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J Pharm Biomed Anal. 2018 Oct 25;160:1-11. doi: 10.1016/j.jpba.2018.07.042. Epub 2018 Jul 21.

Cross-platform metabolic profiling deciphering the potential targets of Shenfu injection against acute viral myocarditis in mice.

Author information

1
Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
2
Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
3
Student Brigade, College of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China.
4
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
5
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: lwting84@163.com.
6
Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. Electronic address: wuhongfmmu@163.com.

Abstract

Acute viral myocarditis (AVMC) is typically caused by cardiotropic viral infection. There is a paucity of specific treatment options available with proven efficacy. Chinese patented pharmaceutical product Shenfu injection (SFI) has potent efficacy on treating AVMC in clinical practice. However, the molecular mechanism is still unknown. We employed cross-platform metabolomics combined with computational systems analysis, based on reversed-phase liquid chromatography-mass spectrometry (RPLC-MS), hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) and gas chromatography-mass spectrometry (GC-MS), to deciphering the targeted metabolic pathways of SFI against AVMC induced by coxsackievirus B3 (CVB3). Quantitative real-time PCR (qRT-PCR) technique was further applied to determining the expressions of the key genes associated with the SFI-targeted metabolic pathways. We have identified 48 significantly changed metabolites related to CVB3-induced AVMC, and SFI can significantly regulate the abnormalities of 33 metabolites and 9 relevant enzymes. Combined metabolic pathway enrichment and topology analyses revealed that the mechanisms of SFI against CVB3-induced AVMC may be attributed to modulating the disordered homeostasis of sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and TCA cycle. It provides new experimental information on the pathogenesis of AVMC, unravels the potential targeted metabolic pathways of SFI against AVMC on the whole metabolic network and highlights the importance of metabolomics combined with computational systems analysis as a potential tool for deciphering drug-targeted metabolic pathways.

KEYWORDS:

Acute viral myocarditis; Drug targets; GC–MS; LC–MS; Metabolomics; Shenfu injection

PMID:
30053682
DOI:
10.1016/j.jpba.2018.07.042
[Indexed for MEDLINE]

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