Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Centre of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, Thailand.
Fitoterapia. 2012 Jul;83(5):864-71. doi: 10.1016/j.fitote.2012.03.017. Epub 2012 Mar 21.
Six sesquiterpenes: germacrone (1), zederone (2), dehydrocurdione (3), curcumenol (4), zedoarondiol (5) and isocurcumenol (6) were isolated from rhizomes of Curcuma aeruginosa Roxb. (Zingiberaceae). They inhibited 5α-reductase which converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most potent (IC(50)=0.42±0.05 mg/mL). Compound 1 was anti-androgenic in LNCaP cells when proliferation was testosterone-induced. The growth of flank gland of male Syrian hamsters is dependent on circulating androgen and when maintained with testosterone, 1 (3, 30, 100μg) inhibited growth but was ineffective against DHT. The similar activity profile was observed on the 5α-reductase inhibitor, finasteride (100 μg) treatment group. The androgen receptor binding assay showed that 1 did not bind to the androgen receptor. In conclusion, 1 showed anti-androgenic effect on in vitro and in vivo assays. One of the possible mechanisms was inhibition 5α-reductase activity. Thus, 1 is a potential lead compound for treatment of androgen-dependent disorders.
从莪术(Curcuma aeruginosa Roxb.)根茎中分离得到 6 种倍半萜：倍半萜醇（1）、榄香脂素（2）、脱氢莪术酮（3）、莪术醇（4）、菖蒲酮（5）和异莪术醇（6）。它们抑制 5α-还原酶，将睾酮转化为二氢睾酮（DHT）。倍半萜醇（1）活性最强（IC50=0.42±0.05 mg/mL）。当增殖由睾酮诱导时，化合物 1 在 LNCaP 细胞中具有抗雄激素作用。雄性叙利亚仓鼠侧腺的生长依赖于循环雄激素，当用睾酮维持时，1（3、30、100μg）抑制生长，但对 DHT 无效。在 5α-还原酶抑制剂非那雄胺（100μg）治疗组中观察到相似的活性谱。雄激素受体结合测定表明，1 不与雄激素受体结合。总之，1 在体外和体内试验中均表现出抗雄激素作用。一种可能的机制是抑制 5α-还原酶活性。因此，1 是治疗雄激素依赖性疾病的潜在先导化合物。
