Advertisement

The extract of Thujae occidentalis semen inhibited 5α-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse

      Abstract

      Background: The conversion of testosterone to dihydrotestosterone; 5α-androstan-17β-ol-3-one by 5α-reductase plays a crucial role in hair baldness and prostatomegaly. Recent approach showed specific inhibitors for 5α-reductase type 2 such as finasteride promoted hair growth in male pattern alopecia. Objective: In order to search for effective medicinal plant extracts applied topically for androgenetic alopecia, we screened natural plant extracts having inhibitory activities of 5α-reductase type 2 and demonstrated its biological function in androgen-related animal models. Methods: We evaluated the inhibition activities of numerous plant extracts by contact cell based metabolic method using a stable HEK 293 cell line expressing human 5α-reductase (type 2). To elucidate the biological activity in vivo, the Thujae occidentalis semen (TOS) extract was topically applied to fuzzy rat and androchronogenetic alopecia (AGA) mouse, respectively. The secreted sebum and the size of sebaceous glands of fuzzy rat were measured after 6 weeks. Also, after the topical treatment with TOS extract and androgen receptor antagonist (cyproterone acetate) simultaneously with subcutaneous injection of testosterone (1 mg/mice/day), hair loss patterns of female B6CBAF1/j hybrid mouse were observed. Results: TOS extract showed higher inhibition activity of 5α-reductase type 2(IC50 value=2.6 μg/ml) than that of γ-linolenic acid, but lower than that of finasteride. When applied to fuzzy rat, the amount of sebum and sebaceous gland size decreased remarkably. In AGA model, alopecia degrees of two groups, treated with TOS extract (P<0.015) or cyproterone acetate (P<0.01), were lower than that of vehicle (propylene glycol:ethanol=7:3) and there was no difference between above two groups. Conclusion: We have demonstrated the inhibitory activity of TOS extract for 5α-reductase type 2 and its biological action in two animal models, suggesting that TOS extract would be used as an effective agent for male pattern baldness by modifying androgen conversion.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Anderson K.M.
        • Liao S.
        Selective retention of dihydrotestosterone by prostatic nuclei.
        Nature. 1968; 219: 277-279
        • Bruchovsky N.
        • Wilson J.D.
        The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro.
        J. Biol. Chem. 1968; 243: 2012-2021
        • Liao S.
        • Kokontis J.
        • Hiipakka R.A.
        Androgen receptors: structures, mutations, antibodies and cellular dynamics.
        J. Steroid Biochem. 1989; 34: 41-51
        • McPhaul M.J.
        • Young M.
        Complexities of androgen action.
        J. Am. Acad. Dermatol. 2001; 45: S87-S94
        • Bruckheimer E.M.
        • Kyprianou N.
        Dihydrotestosterone enhances transforming growth factor-beta-induced apoptosis in hormone-sensitive prostate cancer cells.
        Endocrinology. 2001; 142: 2419-2426
        • Bartsch G.
        • Rittmaster R.S.
        • Klocker H.
        Dihydrotestosterone and the concept of 5-alpha-reductase inhibition in human benign prostatic hyperplasia.
        Eur. Urol. 2000; 37: 367-380
        • Forstrom L.
        The influence of sex hormones on acne.
        Acta Derm. Venereol. 1980; 89: 27-31
        • Faloia E.
        • Filipponi S.
        • Mancini V.
        • Di Marco S.
        • Mantero F.
        Effect of finasteride in idiopathic hirsutism.
        J. Endocrinol. Invest. 1998; 21: 694-698
        • Liao S.
        • Hiipakka R.A.
        Selective inhibition of steroid 5-alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate.
        Biochem. Biophys. Res. Commun. 1995; 214: 833-838
        • Shimizu K.
        • Fukuda M.
        • Kondo R.
        • Sakai K.
        The 5-alpha-reductase inhibitory components from heartwood of Artocarpus incisus: structure–activity investigations.
        Planta Medica. 2000; 66: 16-19
        • Ishiguro K.
        • Oku H.
        • Kato T.
        Testosterone 5-alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina.
        Phytother. Res. 2000; 14: 544-546
        • Liang T.
        • Liao S.
        Inhibition of steroid 5-alpha-reductase by specific aliphatic unsaturated fatty acids.
        Biochem. J. 1992; 285: 557-562
        • Reichert W.
        • Hartmann R.W.
        • Jose J.
        Stable expression of the human 5-alpha-reductase isoenzymes type I and type II in HEK293 cells to identify dual and selective inhibitors.
        J. Enzyme Inhib. 2001; 16: 47-53
        • Kim D.K.
        The textbook of pharmacognosy. Dongmyong, Seoul2002
        • Ye F.
        • Imamura K.
        • Imanishi N.
        • Rhodes L.
        • Uno H.
        Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.
        Skin Pharmacol. 1997; 10: 288-297
        • Matias J.R.
        • Malloy V.
        • Orentreich N.
        Animal models of androgen-dependent disorders of the pilosebaceous apparatus. 1. The androchronogenetic alopecia (AGA) mouse as a model for male-pattern baldness.
        Arch. Dermatol. Res. 1989; 281: 247-253
        • Sundberg J.P.
        • King L.E.
        • Bascom C.
        Animal models for male pattern (androgenetic) alopecia.
        Eur. J. Dermatol. 2001; 11: 321-325
        • Andersson S.
        • Russell D.W.
        Structural and biochemical properties of cloned and expressed human and rat steroid 5-alpha-reductases.
        Proc. Natl. Acad. Sci. USA. 1990; 87: 3640-3644
        • Gerst C.
        • Dalko M.
        • et al.
        Type-1 steroid 5α-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5a-reductase.
        Exp. Dermatol. 2002; 11: 52-58
        • Matias J.R.
        • Orentreich N.
        The effect of testosterone, cyproterone acetate, and minoxidil on hair loss in the androchronogenetic alopecia mouse.
        Clin. Dermatol. 1988; 6: 169-176
        • Reichert W.
        • Michel A.
        • Hartmann R.W.
        • Jose J.
        Stable expression of human 5alpha-reductase type II in COS1 cells due to chromosomal gene integration: a novel tool for inhibitor identification.
        J. Steroid Biochem. Mol. Biol. 2001; 78: 275-284
        • Bayram F.
        • Muderris I.I.
        • Guven M.
        • Kelestimur F.
        Comparison of high-dose finasteride (5 mg/day) versus low-dose finasteride (2.5 mg/day) in the treatment of hirsutism.
        Eur. J. Endocrinol. 2001; 147: 467-471
        • Jenkins E.P.
        • Hsich C.-L.
        • Milatovitch A.
        Chracterization and chromosomal mapping of a human steroid 5α-reductase gene and pseudogene and mapping of the mouse homologue.
        Genomics. 1991; 11: 1102-1112