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Comparative Metabolomic Analysis of the Neuroprotective Effects of Scutellarin and Scutellarein against Ischemic Insult.

Tang H, Tang Y, Li NG, Lin H, Li W, Shi Q, Zhang W, Zhang P, Dong Z, Shen M, Gu T, Duan JA - PLoS ONE (2015)

Bottom Line: Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu.We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu.These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.

ABSTRACT
For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

No MeSH data available.


Related in: MedlinePlus

Metabolomics pathway analysis (MetPA) summary.(A) Urine, a) sphingolipid metabolism and b) lysine biosynthesis; (B) hippocampal tissue, a) alanine, aspartate, and glutamate metabolism; and (C) Plasma, a) sphingolipid metabolism.
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pone.0131569.g005: Metabolomics pathway analysis (MetPA) summary.(A) Urine, a) sphingolipid metabolism and b) lysine biosynthesis; (B) hippocampal tissue, a) alanine, aspartate, and glutamate metabolism; and (C) Plasma, a) sphingolipid metabolism.

Mentions: To determine possible pathways contributing to ischemia-reperfusion injury, a metabolomics pathway analysis (MetPA) was performed to identify metabolic pathways and their networks using an online database. This analysis resulted in the construction of 11 metabolic pathways in urine, 14 metabolic pathways in hippocampual tissue, and 3 metabolic pathways in the plasma (Fig 5) that were important for host-responses to ischemic injury. Among the metabolic pathways identified, sphingolipid metabolism (impact-value: 0.16) and lysine biosynthesis (impact-value: 0.11) in urine; alanine, aspartate, and glutamate metabolism (impact-value: 0.26) in hippocampal tissue; and sphingolipid metabolism (impact-value: 0.29) in plasma were determined to be the most important.


Comparative Metabolomic Analysis of the Neuroprotective Effects of Scutellarin and Scutellarein against Ischemic Insult.

Tang H, Tang Y, Li NG, Lin H, Li W, Shi Q, Zhang W, Zhang P, Dong Z, Shen M, Gu T, Duan JA - PLoS ONE (2015)

Metabolomics pathway analysis (MetPA) summary.(A) Urine, a) sphingolipid metabolism and b) lysine biosynthesis; (B) hippocampal tissue, a) alanine, aspartate, and glutamate metabolism; and (C) Plasma, a) sphingolipid metabolism.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493097&req=5

pone.0131569.g005: Metabolomics pathway analysis (MetPA) summary.(A) Urine, a) sphingolipid metabolism and b) lysine biosynthesis; (B) hippocampal tissue, a) alanine, aspartate, and glutamate metabolism; and (C) Plasma, a) sphingolipid metabolism.
Mentions: To determine possible pathways contributing to ischemia-reperfusion injury, a metabolomics pathway analysis (MetPA) was performed to identify metabolic pathways and their networks using an online database. This analysis resulted in the construction of 11 metabolic pathways in urine, 14 metabolic pathways in hippocampual tissue, and 3 metabolic pathways in the plasma (Fig 5) that were important for host-responses to ischemic injury. Among the metabolic pathways identified, sphingolipid metabolism (impact-value: 0.16) and lysine biosynthesis (impact-value: 0.11) in urine; alanine, aspartate, and glutamate metabolism (impact-value: 0.26) in hippocampal tissue; and sphingolipid metabolism (impact-value: 0.29) in plasma were determined to be the most important.

Bottom Line: Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu.We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu.These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.

ABSTRACT
For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

No MeSH data available.


Related in: MedlinePlus