Phytomedicine

Volume 22, Issue 3, 15 March 2015, Pages 406–414

Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer

• Chin-Hsien Tsai^{a, b,} ,
• Sheue-Fen Tzeng^{a, c},
• Shih-Chuan Hsieh^a,
• Chih-Yu Lin^a,
• Chia-Jui Tsai^a,
• Yet-Ran Chen^a,
• Yu-Chih Yang^a,
• Ya-Wen Chou^a,
• Ming-Ting Lee^b,
• Pei-Wen Hsiao^{a, c, ,}

doi:10.1016/j.phymed.2015.01.013

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Abstract

Herbal medicine is a popular complementary or alternative treatment for prostate cancer. Wedelia chinensis has at least three active compounds, wedelolactone, luteolin, and apigenin synergistically inhibiting prostate cancer cell growth in vitro. Here, we report a systematic study to develop a standardized and effect-optimized herbal extract, designated as W. chinensis extract (WCE) to facilitate its future scientific validation and clinical use. Ethanolic extract of dried W. chinensis plant was further condensed, acid hydrolyzed, and enriched with preparative chromatography. The chemical compositions of multiple batches of the standardized preparation WCE were quantified by LC/MS/MS, and biological activities were analyzed by in vitro and in vivo assays. Furthermore, the pharmacokinetics of the holistic WCE were compared with the combination of the equivalent principal active compounds through oral administration. The results indicated that quantitative chemical assay and PSA (prostate-specific antigen)-reporter assay together are suitable to measure the quality and efficacy of a standardized Wedelia extract on a xenograft tumor model. The presence of minor concomitant compounds in WCE prolonged the systemic exposure to the active compounds, thus augmented the anti-tumor efficacy of WCE. In conclusion, a combination of LC/MS/MS and PSA reporter assay is suitable to qualify a standardized preparation of WCE. Furthermore, the pharmacokinetics and oral bioavailability of active compounds demonstrate that holistic WCE exerted additional pharmacological synergy beyond the multi-targeted therapeutic effects caused by more than one active compound. WCE merits a higher priority to be studied for use in prostate cancer treatment.

Keywords

• Prostate cancer;
• Herbal extract;
• Natural products;
• Quality control;
• Pharmacokinetics

Corresponding author at: Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nankang, Taipei 115, Taiwan. Tel.: +886 2 2787 2079; fax: +886 2 2785 9360.

Copyright © 2015 Published by Elsevier GmbH