Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 128; pp. 149 - 157
• Main Authors: Bian, Qiaoxia, Wang, Weihui, Wang, Nannan, Peng, Yan, Ma, Wen, Dai, Ronghua
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.09.2016
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism; Animals; Arachidonic acid; Arachidonic Acid - metabolism; Benign prostatic hyperplasia; Biomarkers; Biomarkers - metabolism; Chromatography, High Pressure Liquid - methods; Drugs, Chinese Herbal - metabolism; Eicosanoids; Hydroxyeicosatetraenoic Acids - metabolism; Lipoxygenase - metabolism; Male; Medicine, Chinese Traditional - methods; Metabolomics - methods; Plasma - metabolism; Prostaglandin-Endoperoxide Synthases - metabolism; Prostatic Hyperplasia - metabolism; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry - methods; UHPLC–MS/MS; Zishen pill; Eicosanoids; Biomarkers; UHPLC–MS/MS; Benign prostatic hyperplasia; Arachidonic acid; Zishen pill
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2016.05.027

[Display omitted] •Developing the simultaneous determination method of arachidonic acid metabolome in biofluids.•Evaluating the relationship between benign prostatic hyperplasia and AA metabolome.•Study of metabonomics changes after administrated with Zishen pill.•Presenting the interventional effects of drug through COX and LOX pathways of AA metabolism. Zishen pill (ZSP) is a traditional Chinese medicine (TCM) used to treat benign prostatic hyperplasia (BPH). The study used a metabolomic approach based on UHPLC–MS/MS to profile arachidonic acid (AA) metabolic changes and to investigate the interventional mechanisms of ZSP in testosterone- induced BPH rats. In order to explore the potential therapeutic effect of ZSP, rat models were constructed and orally administrated with ZSP. Plasma and urine samples were collected after four weeks and then eleven potential biomarkers (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2α, 8-HETE, PGD2, PGE2 and LTB4) were identified and quantified by UHPLC–MS/MS. The chromatographic separation was carried out with gradient elution using a mobile phase comprised of 0.05% formic acid aqueous solution (pH=3.3) (A) and acetonitrile: methanol (80:20, V/V) (B), and each AA metabolites was measured using electrospray ionization source with negative mode and multiple reaction monitoring. The eleven biomarkers in BPH group rat plasma and urine were significant higher than those in sham group rats. Using the potential biomarkers as a screening index, the results suggest that ZSP can potentially reverse the process of BPH by partially regulating AA metabolism through refrain the expression of cyclooxygenase (COX) and lipoxygenase (LOX). This study demonstrates that a metabolomic strategy is useful for identifying potential BPH biomarkers and investigating the underlying mechanisms of a TCM in BPH treatment.