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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

PLS-DA analytical results from urine samples of BCCAO rats treated with Scu (A) or Scue (B) at six therapeutic cycles in positive mode.C, sham-operated group (0–12 h); M, model group (0–12 h); Scu 1–6, after administration of Scu for 0–12 h (Scu1), 12–24 h (Scu2), 24–36 h (Scu3), 36–48 h (Scu4), 48h-60 h (Scu5) and 60–72 h (Scu6); Scue 1–6, after administration of Scue for 0–12 h (Scue1), 12–24 h (Scue2), 24–36 h (Scue3), 36–48 h (Scue4), 48h-60 h (Scue5) and 60–72 h (Scue6). PLS-DA analytical results from BCCAO rat urine samples treated with Scu, Scue, and nimodipine at 12–24 h in positive (C) and negative modes (D). C, sham-operated group; M, model group; Scu, after administration of Scu; Scue, after administration of Scue; N, after administration of nimodipine.
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pone.0131569.g003: PLS-DA analytical results from urine samples of BCCAO rats treated with Scu (A) or Scue (B) at six therapeutic cycles in positive mode.C, sham-operated group (0–12 h); M, model group (0–12 h); Scu 1–6, after administration of Scu for 0–12 h (Scu1), 12–24 h (Scu2), 24–36 h (Scu3), 36–48 h (Scu4), 48h-60 h (Scu5) and 60–72 h (Scu6); Scue 1–6, after administration of Scue for 0–12 h (Scue1), 12–24 h (Scue2), 24–36 h (Scue3), 36–48 h (Scue4), 48h-60 h (Scue5) and 60–72 h (Scue6). PLS-DA analytical results from BCCAO rat urine samples treated with Scu, Scue, and nimodipine at 12–24 h in positive (C) and negative modes (D). C, sham-operated group; M, model group; Scu, after administration of Scu; Scue, after administration of Scue; N, after administration of nimodipine.

Mentions: To understand the metabolic trajectory of the ischemia model and the protective effects of Scu and Scue, the metabolic pattern of the urine samples was plotted using PLS-DA. The R2Y values of the PLS-DA model (Fig 3A and 3B) were 0.871 and 0.84, and Q2 was 0.825 and 0.732, respectively, suggesting that the PLS-DA model had goodness of fit and provided valid predictions. Variations in urine metabolic profiling in Scu- and Scue-treated rats were restored to levels similar to those determined in sham-operated rats after treatment. This finding strongly suggested that Scu and Scue had protective effects. Quantitative evaluation of the relative distances between the treatment and sham-operated groups is rarely reported [30, 34]. In the urine samples, relative distances between the treatment and sham-operated groups in the PLS-DA score plot were quantified. The mean metabolic pattern determined in sham-operated rats was used as a reference for the metabolic patterns in treatment groups [30]. We found that the relative distances in untreated ischemic groups decreased after six cycles, and anesthesia effects did not have statistical difference. The relative distances in the Scu- and Scue-treated groups decreased significantly after six therapeutic cycles when compared to the model group, indicating that Scu and Scue may confer protective effects against cerebral ischemic injury (Table 2).


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)

PLS-DA analytical results from urine samples of BCCAO rats treated with Scu (A) or Scue (B) at six therapeutic cycles in positive mode.C, sham-operated group (0–12 h); M, model group (0–12 h); Scu 1–6, after administration of Scu for 0–12 h (Scu1), 12–24 h (Scu2), 24–36 h (Scu3), 36–48 h (Scu4), 48h-60 h (Scu5) and 60–72 h (Scu6); Scue 1–6, after administration of Scue for 0–12 h (Scue1), 12–24 h (Scue2), 24–36 h (Scue3), 36–48 h (Scue4), 48h-60 h (Scue5) and 60–72 h (Scue6). PLS-DA analytical results from BCCAO rat urine samples treated with Scu, Scue, and nimodipine at 12–24 h in positive (C) and negative modes (D). C, sham-operated group; M, model group; Scu, after administration of Scu; Scue, after administration of Scue; N, after administration of nimodipine.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493097&req=5

pone.0131569.g003: PLS-DA analytical results from urine samples of BCCAO rats treated with Scu (A) or Scue (B) at six therapeutic cycles in positive mode.C, sham-operated group (0–12 h); M, model group (0–12 h); Scu 1–6, after administration of Scu for 0–12 h (Scu1), 12–24 h (Scu2), 24–36 h (Scu3), 36–48 h (Scu4), 48h-60 h (Scu5) and 60–72 h (Scu6); Scue 1–6, after administration of Scue for 0–12 h (Scue1), 12–24 h (Scue2), 24–36 h (Scue3), 36–48 h (Scue4), 48h-60 h (Scue5) and 60–72 h (Scue6). PLS-DA analytical results from BCCAO rat urine samples treated with Scu, Scue, and nimodipine at 12–24 h in positive (C) and negative modes (D). C, sham-operated group; M, model group; Scu, after administration of Scu; Scue, after administration of Scue; N, after administration of nimodipine.
Mentions: To understand the metabolic trajectory of the ischemia model and the protective effects of Scu and Scue, the metabolic pattern of the urine samples was plotted using PLS-DA. The R2Y values of the PLS-DA model (Fig 3A and 3B) were 0.871 and 0.84, and Q2 was 0.825 and 0.732, respectively, suggesting that the PLS-DA model had goodness of fit and provided valid predictions. Variations in urine metabolic profiling in Scu- and Scue-treated rats were restored to levels similar to those determined in sham-operated rats after treatment. This finding strongly suggested that Scu and Scue had protective effects. Quantitative evaluation of the relative distances between the treatment and sham-operated groups is rarely reported [30, 34]. In the urine samples, relative distances between the treatment and sham-operated groups in the PLS-DA score plot were quantified. The mean metabolic pattern determined in sham-operated rats was used as a reference for the metabolic patterns in treatment groups [30]. We found that the relative distances in untreated ischemic groups decreased after six cycles, and anesthesia effects did not have statistical difference. The relative distances in the Scu- and Scue-treated groups decreased significantly after six therapeutic cycles when compared to the model group, indicating that Scu and Scue may confer protective effects against cerebral ischemic injury (Table 2).

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