Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity

Figures

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  Figure 1. The targets of AS-IV were used to establish the protein-protein regulation network. (A) The image of Astragali Radix. (B) 2-D structure of AS-IV. (C) 43 candidate targets of AS-IV were identified to establish the protein-protein regulation network. The blue nodes represent the protein targets of AS-IV, and the red node stands for the AS-IV.

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  Figure 2. The collective targets of AS-IV and oxaliplatin neurotoxicity were identified. (A) 1217 collective targets of oxaliplatin and neurotoxicity were identified to show targets of oxaliplatin neurotoxicity. (B) 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified. (C) These collective targets were used to establish the protein-protein regulation network. The blue nodes represent the protein targets, red node stands for oxaliplatin neurotoxicity, the yellow nod represents AS-IV. (D) These collective targets were used to establish the protein-protein interaction network based on String analysis. (E) The protein-protein interaction network used Cityscape 3.7.2 software for visual analysis. The larger node area and the darker color mean the more important in the network.

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  Figure 3. Effect of AS-IV administration on body weight, MWT and cold allodynia of oxaliplatin-induced rats. (A) Rats’ weights in different groups were recorded after 0, 7, 14, 21 and 28 days of oxaliplatin treatment. (B and C) The MWT and cold allodynia time were assessed in rats from different groups after 0, 7, 14, 21 and 28 days of oxaliplatin treatment. Data are the means ± SEM of three experiments. (n=10, ∆p<0.05, model group vs control group; #p<0.05: model group vs low-AS-IV group; ^p<0.05: model group vs medium-AS-IV group; &p<0.05: model group vs high-AS-IV group).

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  Figure 4. Effects of AS-IV administration on the sciatic nerve conduction velocity of oxaliplatin-induced rats. The MCV and SCV were detected in in rats from different groups at day 28 of oxaliplatin treatment. Data are the means ± SEM of three experiments. (n=10, *P<0.05, compared with model group; **P<0.01, compared with model group).

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  Figure 5. Effects of AS-IV administration on histological changes of oxaliplatin-induced rats. (A) HE staining was used to observe the histological changes of spinal cord tissues in different groups of rats. (B and C) Nissl staining was applied to detect the number of Nissl bodies of spinal cord tissues from different groups of rats. Data are the means ± SEM of three experiments. (n=10, **P<0.01, compared with model group).

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  Figure 6. Effects of AS-IV administration on inflammation of oxaliplatin-induced rats. (A and D) The relative IOD of TNF-α was determined by IHC analysis in spinal cord of the six groups. (B and E) The relative IOD of IL-6 was determined by IHC analysis in spinal cord of the six groups. (C and F) The relative IOD of IL-1β was determined by IHC analysis in spinal cord of the six groups. Data are the means ± SEM of three experiments. (n=10, *P<0.05, compared with model group; **P<0.01, compared with model group).

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  Figure 7. Effects of AS-IV administration on oxidative stress of oxaliplatin-induced rats. (A–D) The relative absorbance of MDA, SOD, CAT and GSH-Px of spin cord tissues in different groups were detected. Data are the means ± SEM of three experiments. (n=10, *P<0.05, compared with model group; **P<0.01, compared with model group).

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  Figure 8. Schematic representation of the proposed mechanism in AS-IV alleviating oxaliplatin neurotoxicity. Network pharmacology was used to analyze the key targets of AS-IV in the treatment of oxaliplatin neurotoxicity; animal experiments have confirmed that AS-IV can improve neurotoxicity of oxaliplatin by inhibiting the neuroinflammation and oxidative stress of spinal cord.