Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine.
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.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Qiaoxia
Q
Bian
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Weihui
W
Wang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Nannan
N
Wang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Yan
Y
Peng
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wen
W
Ma
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: ronghuadai@sina.com.
Ronghua
R
Dai
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D055432:Metabolomics / Q000379:methods; D010949:Plasma / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C047628:8-hydroxyeicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases
Arachidonic acid; Benign prostatic hyperplasia; Biomarkers; Eicosanoids; UHPLC–MS/MS; Zishen pill