Abstract
ABSTRACT
Rationale
Jingtong Granules is a clinically approved seven‐herb formula for CSR, a condition in which radicular pain is sustained partly by inflammatory and immune processes, yet the immune‐cellular state of CSR and the immune‐level mechanism of the formula remain poorly defined.
Methods
Using peripheral‐blood transcriptomes from GSE223227 (7 controls, 9 CSR, and 30 degenerative cervical myelopathy), we profiled nine immune lineages by signature scoring, prioritized CSR‐associated features with six machine‐learning methods under permutation‐based specificity testing, localized signature genes on the Human Protein Atlas sorted immune‐cell reference, and linked the immune program to mass‐spectrometry‐confirmed constituents of Jingtong Granules by network pharmacology, molecular docking, molecular dynamics, and MM‐GBSA. Two‐level Mendelian randomization against cervical‐specific FinnGen endpoints tested genetic causal directionality.
Results
CSR blood showed a bidirectional immune‐rebalancing pattern: reduced NK‐cell activity (
p
= 0.0164), increased M1‐macrophage activity (
p
= 0.0311), and directionally higher neutrophil and lower CD8‐cytotoxic scores. The neutrophil/myeloid effector program discriminated CSR from controls (AUROC 0.79), exceeding a size‐matched random‐panel null, whereas a generic
NF‐κB/TNF
panel performed near chance; a composite rebalancing score reached a preliminary AUROC of 0.90 (95% CI 0.71–1.00). Network pharmacology nominated
MPO
as a formula‐associated immune target, whereas patient‐upregulated, neutrophil‐localized
ELANE
and
CTSG
were prioritized as structurally tractable granule enzymes. The validated quality markers nodakenin and paeoniflorin docked favorably to
ELANE
and
CTSG
and remained in their catalytic pockets during molecular dynamics, with MM‐GBSA binding free energies of −16.0 to −33.5 kcal/mol. Both markers also showed favorable drug‐like physicochemical profiles. Mendelian randomization gave no support for an upstream genetic‐causal role of the myeloid‐skewed immune state in cervical disk disorders or radiculopathy.
Conclusions
These exploratory, single‐cohort findings characterize CSR peripheral blood as myeloid‐skewed and cytotoxic‐attenuated and nominate a traceable constituent‐to‐enzyme hypothesis in which mass‐spectrometry‐confirmed Jingtong Granules markers may engage patient‐upregulated neutrophil granule enzymes, warranting replication and experimental validation.