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.

Danhong Promotes Angiogenesis in Diabetic Mice after Critical Limb Ischemia by Activation of CSE-H2S-VEGF Axis

“…Exploring the effects of TCM on improvement of vascular microenvironment and functional recovery has significant clinical implications. Based on results from the present study, DH not only improved angiogenesis but also promoted ischemic organs' function recovery [ 29 , 30 ], while our data are consistent with clinical experience and encourage clinical studies in the vast spectrum of diabetic patients. Association between local CSE-H 2 S-VEGF system and DH protective effects opens up the possibility that DH might act similar to H 2 S-donor drugs, which warrants further research.…”

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

“…Administration of DHI inhibits cerebral infarction in rats subjected to cerebral ischemia and improves neurological deficits. This protection may be achieved through the regulation of amino acid metabolites and metabolic pathways [84,85]. A study of transcription factors in cerebral ischemic injury showed that eight transcription factors, such as cyclic AMP-dependent transcription factor 1 (ATF1) and pre-B cell leukemia transcription factor 1 (PBX1) are target transcription factors responsible for DHI-mediated protection against cerebral ischemic injury [86].…”

Danhong Injection Protects Hemorrhagic Brain by Increasing Peroxiredoxin 1 in Aged Rats

“…A commonly used dosage of DHI in ischemic stroke of a previous study was converted (Guo et al, 2015), and the clinical practice dose (1.0 ml/kg. d) was chosen for the present study.…”

“…DHI has been considered to accelerate blood circulation and remove blood stasis (Zhang et al, 2016). Hence, this has been widely used in Chinese clinical practice for treating cardiovascular and cerebral occlusive diseases (Chen et al, 2011), such as myocardial and cerebral ischemia injury, but is prohibited for ICH treatment according to its instruction for use (Guan et al, 2013;Guo et al, 2015). Its remarkable neuroprotective effects are mainly attributed to the antioxidative and anti-inflammatory function of DHI (Sun et al, 2009;Lyu et al, 2017).…”