ArticleNeurochemical research2026
Cinchonidine Ameliorates Traumatic Brain Injury-Related Neurobehavioral Deficits via the SRC/RAF1/NF-κB Pathway to Attenuate Mitochondrial Dysfunction.
Article in Neurochemical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Cinchonidine (CD), a metabolite derived from gut microbiota, shows promise in protecting against traumatic brain injury (TBI), where mitochondrial dysfunction is a key driver of secondary damage. Using a mouse model of controlled cortical impact (CCI) and an in vitro primary neuron injury model, CD administration resulted in improved physiological status (weight recovery, stabilized heart rate) and behavioral outcomes (increased travel distance and speed) in TBI mice. Histological analysis showed reduced hippocampal neuronal damage, decreased pro-inflammatory cytokines (interleukin‑1β, interleukin‑6, and tumor necrosis factor‑α), and upregulated blood-brain barrier tight-junction proteins (Claudin-5, Occludin, zonula occludens‑1). Mitochondrial function was improved, evidenced by increased mitochondrial DNA copy number, elevated expression of translocase of outer mitochondrial membrane 20 and cytochrome c oxidase subunit IV, and restoration of mitochondrial membrane potential. In addition, CD attenuated TBI-induced changes in mitochondrial dynamics and biogenesis, restoring the phosphorylated dynamin-related protein 1 (p-DRP1)/DRP1 ratio and the expression of mitofusin 1/2 (MFN-1/2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), while reducing mitochondrial DRP1. Network pharmacology identified proto‑oncogene tyrosine‑protein kinase Src (SRC) as a key target, validated by stable binding in molecular docking and drug affinity responsive target stability assays. Furthermore, cellular thermal shift assays demonstrated a direct interaction between CD and SRC. CD treatment suppressed the activation of the SRC/RAF proto-oncogene serine/threonine-protein kinase (RAF1)/nuclear factor kappa B (NF-κB) signaling axis, as evidenced by reduced phosphorylation of SRC and p65, along with decreased expression of RAF1 and cleaved Caspase-3. Crucially, SRC knockdown mimicked CD's protection, while SRC overexpression abolished its benefits. These findings suggest that CD ameliorates post-TBI mitochondrial dysfunction, neuroinflammation, and neuronal damage by inhibiting SRC kinase activity and its downstream RAF1/NF-κB signaling pathway. Thus, CD may represent a promising SRC-targeted neuroprotective strategy for TBI.
Indexed as
Identifiers
42900453What OpenQuestion 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 OpenQuestion graph.