Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection

Abstract

Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke.

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

“…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]. DHI also exerts a neuroprotective action in a rat model of cerebral I/R injury by preserving the blood-brain barrier, and reversing neutrophil infiltration [87].…”

“…DHI is a composite formula of two eminent Chinese herbal medicine-Salviae Miltiorrhizae (Dan Shen) and Flos Carthami (Hong Hua). Compared with single-target western medicine, DHI is a multi-component and multi-target medicinal preparation, which indicates that DHI may have a wider range of clinical applications [10,86,106].…”

Signature‐oriented investigation of the efficacy of multicomponent drugs against heart failure

“…Dynamic changes of proteins in hiPS-C cells during cardiac dysfunction were investigated by collecting cells after exposure to ET-1 for 12, 24, 48, and 72 h for high-throughput proteomic profiling. An accurate iBAQ-based approach was used (24,31,37), and the iBAQ value of each protein was normalized to the total iBAQ value for all the identified proteins to avoid possible experimental variations (24,31). Three individual samples were analyzed in each group, and dynamic changes were precisely identified by statistical analyses of the measured protein amounts from each individual sample (24).…”

“…Because of the superior comprehensiveness of proteomics and their powerful quantitative ability (27,28), this approach offers an opportunity to identify the changes of the signatures and biomarkers when perturbed with a drug. Next, after a systems-level explanation of the interactions of multiple drug components by a network pharmacology-based (29)(30)(31) approach and final validation in HF rat models, the signature biomarkers regulated by the multicomponent drugs against HF can be confirmed and the corresponding precise clinical localization deduced. The newly developed approach was then applied to a multicomponent conventional drug for cardiac disease, YiXinShu (YXS), a sheng mai san-based TCM formula (32)(33)(34).…”

Pharmacokinetic Study on Protocatechuic Aldehyde and Hydroxysafflor Yellow A of Danhong Injection in Rats with Hyperlipidemia

“…contributed equally to this work. Pharmacology 2018;102:154-160 DOI: 10.1159/000491020 [1,2], is used extensively in the treatment of cardio-cerebrovascular diseases with the functions of promoting blood circulation to remove blood stasis, and dredging the channels. Its various effective ingredients, including protocatechuic aldehyde (PAL) and hydroxysafflor yellow A (HSYA), have been proved to possess a positive effect on anti-thrombotics, regulation of lipid metabolism, atherosclerosis, and anti-oxidants [3][4][5][6].…”