Objective:

2

To investigate the intervention effect of Dachuanxiong Fang multi-component preparation on acute migraine rats

in order to explore the possible mechanism by using urine metabolomics technology.

Method:

2

The forty SD rats were randomly divided into 5 groups (

n

=8)

control group

model group

low-dose Dachuanxiong Fang multi-component preparation (DCXF) group (0.19 g·kg

-1

)

medium-dose DCXF group (0.37 g·kg

-1

)

and high-dose DCXF group (0.74 g·kg

-1

). Rats were subcutaneously injected with 10 mg·kg

-1

nitroglycerin for modeling

and Dachuanxiong Fang multi-component preparation was administered through intragastric administration. After half an hour of administration

blood was collected from the abdominal aorta

and the content of 5-hydroxytryptamine (5-HT)

5-hydroxyindole-3-acetic acid (5-HIAA)

nitric oxide (NO)

nitric oxide synthase (NOS)

calcitonlin gene related peplide (CGRP)

dopamine(DA) in plasma were determined by enzyme-linked immuno sorbent assay (ELISA) kits. The contents of 5-HT and NOS in the hypothalamus and brainstem of the control group and the model group were analyzed

and the average optical density value was used for statistical analysis. UPLC-TOF/MS combined with principal component analysis (PCA) analysis was used to analyze different groups of rats and discover differential metabolites. Differential metabolites were analyzed by MetaboAnalyst 3.0 software for possible metabolic pathways.

Result:

2

After modeling

compared with the control group

the content of neurotransmitters in the model group was significantly increased (

P

<

0.01). After the intervention with Dachuanxiong Fang multi-component preparation

compared with the model group

the content of neurotransmitters was significantly decreased (

P

<

0.05

P

<

0.01). Based on UPLC-TOF/MS analysis

10 potential biomarkers were found. After the intervention with Dachuanxiong multi-component preparation

the contents of tryptophan and proline were down-regulated

while the contents of gamma-aminobutyric acid(GABA)

lactic acid and

β

-hydroxybutyrate showed an upward trend. According to the metabolic pathway prediction study

metabolic pathways with a higher correlation were found to be alanine

aspartic acid and glutamate metabolism

propionic acid metabolism

nitrogen metabolism and tryptophan metabolism.

Conclusion:

2

The possible metabolism pathway of Dachuanxiong Fang multi-component preparation is mainly amino acid metabolism in urine

and kynurenine is also the product of tryptophan metabolism pathway. The kynurenine metabolic pathway is also one of the main pathways of tryptophan metabolism.