Objective: To investigate the metabonomic characteristics of arachidonic acid(AA) in the prostate of benign prostatic hyperplasia (BPH) rats after the intervention of the flavonoids extract of Anemarrhenae Rhizoma. Methods: Shim-PACK XR-ODS C18(75 mm×3.0 mm, 2.2 μm) column was performed in UPLC assay. The mobile phase A was 0.05% formic acid aqueous solution(concentrated ammonia test solution adjusted to pH 3.3)and mobile phase B was methanol-acetonitrile (20∶80, v/v). Gradient elution was performed at the flow rate of 0.3 mL·min-1, the column temperature was 40 ℃, and the injection volume was 10 μL. Negative ionscanning and multiple reaction monitoring(MRM) mode was employed formass spectrometry.The prostate tissues of rats in the sham group, BPH model group, flavonoids group and positive control group were collected and detected, and a total of eleven substances[including arachidonic acid (AA), 5-hydroxyeicosatetraenoic acid (5-HETE), 8-hydroxyeicosatetraenoic acid (8-HETE), 11-hydroxyeicosatetraenoic acid (11-HETE), 12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyeicosatetraenoic acid (15-HETE), leukotriene B4 (LTB4), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), prostaglandin H2 (PGH2), thromboxane B2 (TXB2)]were quantitatively analyzed by ultra-fast liquid chromatography tandem mass spectrometry(UFLC-MS/MS). Results: The objects to be measured could be well detected and its calibration curves were good linear in the linear range. The extraction recovery rates of 11 components to be tested in tissue samples at high, medium, and low concentrations were all greater than 75.7%, with matrix effects ranging from 85.5% to 106.3%, accuracy RSD<11.2%, and intra day and inter day precision RSD<11.0% and 9.5%, respectively.The selectivity, accuracy and precision, recovery, matrix effects, and stability of the method met the requirements. Studies had shown that the concentrations of AA and its metabolites in BPH model group rat prostate were significant higher than those in sham group rats.The flavonoids extract of Anemarrhenae Rhizoma could change the development process of BPH and effectively down-regulate the concentrations of AA and its metabolites in the BPH rat prostate.Conclusion: The flavonoids extract of Anemarrhenae Rhizoma can regulate AA metabolism through two pathway of lipoxygenase(LOX) and cyclooxygenase(COX), thereby inhibiting the inflammatory process occurring in BPH.
CAO Xiao-tong, JIANG Shu-qin, KONG Wei-gui, SHANG Ying, LIAO Jun, JU Tao, DAI Rong-hua
. Effect of flavonoids extract of Anemarrhenae Rhizoma on the metabolism of arachidonic acid in benign prostatic hyperplasia rats based on targeted metabonomics*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(7)
: 1195
-1204
.
DOI: 10.16155/j.0254-1793.2023.07.13
[1] LIM KB. Epidemiology of clinical benign prostatic hyperplasia[J].Asian J Urol, 2017, 4(3):148
[2] MCCLUREA T, RICKEB J. What is new in prostate artery embolization for lower urinary tract symptoms?[J].Eur Urol Focus, 2018, 4(1):31
[3] VELAGALA SR, SEIFER P, DANSRANJAVIN T, et al. Epigenetical analyses on inflammatory factors in patients with prostatitis, BPH and prostate cancer: discovering the link between inflammation and carcinogenesis[J].Eur Urol Suppl, 2014, 13(1):568
[4] DONNELL RF. Benign prostate hyperplasia: a review of the year′s progress from bench to clinic[J].Curr Opin Urol, 2011, 21(1):22
[5] LLOYD GL, MARKS JM, RICKE WA. Benign prostatic hyperplasia and lower urinary tract symptoms: what is the role and significance of inflammation?[J].Curr Urol Rep, 2019, 20(9):54
[6] BIAN QX, WANG WH, WANG NN, et al. Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine[J].J Pharm Biomed Anal, 2016, 128: 149
[7] YAGAMI T, YAMAMOTO Y, KOMA H. Physiological and pathological roles of 15-deoxy-delta12,14-prostaglandin J2 in the central nervous system and neurological diseases[J].Mol Neurobiol, 2018, 55(3):2227
[8] KROETZ DL, ZELDIN DC. Cytochrome P450 pathways of arachidonic acid metabolism[J].Curr Opin Lipidol, 2002, 13(3):273
[9] ALTAVILLA D, MINUTOLI L, POLITO F, et al. Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia[J].Br J Pharmacol, 2012, 167(1):95
[10] SAHA S, SADHUKHAN P, SIL C. Mangiferin: axanthonoid with multipotent anti-inflammatory potential[J].Biofactors, 2016, 42(5):459
[11] BHATIA HS, CANDELARIO-JALIL E, DE OLIVEIRA AC, et al. Mangiferin inhibits cyclooxygenase-2 expression and prostaglandin E2 production in activated rat microglial cells[J].Arch Biochem Biophys, 2008, 477(2):253
[12] ZHANG QJ, YUE L. Inhibitory activity of mangiferin on helicobacter pylori-induced inflammation in human gastric carcinoma AGS cells[J].Afr J Tradit Complement Altern Med, 2016, 14(1):263
[13] WANG HT, LI J, MA ST, et al. A study on the prevention and treatment of murine calvarial inflammatory osteolysis induced by ultra-high-molecular-weight polyethylene particles with neomangiferin[J].Exp Ther Med, 2018, 16(5):3889
[14] 袁欣, 韩莉花, 张娜, 等. 异芒果苷对高脂饮食诱导大鼠肝脏损伤的改善作用[J].南京中医药大学学报, 2019, 35(4):453
YUAN X, HANG LH, ZHANG N, et al. Isomangiferin attenuates high fat diet induced liver injury in rats[J].J Nanjing Univ Tradit Chin Med, 2019, 35(4):453
[15] KARNOVSKY A, LI S. Pathway analysis for targeted and untargeted metabolomics[J].Methods Mol Biol, 2020, 2104: 387
[16] 闻永举,能力强,申秀丽.知母总黄酮提取工艺的研究[J].时珍国医国药, 2008, 19(10):2497
WEN YJ, NENG LQ, SHEN XL. Study on extraction technology of total flavonoids of Anemarrhena[J].Lishizhen Med Mater Med Res, 2008, 19(10):2497
[17] ZHAO XN, ZHANG T, LI YR, et al. Compatibility effects of herb pair Phellodendri Chinensis Cortex and Anemarrhenae Rhizomaon benign prostatic hyperplasia using targeted metabolomics[J].Biomed Chromatogr, 2018, 32(10):e4296
[18] WANG R, KOBAYASHI Y, LIN Y, et al. A phytosterol enriched refined extract of Brassica campestris L. pollen significantly improves benign prostatic hyperplasia (BPH) in a rat model as compared to the classical TCM pollen preparation Qianlie Kang Pule'antablets[J].Phytomedicine, 2015, 22(1):145
[19] MONK JM, TURK HF, FAN Y, et al. Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and Th1 cell-mediated inflammation and colitis severity[J].MediatorsInflamm, 2014, 2014: 1
[20] TUNCTAN B, SENOL SP, TEMIZ RM, et al. Eicosanoids derived from cytochrome P450 pathway of arachidonic acid and inflammatory shock[J].Prostaglandins Other Lipid Mediat, 2019, 145: 106377
[21] CALDER PC. Omega-3 fatty acids and inflammatory processes[J].Nutrients, 2010, 2(3):355
