Work

Investigation of the Mechanism of Action of the Mongolian Medicine Eerdun Wurile Basic Formula in the Treatment of Ischemic Stroke Through Transcriptomics and Metabolomics Integration

Year: 2025

Type: article

Abstract: Objective The Eerdun Wurile Basic Formula (EWB) of Mongolian medicine has been widely used for the prevention and treatment of ischemic stroke, but its mechanism of action remains unclear. In this study, we combined transcriptomics, metabolomics, and in vivo experiments to explore the therapeutic mechanism of EWB in ischemic stroke, providing a scientific basis for clinical treatment. Methods SD rats were divided into six groups: Sham operation group, MCAO/R group, MCAO/R + Nimodipine group, MCAO/R + EWB low-dose group (EWB-L group), MCAO/R + EWB medium-dose group (EWB-M group), and MCAO/R + EWB high-dose group (EWB-H group). The efficacy was evaluated using the Zea-Longa five-point neurological deficit score, rat survival rate, open field test, and Morris water maze test, along with hematoxylin and eosin (H&E) and TUNEL staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Transcriptomics and metabolomics analyses were conducted to identify key genes and metabolites, and qRT-PCR and western blot (WB) were used to verify key targets and elucidate the mechanism. Results Compared with the sham operation group, the model group exhibited significant neurological deficits in rats ( P < 0.01). Compared with the model group, EWB significantly reduced the Zea-Longa five-point neurological deficit score ( P < .05, P < .001), improved rat survival rate ( P < .01, P <.001), increased activity distance ( P < .01) and activity time ( P < .01, P < .001), showing a significant therapeutic effect on spontaneous behavior and learning and memory impairments in rats. ELISA results demonstrated that EWB significantly reduced the expression levels of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α ( P < .01), leading to a marked reduction in neuroinflammation. Combined transcriptomics and metabolomics analyses identified SLC17A6, SLC6A11, SLC6A9, ADORA1, and GNG7 as key molecular targets of EWB. These targets modulate downstream pathways, including synaptic vesicle cycling, tyrosine metabolism, and glycerophospholipid metabolism, through inflammatory mediators. Furthermore, qRT-PCR and western blot analyses confirmed that EWB mitigates inflammation and inhibits relevant metabolic pathways by regulating the gene and protein expression of these core targets. Conclusion In summary, this study revealed that EWB reduces neuroinflammation and protects against ischemic stroke by modulating SLC17A6, SLC6A11, SLC6A9, ADORA1, GNG7, and the NF-κB signaling pathway, as well as regulating metabolites such as adenosine monophosphate and succinic acid.

Source: Dose-Response

DOI: 10.1177/15593258251409844

Authors: Hong Xiao, Limuge Che, Yiri Du, Hashen Bao

Institution: Inner Mongolia Medical University

Language: English

Topic: Medical Research and Treatments

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,650