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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

Changes in the relative quantities of target metabolites identified in different groups.Um, urine metabolites; Bm, brain metabolites; and Pm, plasma metabolites. Statistical analysis compared with the sham-operated group, △p <0.05, △△p<0.01, and compared with the model group, *p<0.05, **p<0.01; (A) 9 endogenous metabolites in the urine; (B) 8 endogenous metabolites in the brain tissue; and (C) 6 endogenous metabolites in the plasma.
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pone.0131569.g004: Changes in the relative quantities of target metabolites identified in different groups.Um, urine metabolites; Bm, brain metabolites; and Pm, plasma metabolites. Statistical analysis compared with the sham-operated group, △p <0.05, △△p<0.01, and compared with the model group, *p<0.05, **p<0.01; (A) 9 endogenous metabolites in the urine; (B) 8 endogenous metabolites in the brain tissue; and (C) 6 endogenous metabolites in the plasma.

Mentions: Additionally, changes in the relative quantities of the endogenous metabolites identified in different groups were analyzed to characterize the protective effects of Scu and Scue (Fig 4). The quantities of these key biomarkers were more similar to those of the Sham-operated group when compared to the model group. Furthermore, the relative quantities of these biomarkers were altered after pretreatment with Scu and Scue, according to a parametric t-test. This result indicated that Scu and Scue might regulate endogenous metabolite levels.


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)

Changes in the relative quantities of target metabolites identified in different groups.Um, urine metabolites; Bm, brain metabolites; and Pm, plasma metabolites. Statistical analysis compared with the sham-operated group, △p <0.05, △△p<0.01, and compared with the model group, *p<0.05, **p<0.01; (A) 9 endogenous metabolites in the urine; (B) 8 endogenous metabolites in the brain tissue; and (C) 6 endogenous metabolites in the plasma.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131569.g004: Changes in the relative quantities of target metabolites identified in different groups.Um, urine metabolites; Bm, brain metabolites; and Pm, plasma metabolites. Statistical analysis compared with the sham-operated group, △p <0.05, △△p<0.01, and compared with the model group, *p<0.05, **p<0.01; (A) 9 endogenous metabolites in the urine; (B) 8 endogenous metabolites in the brain tissue; and (C) 6 endogenous metabolites in the plasma.
Mentions: Additionally, changes in the relative quantities of the endogenous metabolites identified in different groups were analyzed to characterize the protective effects of Scu and Scue (Fig 4). The quantities of these key biomarkers were more similar to those of the Sham-operated group when compared to the model group. Furthermore, the relative quantities of these biomarkers were altered after pretreatment with Scu and Scue, according to a parametric t-test. This result indicated that Scu and Scue might regulate endogenous metabolite levels.

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