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Peer-reviewedCC BY 4.0Frontiers in Neurology

Traditional Chinese medicine-related interventions and the cGAS–STING axis in neuroinflammation: disease contexts and mechanisms of action

  1. 1Pengzhou Hospital of Traditional Chinese Medicine (Peony New City Campus)

Abstract

Research on traditional Chinese medicine (TCM)-related interventions has shifted from overall phenotypic effects to defined neuroimmune targets. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis connects cytosolic DNA sensing with host defense and sterile inflammatory injury, but the functional direction of this pathway changes with disease context. This review organizes preclinical findings by pathological setting and site of action. It examines herbal formulas and natural compounds, followed by acupuncture, electroacupuncture, and related delivery systems. Several sterile injury models associate benefit with reduced pathway-related inflammation. Acute sleep deprivation provides an example of protection accompanying restored STING signaling. Early herpes simplex virus infection follows a different pattern: restoration of suppressed antiviral signaling improves host defense. In acute postoperative pain and cancer-induced bone pain models, increased STING-IFN-I signaling accompanies electroacupuncture-induced analgesia. Some interventions reduce mitochondrial DNA stimulation. Others act on cGAS or STING, with separate studies targeting STING trafficking. Downstream inflammatory and cell-death responses form the final level. Mechanistic attribution is strongest when genetic or pharmacological perturbation links pathway change to functional outcome; direct binding has been demonstrated for a small group of compounds. These findings support a context-sensitive framework for interpreting modulation direction that requires validation within individual disease models. Clinical translation will depend on reproducible formulation composition, effective brain exposure, and safety.

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BibTeX
@article{zhang2026traditional,
  title = {{Traditional Chinese medicine-related interventions and the cGAS–STING axis in neuroinflammation: disease contexts and mechanisms of action}},
  author = {Cunlong Zhang and Qingqing Li},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1979957},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1979957/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Traditional Chinese medicine-related interventions and the cGAS–STING axis in neuroinflammation: disease contexts and mechanisms of action
AU  - Cunlong Zhang
AU  - Qingqing Li
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1979957
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1979957/full
AB  - Research on traditional Chinese medicine (TCM)-related interventions has shifted from overall phenotypic effects to defined neuroimmune targets. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis connects cytosolic DNA sensing with host defense and sterile inflammatory injury, but the functional direction of this pathway changes with disease context. This review organizes preclinical findings by pathological setting and site of action. It examines herbal formulas and natural compounds, followed by acupuncture, electroacupuncture, and related delivery systems. Several sterile injury models associate benefit with reduced pathway-related inflammation. Acute sleep deprivation provides an example of protection accompanying restored STING signaling. Early herpes simplex virus infection follows a different pattern: restoration of suppressed antiviral signaling improves host defense. In acute postoperative pain and cancer-induced bone pain models, increased STING-IFN-I signaling accompanies electroacupuncture-induced analgesia. Some interventions reduce mitochondrial DNA stimulation. Others act on cGAS or STING, with separate studies targeting STING trafficking. Downstream inflammatory and cell-death responses form the final level. Mechanistic attribution is strongest when genetic or pharmacological perturbation links pathway change to functional outcome; direct binding has been demonstrated for a small group of compounds. These findings support a context-sensitive framework for interpreting modulation direction that requires validation within individual disease models. Clinical translation will depend on reproducible formulation composition, effective brain exposure, and safety.
SN  - 1664-2295
ER  -