gel electrophoresis and flow cytometry did not detect apoptosis of LNCaP cells when they were incubated with EGCG. Electron microscopy examination revealed that EGCG-Cu 2+ complex led to damage of cytoplasm membrane in LNCaP cells. It was speculated that not EGCG, but its oxide and complex with Cu 2+ , are the bioactive components responsible for its cytotoxicity to LNCaP prostate cancer cells.

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“…Furthermore, soy isoflavones are considered to have beneficial effects on the skin via mechanisms such as prevention of lipid oxidation of the skin tissue ( 8 ), stimulation of fibroblast proliferation ( 9 ), reduction of collagen degradation ( 10 ), and inhibition of 5 ␣ -reductase ( 11 ), and have been widely used as ingredients of cosmetics ( 12 ). Moreover, cosmetics containing isoflavones are reported to retard skin aging ( 13 ).…”

mentioning

confidence: 99%

Oral Intake of Soy Isoflavone Aglycone Improves the Aged Skin of Adult Women

Izumi

Saito

Obata

et al. 2007

J Nutr Sci Vitaminol

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Summary A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of soy isoflavone aglycone on the aged skin of middle-aged women. Twenty-six women volunteers in their late 30s and early 40s were randomly assigned to receive either a test food (13 women, the test food group) or a placebo food (13 women, the control group). These groups were given the test food (40 mg of soy isoflavone aglycone per day) and placebo, respectively, for 12 wk. The extent of linear and fine wrinkles at the lateral angle of the eyes was selected as the major evaluation criterion to assess the effects of foods, and the wrinkles' area ratio was used as the evaluation parameter. The extent of skin microrelief at the lateral angle of eyes and that of malar skin elasticity were used as secondary evaluation criteria, and the skin microrelief 's area ratio and recovery of skin elasticity were used as the respective evaluation parameters. These parameters were assessed 4, 8, and 12 wk after the start of the test food or placebo intake. The test food group showed a statistically significant improvement of fine wrinkles at week 12 ( p Ͻ 0.05) and of malar skin elasticity at week 8 ( p Ͻ 0.05), compared with the control group. Although there was no significant difference between the test food group and the control group regarding effects on skin microrelief at lateral angle of the eyes, a significant intragroup improvement was observed at week 8 in the test food group ( p Ͻ 0.05). As for the test food safety, none of the subjects presented adverse symptoms during the study period or discontinued the intake of the test food. These data indicate that the oral intake of 40 mg soy isoflavone aglycones per day improves the aged skin of middle-aged women. Key Words isoflavone, aglycone, skin, wrinkle, elasticity Soy isoflavone has been reported to have an estrogenlike effect ( 1 , 2 ). Such an effect suggests that soy isoflavones may contribute to prevent disorders such as osteoporosis ( 3 ), atherosclerosis ( 4 ), and menopausal syndrome ( 5 ) that are associated with a reduced secretion of estrogens in postmenopausal women. Numerous epidemiological studies on the mortality of hormonedependent cancers such as breast cancer ( 6 ) and prostate cancer ( 7 ) have found a negative correlation between intake of soybean, especially soy isoflavones, and the incidence of these cancers.Furthermore, soy isoflavones are considered to have beneficial effects on the skin via mechanisms such as prevention of lipid oxidation of the skin tissue ( 8 ), stimulation of fibroblast proliferation ( 9 ), reduction of collagen degradation ( 10 ), and inhibition of 5 ␣ -reductase ( 11 ), and have been widely used as ingredients of cosmetics ( 12 ). Moreover, cosmetics containing isoflavones are reported to retard skin aging ( 13 ). Soy isoflavones are chemically comprised of aglycone and glycosides, and all the beneficial effects on the human skin mentioned above have been confirmed to derive from aglycone ( 12 , 14 , 15 ). An isoflavone intake...

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Structure–activity relationships for inhibition of human 5α-reductases by polyphenols

Cited by 193 publications

References 54 publications

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Green tea polyphenols inhibit testosterone production in rat Leydig cells

Cytotoxicity of epigallocatechin-3-gallate to LNCaP cells in the presence of Cu2+

Oral Intake of Soy Isoflavone Aglycone Improves the Aged Skin of Adult Women

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