Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb.

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 5 alpha-reductase which converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most potent (IC50 = 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, 100 mu g) inhibited growth but was ineffective against DHT. The similar activity profile was observed on the 5a-reductase inhibitor, finasteride (100 mu g) 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 5a-reductase activity. Thus, 1 is a potential lead compound for treatment of androgen-dependent disorders. (C) 2012 Elsevier B.V. All rights reserved.