Effect of Guanbaifu(Radix Aconiti Coreani)Before and After Processing on the Metabolomics of Gerbils with Ischemic Stroke
Objective To investigate the effects of raw Guanbaifu(Radix Aconiti Coreani),and its processed products on the urinary metabolites of gerbils with ischemic stroke using non-targeted metabolomics techniques to elucidate the mechanism of anti-stroke effects.Methods Thirty-six gerbils were randomly divided into a control group(CG),a model group(MG),a positive drug group(PG),a raw Guanbaifu(Radix Aconiti Coreani)group(RA),a steamed Guanbaifu(Radix Aconiti Coreani)group(SA)and a Guanbaifu(Radix Aconiti Coreani)processed with ginger and alum group(GA),with six gerbils in each group,except for the CG.After successful modeling,the RA,SA and GA were gavaged with the corresponding herbal whole powder suspension(0.586 mg/g),PG was gavaged with suspension of Naoluotong Granules(脑 络 通 颗 粒,0.390 mg/g)and the CG was gavaged with saline for 14 days.Longa score,triphenyltetrazolium chloride(TTC)staining,and enzyme-linked immunoassay were used to detect the effects of Guanbaifu(Radix Aconiti Coreani)and their processed products on neurological function score,brain tissue infarct volume,oxidative stress level,and inflammatory factor expression,respectively.The urine samples of gerbils in the CG,MG,PG,RA,SA and GA were analyzed by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap-MS);the data were processed by multivariate statistical methods to screen the differential metabolites;the Kyoto Encyclopedia of Genes and Genomes(KEGG)database and MetaboAnalyst 5.0 software were used to analyze the metabolic pathways of the screened differential metabolites.Results Guanbaifu(Radix Aconiti Coreani)and its processed products significantly improved the infarcted area of brain tissue;significantly reduced malondialdehyde(MDA),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)activities in brain tissue and serum(P<0.05),and significantly increased superoxide dismutase(SOD),glutathione(GSH)and nitric oxide(NO)activities(P<0.05).The metabolomic study identified 112 differential metabolites,including L-proline,riboflavin,leukotriene D4,and 7-methylxanthine,as potential biomarkers of ischemic stroke,involving riboflavin metabolism,pyrimidine metabolism,and 14 metabolic pathways such as purine metabolism.The metabolic pathways of the RA were modulated in four of them,including riboflavin metabolism and pyrimidine metabolism;the metabolic pathways of the SA were modulated in five of them,including riboflavin metabolism,pyrimidine metabolism,arginine and proline metabolism;the metabolic pathways of the GA were modulated in two of them,including caffeine metabolism and acetaldehyde and dicarboxylic acid metabolism.Conclusion The results of comparative pharmacodynamic experiments revealed the better effect of steamed Guanbaifu(Radix Aconiti Coreani),and clarified the similarities and differences between raw and processed products on the modulation of potential biomarkers of ischemic stroke.
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