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Title: Dynamics of progestogenic activity in serum following administration of Ligusticum chuanxiong
Authors: Lim, L.S.
Shen, P. 
Gong, Y.H. 
Yong, E.L. 
Lee, L.S.
Keywords: Ligusticum chuanxiong
Progestogenic activity
Issue Date: 2006
Source: Lim, L.S., Shen, P., Gong, Y.H., Yong, E.L., Lee, L.S. (2006). Dynamics of progestogenic activity in serum following administration of Ligusticum chuanxiong. Life Sciences 79 (13) : 1274-1280. ScholarBank@NUS Repository.
Abstract: Many women are using botanical alternatives for menopausal hormone replacement therapy (HRT) because current progestins, compounds with progesterone activity, have adverse risk profiles. However the development of phyto-progestins for HRT is hampered by the absence of basic pharmacokinetic/pharmacodynamic (PK/PD) data due to the lack of methods to capture summated effects of the numerous compounds that contribute to bioactivity in vivo. In this study, we explored the utility of progesterone receptor (PR)-driven bioassays to track changes in serum progestogenic activity following administration of traditional Chinese medicinal herb, Ligusticum chuanxiong, with potent progestogenic activity. Sensitive and specific (> 300-fold) increases in progestogenic activity were observed when HeLa cells transfected with PR and a PR-driven promoter were exposed to the progestogenic drug, medroxy-progesterone acetate (MPA), suggesting the utility of the bioassay to measure progestogenic effects for PK/PD studies. Progestogens were administered to male Sprague-Dawley rats and serum extracted for measurement of progestogenic activity. Effect-time studies indicate that injection of MPA and L. chuanxiong extract raised area-under-curve of progestogenic activity in sera by 8.2-fold (p < 0.001) and 4.5-fold (p < 0.01) respectively, compared to sera from rats administered vehicle only. Administration of MPA and L. chuanxiong extract by the oral route resulted in a 5.4 (p < 0.001) and 2.3-fold (p = 0.07) increase respectively. Our data suggest that PR-responsive reporter gene bioassays can measure bioavailability of compounds, known and unknown, of complex botanicals for hormone replacement therapy. L. chuanxiong extracts exert progestogenic activity in vivo, and may have utility for progesterone-replacement therapy. © 2006 Elsevier Inc. All rights reserved.
Source Title: Life Sciences
ISSN: 00243205
DOI: 10.1016/j.lfs.2006.03.039
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