Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM

• Published in: Phytomedicine (Stuttgart) 2024-04, Vol.126, p.155073-155073, Article 155073
• Main Authors: Li, Zhuo-yao, Dai, Yu-xiang, Wu, Zi-ming, Li, Gan, Pu, Pei-min, Hu, Cai-wei, Zhou, Long-yun, Zhu, Ke, Shu, Bing, Wang, Yong-Jun, Cui, Xue-jun, Yao, Min
• Format: Article
• Language: English
• Subjects: Animal Experimentation; Animals; Cervical spondylotic myelopathy; Chromatography, Liquid; Drugs, Chinese Herbal - pharmacology; Ginsenosides; Ginsenosides - pharmacology; Humans; Interleukin-17; Molecular Docking Simulation; Myeloid Differentiation Factor 88; Network Pharmacology; Neuroinflammation; Neuroinflammatory Diseases; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphatidylinositol 3-Kinases; Rats; Spinal Cord Compression; Spinal Cord Diseases; Tandem Mass Spectrometry; Toll-Like Receptor 4; UPLC-MS
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2023.155073

Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. The results of network pharmacology indicate