Abstract
Background We analyzed the effects of total flavonoids from Dracocephalum moldavica L. (D. moldavica L.) on improving chronic mountain sickness (CMS) in rats using the NMR hydrogen spectrum (1H-NMR) metabonomics technology. Method We extracted the total flavonoids of D. moldavica L with 60% ethanol reflux. A CMS model was established with 48 Sprague–Dawley (SD) rats, which were then randomly divided into six groups (n = 8): control group (normal saline, 0.4 mL/100 g/d, ig); model group (normal saline, 0.4 mL/100 g/d, ig); nifedipine group (nifedipine tablets, 2.7 mg/kg/d, ig); and high-, middle-, and low-dose groups of total flavonoids from D. moldavica L. (DML.H, DML.M, and DML.L, receiving total flavonoids from D. moldavica L. at 400, 200, and 100 mg/kg/d, ig, respectively). The sera of the rats in all the groups were determined, and NMR hydrogen spectrum metabolomics was analyzed. The serum contents of apolipoproteins A1 (Apo-A1) and E (Apo-E) were determined, and histopathological changes in the brain tissue of each group were observed. Results Serum tests showed that total flavonoids from D. moldavica L. significantly increased the Apo-A1 and Apo-E levels in rats with CMS (P < 0.05). The results of serum metabonomics showed that total flavonoids from D. moldavica L can alleviate amino acid, energy, and lipid metabolism disorders in rats with CMS. Pathohistological examination of brain tissue showed that these flavonoids improved pathological changes, such as meningeal vasodilation, hyperemia, edema of brain parenchyma, inflammatory cell infiltration, increase in perivascular space, and increase in pyramidal cells. Conclusion Total flavonoids from D. moldavica L. have potential therapeutic effects on CMS. The possible mechanism is the reduction of oxidative damage through the alleviation of metabolism disorder.
Highlights
Chronic mountain sickness (CMS), called Monge’s disease, refers to a kind of comprehensive high-altitude disease that develops in people living in places above 2500 m altitude for a long time
After intervention with different doses of total flavonoids from D. moldavica L., serum metabolites before and after the administration of the flavonoids were analyzed using NMR hydrogen spectrum (1H-NMR) metabonomics. e serum contents of apolipoproteins A1 (Apo-A1) and E (Apo-E) were determined, and histopathological changes in the brain tissue of each group of rats were examined. rough Metabolomics Pathway Analysis (MetPA), we explored the mechanism of the total flavonoids from D. moldavica L. in improving chronic mountain sickness (CMS) in rats from the perspective of systems biology
1H-NMR metabonomics technology was used to analyze differential metabolites in serum, including those involved in glyoxylate and dicarboxylate metabolism; glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism; glycine, serine, and threonine metabolism; synthesis and degradation of ketone bodies; pyruvate metabolism; arginine biosynthesis; butanoate metabolism; tricarboxylic acid cycle (TCA cycle); taurine and hypotaurine metabolism
Summary
Chronic mountain sickness (CMS), called Monge’s disease, refers to a kind of comprehensive high-altitude disease that develops in people living in places above 2500 m altitude for a long time. The most effective way of alleviating CMS is moving an affected individual to a lowaltitude place. This approach is greatly restricted by economic and social factors. (D. moldavica L.) on improving chronic mountain sickness (CMS) in rats using the NMR hydrogen spectrum (1H-NMR) metabonomics technology. Serum tests showed that total flavonoids from D. moldavica L. significantly increased the Apo-A1 and Apo-E levels in rats with CMS (P < 0.05). E results of serum metabonomics showed that total flavonoids from D. moldavica L can alleviate amino acid, energy, and lipid metabolism disorders in rats with CMS. Total flavonoids from D. moldavica L. have potential therapeutic effects on CMS. e possible mechanism is the reduction of oxidative damage through the alleviation of metabolism disorder
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