Abstract
Ephedra sinica Stapf (EP) has a long medication history dating back centuries in the world. There were some reports of adverse effects in the central nervous system (CNS) resulting from administration of a drug containing EP or ephedrine. Compared with alkaloid monomer compounds, the effects of EP on the CNS are usually neglected. It is necessary to explore CNS affection which is helpful to use EP rationally. However, the affection and the changes of substances by EP in the brain are still unknown because the effects of drug on the brain also exhibit different tendency and distribution and usually lead to diversity of metabolite alteration in different regions. In this study, metabolomics based on different brain regions was used to investigate the affection mechanism of EP in the CNS. The metabolites in 6 brain regions from a rat that underwent oral administration with EP for 14 days were determined by UPLC/Q-TOF-MS. Brain histological examinations showed that there were no obvious lesions in EP administration groups. Partial least square-discriminant analysis (PLS-DA) displayed that there were significant separations between control and EP administration groups. 7 CNS biomarkers were found and identified in different regions. 3 metabolic pathways were disturbed by EP, including amino acid metabolism, phospholipid metabolism, and amino sugar metabolism. Furthermore, all biomarkers were significantly changed in the cortex after administration. This study may be helpful to understand the affection mechanism of EP in the CNS and improve cognition of brain regional characteristics.
Highlights
Ephedra sinica Stapf (EP) has a long medication history dating back centuries in the world [1]
Six ions with high abundances covering the whole analysis process were selected for method validation. e retention time and mass pairs were as follows: m/z 291.0582, 1.86 min; m/z 162.0939, 3.63 min; m/z 338.3276, 6.31 min; m/z 288.1881, 5.68 min; m/z 476.3287, 8.15 min; m/z 346.3198, 10.35 min. e relative standard deviations (RSDs) of retention time and peak intensities for the selected ion in brain samples were calculated. e repeatability of sample preparation was evaluated through repeated preparation of five identical samples. e precision of injection was tested by six repeated injections in a sample
E RSDs of retention time for stability, precision, and repeatability were to be 0.15–1.04%, 0.20–1.03%, and 0.29–0.98%, while the RSDs of intensity varied within the ranges of 2.46–7.36%, 1.34–5.06%, and 2.17–5.36%. e results indicated that the instrument and methods have good stability, precision, and repeatability, which adapted to analysis of brain metabolites
Summary
Ephedra sinica Stapf (EP) has a long medication history dating back centuries in the world [1]. EP has often been used to treat upper respiratory tract infections (URTIs), headache, general aching, acute glomerulonephritis, and chronic renal failure [2, 3]. Due to its strong pharmacological activity, EP is often adopted as a monarch drug in Chinese medicine formulae, provides the main therapeutic effect, and plays an indispensable role in treating clinical respiratory diseases [5, 6]. Ascribed to clinical symptoms of URTIs, which usually last for 3–10 days, with a few lingering symptoms such as coughing remaining for a longer period [7], patients usually take EP preparations 3–7 days in traditional Chinese therapy or may be extended for weeks in some cases [8, 9]. There were many reports of adverse reactions in the central nervous system (CNS) resulting from longer periods of administration of drug containing EP or ephedrine, and the clinical manifestation varied from dizziness and strokes to seizures [11, 12]
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