ArticleMediators of inflammation2026
Rougan Tongluo Decoction Initiates Neuroprotection Against Cerebral Ischemia by Activating the Endogenous SLC6A8-Creatine-EARS2 Mitochondrial Pathway.
Article in Mediators of inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Rougan Tongluo Decoction Initiates Neuroprotection Against Cerebral Ischemia by Activating the Endogenous SLC6A8-Creatine-EARS2 Mitochondrial Pathway.Mediators of inflammation · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
objectiveThe traditional Chinese medicine formula Rougan Tongluo Decoction (RGTL) was widely used to treat neurological injury after cerebral ischemia, though its specific underlying mechanisms remain unknown. This study investigates the mechanisms via which RGTL helps alleviate cerebral ischemic injury to provide theoretical support for its application in cerebral ischemia treatment.
methodsA middle cerebral artery occlusion reperfusion (MCAO/R) rat model was established and treated with RGTL, N-acetylcysteine (NAC), creatine, or sh-EARS2. Network pharmacology and metabolomics were conducted to analyze the key efficacy-related metabolites in the hippocampal tissue. An OGD/R cell model was constructed using PC12 cells and treated with creatine, RGTL-containing serum, sh-SLC6A8, and sh-EARS2. Neuronal damage in the hippocampal tissues was assessed using HE and Nissl staining. Neuronal cell viability, mitochondrial membrane potential, and ROS levels were measured using CCK8, JC-1, and DCFH-DA assays. Mitochondrial damage was determined using transmission electron microscopy. The expression of SLC6A8/EARS2 axis and mitochondrial-related proteins (cytochrome c [Cyt c]) was examined using RT-qPCR and Western blot.
resultsRGTL treatment reduced TNF-α, IL-6, and ROS levels while increasing ATP and JC-1 in brain tissues of MCAO/R rats, thereby alleviating mitochondrial damage. The neuroprotective effects of RGTL were more pronounced than those of NAC. Succinic acid and creatine were identified as active drug ingredients and differential metabolites that may mediate RGTL's therapeutic effects via MMP3, GAMT, SLC6A8, and CASP3. Silencing SLC6A8 abolished the protective effects of creatine against OGD/R-induced neuronal cell apoptosis and mitochondrial damage. Creatine could bind to the EARS2 protein. Cell and animal experiments demonstrated that silencing EARS2 blocked the therapeutic effects of creatine in OGD/R and MCAO/R models, reversing its inhibition of neuronal apoptosis and mitochondrial damage.
conclusionCreatine mediates the neuroprotective effects of RGTL by binding to EARS2, thus inhibiting mitochondrial damage and neuronal apoptosis to improve ischemic brain injury.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.