title: Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Centre of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, Thailand.
authors.forename: Nungruthai
authors.initials: N
authors.lastname: Suphrom
authors.forename: Ganniga
authors.initials: G
authors.lastname: Pumthong
authors.forename: Nantaka
authors.initials: N
authors.lastname: Khorana
authors.forename: Neti
authors.initials: N
authors.lastname: Waranuch
authors.forename: Nanteetip
authors.initials: N
authors.lastname: Limpeanchob
authors.forename: Kornkanok
authors.initials: K
authors.lastname: Ingkaninan
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D030024:Curcuma / Q000737:chemistry*; D018120:Finasteride / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D027343:Rhizome; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D045788:Sesquiterpenes, Germacrane / Q000302:isolation & purification / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D010936:Plant Extracts; D011944:Receptors, Androgen; D012717:Sesquiterpenes; D045788:Sesquiterpenes, Germacrane; D013739:Testosterone; D018120:Finasteride; C048393:germacrone