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Eucommiae cortex (EC) and Achyranthis radix (AR) are herbal medicines widely used in combination for the treatment of intervertebral disc herniation (IDH). The mechanisms of action of the herbal combination have not been understood from integrative and comprehensive points of view. By adopting network pharmacological methodology, we aimed to investigate the pharmacological properties of the EC-AR combination as a therapeutic agent for IDH at a systematic molecular level. Using the pharmacokinetic information for the chemical ingredients of the EC-AR combination obtained from the comprehensive herbal drug-associated databases, we determined its 31 bioactive ingredients and 68 IDH-related therapeutic targets. By analyzing their enrichment for biological functions, we observed that the targets of the EC-AR combination were associated with the regulation of angiogenesis; cytokine and chemokine activity; oxidative and inflammatory stress responses; extracellular matrix organization; immune response; and cellular processes such as proliferation, apoptosis, autophagy, differentiation, migration, and activation. Pathway enrichment investigation revealed that the EC-AR combination may target IDH-pathology-associated signaling pathways, such as those of cellular senescence and chemokine, neurotrophin, TNF, MAPK, toll-like receptor, and VEGF signaling, to exhibit its therapeutic effects. Collectively, these data provide mechanistic insights into the pharmacological activity of herbal medicines for the treatment of musculoskeletal diseases such as IDH.

Network Pharmacological Dissection of the Mechanisms of Eucommiae Cortex-Achyranthis Radix Combination for Intervertebral Disc Herniation Treatment