Arachidonic acid metabonomics study for understanding therapeutic mechanism of Huo Luo Xiao Ling Dan on rat model of rheumatoid arthritis

Nannan Wang; Xiaoning Zhao; Jiaxin Huai; Yiran Li; Congcong Cheng; Kaishun Bi; Ronghua Dai

doi:10.1016/j.jep.2018.02.027

Arachidonic acid metabonomics study for understanding therapeutic mechanism of Huo Luo Xiao Ling Dan on rat model of rheumatoid arthritis

J Ethnopharmacol. 2018 May 10:217:205-211. doi: 10.1016/j.jep.2018.02.027. Epub 2018 Feb 21.

Authors

Nannan Wang¹, Xiaoning Zhao², Jiaxin Huai³, Yiran Li⁴, Congcong Cheng⁵, Kaishun Bi⁶, Ronghua Dai⁷

Affiliations

¹ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: wnn19881016@sina.com.
² School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: zhaoxn1992@sina.com.
³ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: 18304026245@163.com.
⁴ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: 15134148769@163.com.
⁵ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: chengcongcong333@sina.com.
⁶ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: kaishunbi.syphu@gmail.com.
⁷ School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: ronghuadai@sina.com.

PMID: 29474901
DOI: 10.1016/j.jep.2018.02.027

Abstract

Ethnopharmacological relevance: Huo Luo Xiao Ling Dan (HLXLD), a traditional Chinese medicine (TCM), is commonly used for the treatment of rheumatoid arthritis (RA).

Aim of the study: To explore the potential therapeutic mechanism of HLXLD on anti-inflammatory activity.

Materials and methods: A metabolomic approach based on UFLC-MS/MS to profile arachidonic acid (AA) metabolic changes was used. The cyclooxygenase (COX) and lipoxygenase (LOX) catalyzed metabolites in plasma were quantified on 7, 14, 21, and 28 days after the rats injected with Complete Freund's adjuvant and orally administrated with HLXLD, methotrexate and dexamethasone in parallel as the positive control drugs.

Results: Nineteen metabolites involved in COX and LOX pathways in RA model group were significant increased compared with normal group (P < 0.05), including 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, 8-HETE, leukotriene B₄(LTB₄), prostaglandin E₂ (PGE₂), PGI₂, PGD₂, PGF_2α, thromboxane B₂ (TXB₂), etc. From day 7 to day 28, the trajectory direction of HLXLD group and positive control groups gradually moved towards the initial space, and the concentrations of AA and its metabolites after HLXLD treatment were significantly reduced in dual pathways compared to control groups.

Conclusion: HLXLD induced a substantial change in the AA metabolic profiles through refrain the expression of COX and LOX. The present investigation also highlights that distinct ingredients of this formula tend to inhibit different target to achieve a therapeutic effect.

Keywords: 12-HETE, (PubChem CID:5283154); 13-HODE, (PubChem CID:6443013); 13-oxoODE, (PubChem CID:6446027); 15-HETE, (PubChem CID:5280724); 5-HETE, (PubChem CID:5353349); 8-HETE, (PubChem CID:5283154); 9-HODE, (PubChem CID:5282945); 9-oxoODE, (PubChem CID:9839084); AA, (PubChem CID:444899); Arachidonic acid; Huo Luo Xiao Ling Dan; LTB4, (PubChem CID:5280492); LTC4, (PubChem CID:5280493); LTE4, (PubChem CID:5280879); Metabonomics; PGD2, (PubChem CID:448457); PGE2 (PubChem CID:5280360); PGF2α, (PubChem CID:5280363); PGI2, (PubChem CID:5282411); Rheumatoid arthritis; TXA2, (PubChem CID:5280497); TXB2, (PubChem CID:5283137); UFLC-MS/MS.

MeSH terms

Animals
Antirheumatic Agents / pharmacology*
Arachidonic Acid / blood*
Arthritis, Experimental / blood
Arthritis, Experimental / chemically induced
Arthritis, Experimental / drug therapy*
Biomarkers / blood
Chromatography, Liquid
Dexamethasone / pharmacology
Discriminant Analysis
Drugs, Chinese Herbal / pharmacology*
Freund's Adjuvant
Least-Squares Analysis
Lipoxygenase / metabolism
Male
Metabolomics / methods*
Methotrexate / pharmacology
Prostaglandin-Endoperoxide Synthases / metabolism
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Time Factors

Substances

Antirheumatic Agents
Biomarkers
Drugs, Chinese Herbal
huo luo xiao ling dan
Arachidonic Acid
Dexamethasone
Freund's Adjuvant
Lipoxygenase
Prostaglandin-Endoperoxide Synthases
Methotrexate