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Inhibition of Rat 5α-Reductase Activity and Testosterone-Induced Sebum Synthesis in Hamster Sebocytes by an Extract of Quercus acutissima Cortex.

Koseki J, Matsumoto T, Matsubara Y, Tsuchiya K, Mizuhara Y, Sekiguchi K, Nishimura H, Watanabe J, Kaneko A, Hattori T, Maemura K, Kase Y - Evid Based Complement Alternat Med (2015)

Bottom Line: Results.Conclusions.BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.

View Article: PubMed Central - PubMed

Affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.

ABSTRACT
Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (-)-epicatechin gallate, and (-)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.

No MeSH data available.


Related in: MedlinePlus

Representative TLC-image showing inhibition of rat liver microsomal 5α-reductase in testosterone metabolism by BK treatment. Testosterone (T.) was incubated at a final concentration of 3.5 μmol/L for 30 min in the presence or absence of rat liver microsomes (40 μg/mL) and the cofactors. Bokusoku (BK) was added at 30 μg/mL before starting the reaction. The androgens were extracted with ethyl acetate after the incubation and analyzed by TLC. All androgen standards were applied at 0.1 μg/μL/spot. DHT: dihydrotestosterone, A. diol: 5α-androstane-3α,17β-diol.
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fig1: Representative TLC-image showing inhibition of rat liver microsomal 5α-reductase in testosterone metabolism by BK treatment. Testosterone (T.) was incubated at a final concentration of 3.5 μmol/L for 30 min in the presence or absence of rat liver microsomes (40 μg/mL) and the cofactors. Bokusoku (BK) was added at 30 μg/mL before starting the reaction. The androgens were extracted with ethyl acetate after the incubation and analyzed by TLC. All androgen standards were applied at 0.1 μg/μL/spot. DHT: dihydrotestosterone, A. diol: 5α-androstane-3α,17β-diol.

Mentions: We first evaluated the effects of BK in a 5α-reductase assay using rat liver microsomes. In this assay, testosterone added to the enzymatic reaction as a substrate was metabolized to DHT by 5α-reductase, followed by the subsequent conversion to 5α-androstane-3,17-diol by aldo-keto reductase. As shown in Figure 1, a representative TLC image, exogenous testosterone was dramatically decreased in the control. In addition, 5α-androstane-3,17-diol was found at a position of Rf 0.243, while the androgen standards testosterone, 5α-androstane-3,17-diol, and DHT appeared at Rf 0.224, 0.243, and 0.342, respectively. In contrast, the spot of testosterone treated with 30 μg/mL BK was not changed compared with that of testosterone alone without microsomes, showing that BK strongly inhibited the metabolism of testosterone.


Inhibition of Rat 5α-Reductase Activity and Testosterone-Induced Sebum Synthesis in Hamster Sebocytes by an Extract of Quercus acutissima Cortex.

Koseki J, Matsumoto T, Matsubara Y, Tsuchiya K, Mizuhara Y, Sekiguchi K, Nishimura H, Watanabe J, Kaneko A, Hattori T, Maemura K, Kase Y - Evid Based Complement Alternat Med (2015)

Representative TLC-image showing inhibition of rat liver microsomal 5α-reductase in testosterone metabolism by BK treatment. Testosterone (T.) was incubated at a final concentration of 3.5 μmol/L for 30 min in the presence or absence of rat liver microsomes (40 μg/mL) and the cofactors. Bokusoku (BK) was added at 30 μg/mL before starting the reaction. The androgens were extracted with ethyl acetate after the incubation and analyzed by TLC. All androgen standards were applied at 0.1 μg/μL/spot. DHT: dihydrotestosterone, A. diol: 5α-androstane-3α,17β-diol.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4325551&req=5

fig1: Representative TLC-image showing inhibition of rat liver microsomal 5α-reductase in testosterone metabolism by BK treatment. Testosterone (T.) was incubated at a final concentration of 3.5 μmol/L for 30 min in the presence or absence of rat liver microsomes (40 μg/mL) and the cofactors. Bokusoku (BK) was added at 30 μg/mL before starting the reaction. The androgens were extracted with ethyl acetate after the incubation and analyzed by TLC. All androgen standards were applied at 0.1 μg/μL/spot. DHT: dihydrotestosterone, A. diol: 5α-androstane-3α,17β-diol.
Mentions: We first evaluated the effects of BK in a 5α-reductase assay using rat liver microsomes. In this assay, testosterone added to the enzymatic reaction as a substrate was metabolized to DHT by 5α-reductase, followed by the subsequent conversion to 5α-androstane-3,17-diol by aldo-keto reductase. As shown in Figure 1, a representative TLC image, exogenous testosterone was dramatically decreased in the control. In addition, 5α-androstane-3,17-diol was found at a position of Rf 0.243, while the androgen standards testosterone, 5α-androstane-3,17-diol, and DHT appeared at Rf 0.224, 0.243, and 0.342, respectively. In contrast, the spot of testosterone treated with 30 μg/mL BK was not changed compared with that of testosterone alone without microsomes, showing that BK strongly inhibited the metabolism of testosterone.

Bottom Line: Results.Conclusions.BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.

View Article: PubMed Central - PubMed

Affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.

ABSTRACT
Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (-)-epicatechin gallate, and (-)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.

No MeSH data available.


Related in: MedlinePlus