Potential Mechanisms of Jingtong Granules in Cervical Degeneration: An Integrative Multiomics and Computational Study.

Abstract

Jingtong Granules is a widely used Chinese patent medicine approved by China's National Medical Products Administration for cervical spondylotic radiculopathy, but its systems-level mechanism remains insufficiently defined. This study investigated its potential mechanisms in cervical degeneration using a staged integrative framework. Candidate targets were screened and evaluated using transcriptomic, genetic, and structural evidence. Intersecting compound targets from four databases with cervical-spondylosis-associated genes identified 40 multi-source-supported drug-disease targets and 17 hub genes. The hub module was dominated by inflammatory cytokines, matrix-remodeling molecules, and central signaling regulators, with enrichment concentrated in PI3K-Akt, TNF, IL-17, and AGE-RAGE signaling. MMP9 showed the strongest pathway association, exploratory blood-discriminative potential, and nominal genetic support for spondylosis risk. AKT1 was the highest-degree signaling hub, and molecular dynamics simulations supported the stability of its quercetin and kaempferol complexes. Single-cell analysis placed the hub module in relevant disc-cell populations. However, these findings may be confounded by age because patient and control age ranges did not overlap. Overall, this study prioritizes an AKT1/MMP9-centered inflammatory and extracellular-matrix-remodeling module as a patient-grounded candidate mechanism of Jingtong Granules in cervical degeneration. Experimental validation in adequately powered disease-specific cohorts is warranted.

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