title: Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer.
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.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan. Electronic address: tch@gate.sinica.edu.tw.
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sheue-Fen
authors.initials: SF
authors.lastname: Tzeng
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Shih-Chuan
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Tsai
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yet-Ran
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chou
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Ting
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: pwhsiao@gate.sinica.edu.tw.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000592:standards*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008517:Phytotherapy / Q000592:standards*; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000592:standards*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011786:Quality Control; D053719:Tandem Mass Spectrometry; D031209:Wedelia / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Herbal extract; Natural products; Pharmacokinetics; Prostate cancer; Quality control