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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.


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The chemical structures of scutellarin and scutellarein.
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pone.0131569.g001: The chemical structures of scutellarin and scutellarein.

Mentions: Scutellarin (Scu) (Fig 1) is the main active compound in breviscapine, which is extracted from the Chinese herb Erigeron breviscapus (vant.) Hand. Mazz. This herb has been used clinically to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases such as hypertension, cerebral thrombosis, and cerebral hemorrhage in China since 1984 [6]. Modern pharmacological studies have demonstrated that Scu treatment induces neuroprotective effects, by acting as a vasodilator, antioxidant, and anti-inflammatory agent. Scu also plays a role in anti-excitotoxicity and the blockage of calcium (Ca2+) channels [7–12]. Within the intestine, Scu is more readily absorbed in its hydrolyzed form, scutellarein (Scue) (Fig 1). One study reported that Scue was more easily absorbed after oral administration than Scu, when administered in equal doses. Previous studies have also demonstrated that Scu and Scue could prevent neuronal injury and Scue have better protective effects than Scu in a rat cerebral ischemia model [13]. However, the precise mechanisms mediating the neuroprotective role of Scu and Scue remain unknown.


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)

The chemical structures of scutellarin and scutellarein.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131569.g001: The chemical structures of scutellarin and scutellarein.
Mentions: Scutellarin (Scu) (Fig 1) is the main active compound in breviscapine, which is extracted from the Chinese herb Erigeron breviscapus (vant.) Hand. Mazz. This herb has been used clinically to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases such as hypertension, cerebral thrombosis, and cerebral hemorrhage in China since 1984 [6]. Modern pharmacological studies have demonstrated that Scu treatment induces neuroprotective effects, by acting as a vasodilator, antioxidant, and anti-inflammatory agent. Scu also plays a role in anti-excitotoxicity and the blockage of calcium (Ca2+) channels [7–12]. Within the intestine, Scu is more readily absorbed in its hydrolyzed form, scutellarein (Scue) (Fig 1). One study reported that Scue was more easily absorbed after oral administration than Scu, when administered in equal doses. Previous studies have also demonstrated that Scu and Scue could prevent neuronal injury and Scue have better protective effects than Scu in a rat cerebral ischemia model [13]. However, the precise mechanisms mediating the neuroprotective role of Scu and Scue remain unknown.

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