Dimeric progestins from rhizomes of Ligusticum chuanxiong.
Five dimeric phthalides were isolated from rhizomes of Ligusticum chuanxiong and their structures deduced based on spectral data. All compounds and their parent extracts were assessed for progesterone-like activity using a progesterone receptor driven reporter-gene bioassay. Among all the compounds, riligustilide, displayed weak progesterone-like activity (EC50 approximately 81 microM), whereas, (3Z')-(3a'R,6'R,3R,6R,7R)-3,8-dihydro-6.6',7.3a'-diligustilide (Mr: 382, EC50 approximately 90 nM), was found to be a potent and specific activator of the progesterone receptor. Levistolide A, although having a very similar plenary structure, was inactive indicating the importance of stereochemistry of chiral centers and flexibility of butylidene side chain for progestogenic activity. These bioactive phthalides and their parent extracts (EC50 approximately 8 microg/ml) may have utility for treatment of conditions requiring progesterone action.
Lim
L S
LS
Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University Hospital, 119074, Republic of Singapore.
Shen
P
P
Gong
Y H
YH
Yong
E L
EL
D001681:Biological Assay; D019281:Dimerization; D004365:Drugs, Chinese Herbal; D017930:Genes, Reporter; D030004:Ligusticum / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D011372:Progestins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry*; D013237:Stereoisomerism
D004365:Drugs, Chinese Herbal; D010796:Phthalic Anhydrides; D010936:Plant Extracts; D011372:Progestins; D011980:Receptors, Progesterone; C026105:butylidenephthalide