Dataset Information

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.

ABSTRACT:

Aim

To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI).

Methods

Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods (PCA and PLS-DA) and web-based metabolomics tools (MetPa and MetaboAnalyst) were used to analyze the biological data sets for the amino acids.

Results

Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups.

Conclusion

Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.

SUBMITTER: Guo ZL

PROVIDER: S-EPMC4594181 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.

Guo Zhi-li ZL Zhu Yan Y Su Xiao-tao XT Liu Jun J Yang Qian-xu QX Nan Jing-yi JY Zhao Bu-chang BC Zhang Ying-ying YY Yu Ya-nan YN Li Bing B Xiao Hong-bin HB Wang Zhong Z

Acta pharmacologica Sinica 20150504 6

<h4>Aim</h4>To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI).<h4>Methods</h4>Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum ...[more]

PMID: 25937632

Similar Datasets

Project description:Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

Project description:This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia-reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood-brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia-reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood-brain barrier function, so we chose the blood-brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.

Dataset Information

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.

Aim

Methods

Results

Conclusion

Publications

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets