Deciphering Pharmacological Mechanism of Buyang Huanwu Decoction for Spinal Cord Injury by Network Pharmacology Approach

Objective The purpose of this study was to investigate the mechanism of action of the Chinese herbal formula Buyang Huanwu Decoction (BYHWD), which is commonly used to treat nerve injuries, in the treatment of spinal cord injury (SCI) using a network pharmacology method. Methods BYHWD-related targets were obtained by mining the TCMSP and BATMAN-TCM databases, and SCI-related targets were obtained by mining the DisGeNET, TTD, CTD, GeneCards, and MalaCards databases. The overlapping targets of the abovementioned targets may be potential therapeutic targets for BYHWD anti-SCI. Subsequently, we performed protein-protein interaction (PPI) analysis, screened the hub genes using Cytoscape software, performed Gene Ontology (GO) annotation and KEGG pathway enrichment analysis, and finally achieved molecular docking between the hub proteins and key active compounds. Results The 189 potential therapeutic targets for BYHWD anti-SCI were overlapping targets of 744 BYHWD-related targets and 923 SCI-related targets. The top 10 genes obtained subsequently included AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN. Fifteen signaling pathways were also screened out after enrichment analysis and literature search. The results of molecular docking of key active compounds and hub target proteins showed a good binding affinity for both. Conclusion This study shows that BYHWD anti-SCI is characterized by a multicomponent, multitarget, and multipathway synergy and provides new insights to explore the specific mechanisms of BYHWD against SCI.


Introduction
Spinal cord injury (SCI) is a group of disorders in which the integrity and continuity of the spinal cord are disrupted by trauma, tumor, hypoxia, inflammation, and other factors [1]. According to the World Health Organization (WHO) report, about 250,000 to 500,000 people worldwide suffer from SCI every year, and the population is mainly under 30 years old [2]. e Beijing SCI Epidemiology Survey Group reported in 2002 that the incidence of SCI in Beijing was about 60/10 6 , an increase of nearly 10 times compared to the late 1980s, and that the per capita hospitalization cost was 27819.3 CNY [3]. e high disability rate and high consumption of SCI have imposed a heavy burden on the families of patients and society, while how to protect and restore injured neurons after SCI has been considered a great challenge in clinical and experimental research [4]. ere is still a lack of effective treatment for SCI, but it is known that traditional Chinese medicine (TCM) has a long history and rich practical experience, which may be explored for the treatment of SCI [2]. Modern Chinese medicine scholars classify SCI as "Ti Duo" and "Wei Zheng" based on the TCM classics "Ling Shu Jing-Han Re Bing" and "Su Wen-Wei Lun" [3]. Based on the analysis of the etiology and pathogenesis of SCI by TCM, as well as the pathological changes of the damaged Governor Vessel and the symptoms corresponding to SCI, the main treatment of TCM is to unblock Governor Vessel and strengthen "Yang Qi," supplemented by tonifying the kidney and filling the essence, strengthening the tendons and bones, activating blood circulation and removing blood stasis, and warming the meridians [3]. Buyang Huanwu Decoction (BYHWD), recorded in "Yi Lin Gai Cuo" by Wang Qingren in the Qing Dynasty, has been used in China for hundreds of years to treat stroke-related disabilities and improve the recovery of neurological function [5]. e whole formula of BYHWD consists of seven herbs: Chishao (Radix Paeoniae Rubra), Chuanxiong (Rhizoma Chuanxiong), Danggui (Radix Angelicae Sinensis), Dilong (Pheretima), Huangqi (Radix Astragali), Honghua (Flos Carthami), and Taoren (Semen Persicae) [5]. Studies have shown that BYHWD may promote the repair of SCI by upregulating the expression of Notch1 gene [6], and BYHWD combined with bone marrow mesenchymal stem cells (BMSCs) transplantation can promote the recovery after SCI by saving axotomized red nucleus neurons in rats [4]. Although some progress has been made in the study of BYHWD for SCI, the complexity of herbal prescriptions with multiple components, targets, and pathways makes the study of the specific mechanism of action of BYHWD for SCI difficult to clarify.
In the last decade, with the development of modern multiomics theories such as genomics, proteomics, and metabolomics, the introduction of a systems biology perspective, and the application of bioinformatics, the concept of network pharmacology has emerged. According to the network basis of drug action, network pharmacology methods, including protein-protein interaction (PPI) network, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, are applied to infer the specific pathways of multimolecular drug action in the human body, which is consistent with the multicomponent, multitarget, and multipathway synergy of Chinese herbal medicine and helps to clarify the mechanism of action of BYHWD ( Figure 1).

Acquisition of BYHWD-Related Targets and SCI-Related
Targets.
e compounds related to BYHWD were obtained by searching "Chishao or CHI SHAO or Radix Paeoniae Rubra," "Chuanxiong or CHUAN XIONG or Rhizoma Chuanxiong," "Danggui or DANG GUI or Radix Angelicae Sinensis," "Dilong or DI LONG or Pheretima," "Huangqi or HUANG QI or Radix Astragali," "Honghua or HONG HUA or Flos Carthami," and "Taoren or TAO REN or Semen Persicae" in Traditional Chinese Medicine Systems Pharmacology (TCMSP, version 2.3, https://tcmspw.com/tcmsp. php) database [7], and then the active compounds that met the criteria (oral bioavailability (OB) ≥ 30 and drug-likeness (DL) ≥ 0.18) were further screened by the absorption, distribution, metabolism, and excretion (ADME) principle [8,9], and the corresponding target protein information of the active compounds was also obtained. Subsequently, by using the UniProt database (https://www.uniprot.org/) (species should be set to "Homo sapiens"), the target protein name is converted into the corresponding gene name and UniProt ID [10]. e compounds and targets related to BYHWD were also obtained directly by searching the above keywords in the BATMAN-TCM platform (http://bionet. ncpsb.org/batman-tcm/) according to the set criteria (score cutoff >25, adjusted P value < 0.05) [11]. Finally, the results of the two databases are summarized, integrated, and deduplicated to obtain BYHWD-related targets.

Acquisition of Potential erapeutic Targets for BYHWD
Anti-SCI. Potential therapeutic targets of BYHWD in the treatment of SCI should be derived from the overlapping targets of BYHWD-related targets and SCI-related targets obtained from the Venn online tool (http://www. bioinformatics.com.cn/). Subsequently, we used Cytoscape software (version 3.7.2) to construct a network diagram of "BYHWD-active compounds-target genes-SCI" [17].

Construction of PPI Network and Acquisition of Hub
Genes. PPI is composed of proteins that interact with each other to participate in various aspects of life processes such as biological signaling, regulation of gene expression, energy and material metabolism, and cell cycle regulation [18]. e potential therapeutic targets of BYHWD against SCI were analyzed by a PPI network using the STRING database (http://string-db.org/; version 11) with the species set to "Homo sapiens" and a confidence level greater than 0.4 [19]. Subsequently, the PPI network was visualized by Cytoscape software (version 3.7.2).

GO and KEGG Pathway Enrichment Analysis of Potential
erapeutic Genes for BYHWD Anti-SCI. R is commonly used for statistical analysis and plotting software, and its open-source and free features have been favored by many programming enthusiasts, resulting in the birth of many convenient and efficient packages, such as the 2 Evidence-Based Complementary and Alternative Medicine ClusterProfiler package for GO annotation and KEGG pathway enrichment analysis [22][23][24]. In this study, we used ClusterProfiler package (adjusted P value < 0.05) to explore the biological processes (BP), cellular components (CC), molecular functions (MF), and signaling pathways associated with BYHWD anti-SCI.

Molecular Docking of Hub Genes and Key Active
Compounds. Based on the previously mined BYHWD-related targets and related active compounds, the active compounds and herbs corresponding to the top 10 hub genes need to be sorted out. e interrelationship between "herbs in BYHWD-active compounds-top 10 hub genes" was visualized by a Sankey diagram (http://sankeymatic. com/). In the following, we will select key active compounds as small molecule ligands and corresponding large molecule receptors (proteins encoded by the top 10 hub genes) for molecular docking analysis. e raw files of key active compounds (MOL2 format) can be downloaded from PubChem database (https://pubchem.ncbi.nlm.nih.gov/), and the raw files of the top 10 core genes (PDB format) can be downloaded from the RCSB protein data (http://www. rcsb.org/), and after corresponding processing by AutoDock Tool [25], they are finally converted to PDBQT format for molecular docking in Pymol software (https://pymol.org/2/; version 2.4.1) [26]. e molecular docking score reflects the binding affinity, with smaller values representing higher affinity for the binding of small molecule ligands and large molecule receptors [27].

Acquisition Results of BYHWD-Related Targets and SCI-Related Targets.
A total of 775 compounds (BATMAN-TCM: 219; after deduplication: 189) in BYHWD were preliminarily retrieved from the TCMSP database and BATMAN-TCM platform (score cutoff >25; adjusted P value < 0.05), of which 119 (BATMAN-TCM: 8) were from Chishao, 189 (87) were from Chuanxiong, 125 (77) were from Danggui, 87 (23) were from Huangqi, 189 (22) were from Honghua, and 66 (2) were from Taoren. Relevant compounds and targets' information for Dilong was not retrieved in either database. After setting the ADME criteria (OB ≥ 30% and DL ≥ 0.18), a total of 103 active compounds (after removing duplicates and nontarget compounds: 60) were screened from the TCMSP database, of which 29 (After removing nontarget compounds: 14) were from Chishao, 7 (6) were from Chuanxiong, 2 (2) were from Danggui, 20 (17) were from Huangqi, 22 (17) were from Honghua, and 23 (19) were from Taoren. e BATMAN-TCM platform provides the gene names directly, while the TCMSP database first provides the target protein names of the active compounds and therefore needs to be converted to gene names via the UniProt database. Finally, after integrating the results of the two databases, we obtained 244 BYHWD-related active compounds and 744 BYHWD-related targets.

Acquisition Results of Potential erapeutic Targets for BYHWD Anti-SCI.
e overlapping targets of BYHWDrelated targets and SCI-related targets were considered as potential therapeutic targets for BYHWD anti-SCI. As shown in Figure 2, we screened the overlapping targets of both by constructing a Venn diagram, and a total of 189 targets were obtained. rough multiple databases mining and construction of the Venn diagram, we obtained BYHWD-related compounds and potential therapeutic targets for BYHWD anti-SCI and finally used Cytoscape software to construct a "BYHWD-active compounds-target genes-SCI" network ( Figure 3). In Figure 3, the lines between two nodes represent the existence of mutual relationships, and the larger the node is, the more relationships exist.

Acquisition Results of Hub Genes for BYHWD Anti-SCI and PPI Network Construction.
In the STRING database, we first set the species to "Homo sapiens" and then entered 189 potential therapeutic targets for BYHWD anti-SCI to obtain the PPI network (Figure 4(a)), which involved 189 nodes and 3717 edges. e obtained TSV files were then imported into Cytoscape software (version 3.7.2) for further analysis and visualization ( Figure 4(b)). To obtain the hub genes for BYHWD anti-SCI, based on the above the PPI network, we used the CytoHubba plug-in of Cytoscape software, which currently contains 12 topological analysis methods. We targeted the top 10 hub genes for BYHWD anti-SCI, and the results of the 12 algorithms each contained 10 genes. We integrated and analyzed the results to obtain a total of 45 different genes, which were then sorted by the number of algorithms to which they were attributed. Table 1 shows the basic information on hub genes for BYHWD anti-SCI. e top 10 hub genes (AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN) sorted are completely consistent with some algorithms (Degree, Closeness, and MNC) (Figure 4(c)).

Results of GO and KEGG Pathway Enrichment Analysis.
GO and KEGG pathway enrichment analysis are important tools to explore the biological processes and signal pathways involved in clinical drug therapy for diseases, as well as key genes. rough the ClusterProfiler package in R, we performed GO enrichment analysis on the 189 potential therapeutic targets for BYHWD anti-SCI and obtained 2842 GO items (after adjustment, P < 0.05), including 2567 BP items, 99 CC items, and 176 MF items. We combined the top 10 enrichment results for each of GO-BP, GO-CC, and GO-MF by a bar graph ( Figure 5). e basic information of the top 10 GO enrichment items is shown in Table 2.
In the same way, through the ClusterProfiler package in R, we performed KEGG pathway enrichment analysis on the 189 potential therapeutic targets for BYHWD anti-SCI and obtained 177 KEGG pathways (after adjustment, P < 0.05).   (hsa05222), Pancreatic cancer (hsa05212), Measles (hsa05162), Epstein-Barr virus infection (hsa05169), Nonalcoholic fatty liver disease (hsa04932), Influenza A (hsa05164), Endocrine resistance (hsa01522), Bladder cancer (hsa05219), Platinum drug resistance (hsa01524), and Apoptosis (hsa04210). e visualization of the abovementioned KEGG enrichment pathway is realized in Figure 6. More KEGG pathways were enriched, and another fine screening of the pathways was required. erefore, the SCI-related literature was searched in the PubMed database, and then the retrieved potentially relevant pathways were compared with the enriched 177 pathways, and finally, 15 relatively relevant pathways for SCI were obtained. Subsequently, we used Cytoscape software to visualize the network relationship between potential therapeutic targets for BYHWD anti-SCI and pathways (Figure 7). Table 3 shows the basic information of 15 pathways that may be relevant for SCI.

Results of Molecular Docking of Hub Genes and Key Active
Compounds. Sankey diagram was used to establish one-toone correspondence between the top 10 hub genes (AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN) for BYHWD anti-SCI and BYHWD-related compounds, providing the basis for the next molecular docking analysis. Among them, the gene that targets the most active compounds is TNF, and the key active compounds that target the most hub genes are quercetin and luteolin ( Figure 8). As seen in the Sankey diagram, 6 of the 33 active compounds (quercetin, luteolin, beta-carotene, kaempferol, baicalein, and beta-sitosterol) targeted more hub genes, so we decided to perform the molecular docking between these 6 active compounds and top 10 hub genes. e results of the molecular docking score are presented as a heat map (Figure 9), with a range of −6.4 to −10.9 kcal·mol −1 , representing the large molecule protein receptor (hub genes) that binds well to the small molecule ligand (key active compounds). As shown in Figure 10, the molecular docking process of each key active compound and its corresponding protein encoded by the hub gene with the best docking affinity was visualized using Pymol. Table 4 shows the basic information of active compounds targeting hub genes in BYHWD.

Discussion
According to the report of the National SCI Statistics Center, there are about 17,000 new cases of SCI in the United States each year, and the annual incidence of SCI is about 54 cases per million people [1]. Over the past century, advances in understanding the mechanisms of SCI have changed the clinical management strategies for SCI, including surgical procedures, supportive measures, and rehabilitative training that have improved neurological outcomes and reduced morbidity in SCI patients [1]. However, there is still a lack of effective treatments for SCI and thus has been stimulating the desire of researchers to explore and try to find effective treatments, including drugs, surgical methods, and rehabilitation programs. As we all know, TCM has a long history of being used to treat various diseases in China and other Asian countries [28]. Among them, BYHWD, Jisuikang, single herb, and Governor Vessel electroacupuncture have all been shown in relevant studies to be used in the treatment of SCI [4,5,[28][29][30]. BYHWD, which comes from Qing Dynasty medical classics, consists of seven herbs: Chishao, Chuanxiong, Danggui, Dilong, Huangqi, Honghua, and Taoren [5]. Based on the theory of TCM, Huangqi is the main ingredient in this Evidence-Based Complementary and Alternative Medicine formula, which has the function of tonifying Qi and nourishing blood, eliminating blood stasis without harming the proper function; Danggui is the secondary herb, which has the effect of invigorating blood and harmonizing blood; Chishao, Chuanxiong, Dilong, Honghua, and Taoren are the adjuvant herbs in this formula; all the five herbs have the function of activating blood circulation and removing blood stasis, promoting the flow of Qi and blood circulation; the combination of the five herbs not only activates blood circulation and removes blood stasis but also helps the Qi and blood that the main herbs benefit to reach the whole body [3,31]. Studies have shown that BYHWD in combination with neural stem cells (NSCs) attenuates the process of demyelination or improves the recovery of myelin and exerts a synergistic effect on the neurological function recovery [5]. It has been shown that BYHWD restores hindlimb motor function in rats with SCI, and the neuroprotective effect is associated with the regulation of apoptosis-related protein expression [32]. BYHWD rescues axotomized neurons and promotes functional recovery after  MMP10 Stromelysin-2 (6) and (7)   showed that BYHWD protected the injured neurons and promoted functional recovery after SCI in rats [33]. However, since the specific mechanism of BYHWD for the treatment of SCI is still unclear due to its complex composition and wide range of effects, we decided to use a network pharmacology approach to investigate in this study and to lay the foundation for the next in-depth study.
In the first step, BYHWD-related compounds and related targets were obtained. We obtained relevant compounds and targets by mining two herbal-related databases, TCMSP and BATMAN-TCM. e mining methods of these two databases are different: TCMSP database (ADME principle: OB ≥ 30 and DL ≥ 0.18) first obtains BYHWDrelated compounds, then obtains related target proteins, and finally needs to be converted into standard gene names by UniProt database; BATMAN-TCM platform (score cutoff >25, adjusted P value <0.05) directly obtains BYHWD-related compounds and target genes. e screening process of TCMSP database is divided into five steps:  e results of the two databases were integrated and deduplicated to finally obtain 244 BYHWD-related active compounds and 744 BYHWDrelated targets. In the second step, a total of 923 SCI-related targets were acquired by mining 5 disease databases, including DisGeNET (number: 84), TTD (number: 5), CTD (number: 553), GeneCards (number: 432), and MalaCards (number: 19). Next, the Venn diagram of BYHWD-related targets and SCI-related targets was plotted by the website online tool to obtain 189 potential therapeutic targets of BYHWD against SCI.

Evidence-Based Complementary and Alternative Medicine
In total, Cytoscape software was used four times in this study: (1) the "BYHWD-active compounds-target genes-SCI" network was constructed, involving 410 nodes and 1571 interactions; (2) the PPI network obtained from the STRING database was reconstructed here, involving 189 nodes and 3717 interactions; (3) the top 10 hub genes (AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN) of BYHWD against SCI were obtained based on 12 topological analysis methods (Degree, MCC, Stress, Clus-teringCoefficient, EcCentricity, BottleNeck, Closeness, Radiality, Betweenness, EPC, DMNC, and MNC) contained in the CytoHubba plug-in; (4) the "potential therapeutic targets-pathways" network was constructed, involving 347 nodes and 2650 interactions. Studies have shown that the protein encoded by TP53 and other factors regulate the regeneration, germination, and functional recovery of axons after central nervous system injury [34]; the rapid upregulation of CASP3 mRNA seen after SCI in rats may be associated with cell death in the spinal cord [35]; inflammatory mediators such as TNF-α and IL6 mediate the recruitment of inflammatory cells to the site of injury and by targeting these cytokines may be a potential strategy to reduce secondary injury in SCI [36,37]; by targeting MAPK1, the overexpression of miRNA-433-5p protects motor dysfunction and inflammation after SCI [38].
e Sankey diagram was used once, mainly to show the correspondence between the top 10 hub genes and the corresponding active compounds contained in BYHWD (quercetin, luteolin, beta-carotene, kaempferol, baicalein, beta-sitosterol, carvacrol, O-cresol, anisic acid, 1-methyl-2dodecyl-4-(1h)-quinolone, 4-ethylresorcinol, angelicin, astragaloside I, astragaloside II, caffeic acid dimethyl ether, cibarian, cordycepin, dihydropinosylvin, dodecenoic acid, ellagic acid, ethyl-P-methoxycinnamate, formononetin, linoleic acid, M-cresol, M-ethylphenol, O-ethylphenol, oleic Evidence-Based Complementary and Alternative Medicine acid, paeoniflorin, P-cresol, P-ethylphenol, sebiferic acid, sucrose, and thymol). Among them, quercetin targeted six hub genes, luteolin targeted six hub genes, beta-carotene targeted five hub genes, kaempferol targeted four hub genes, baicalein targeted three hub genes, beta-sitosterol targeted two hub genes, anisic acid targeted two hub genes, and the others targeted one hub gene. e experimental results showed that quercetin exerts a protective effect on the spinal cord by inhibiting the activation of the p38MAPK/iNOS signaling pathway in SCI rats and subsequently regulating Figure 7: Potential therapeutic targets-pathways" network. e blue diamond represents the top 10 hub genes; the cyan rectangle represents the potential therapeutic targets for BYHWD anti-SCI; the yellow ellipse represents potential SCI-related pathways supported by literature; the green ellipse represents possible pathways related to SCI.  [39]; the combination of luteolin and palmitoylethanolamide reduced autophagy in SCI [40]; beta-carotene effectively reduced the course of secondary damage events after SCI by blocking NF-κB pathway activation [41]; baicalein may alleviate the harm caused by SCI by activating PI3K and inducing autophagy to reduce neuronal apoptosis [42]. Based on the results of the Sankey diagram, we performed molecular docking of the top 10 genes and the top 6 compounds in terms of the number of targeted genes (quercetin, luteolin, beta-carotene, kaempferol, baicalein, and beta-sitosterol). e results of molecular docking of 60 cohorts of hub target proteins and key active compounds showed a good binding affinity for both. We used R software twice, once to present the scores of the above molecular docking as a heat map, and another time to perform GO and KEGG pathway enrichment analysis using the ClusterProfiler package. e top 10 results of the GO enrichment analysis of 189 potential therapeutic targets for BYHWD anti-SCI, based on the adjusted P value (from small to large), are as follows:       e first 20 results of the (adjusted P value based) KEGG pathway enrichment analysis of 189 potential therapeutic targets of BYHWD against SCI have been presented, and we screened the enriched pathways again to find possible relevant pathways for SCI. By searching the relevant literature, we screened a total of 15 pathways with strong relevance, as follows: AGE-RAGE signaling pathway in diabetic complications (hsa04933) [43], TNF signaling pathway (hsa04668), Apoptosis (hsa04210) [44], Pathways of neurodegeneration-multiple diseases (hsa05022), Toll-like receptor signaling pathway (hsa04620) [45], PI3K-Akt signaling pathway (hsa04151) [46], HIF-1 signaling pathway (hsa04066) [47], MAPK signaling pathway (hsa04010) [48], NF-kappa B signaling pathway (hsa04064) [49], EGFR tyrosine kinase inhibitor resistance (hsa01521) [50], JAK- Evidence-Based Complementary and Alternative Medicine STAT signaling pathway (hsa04630) [51], Wnt signaling pathway (hsa04310) [43], AMPK signaling pathway (hsa04152) [44], and mTOR signaling pathway (hsa04150) [46]. e above pathways and hub genes are not in a disconnected relationship; rather, many hub genes are important components of some of the pathways. Taking PI3K-Akt signaling pathway as an example, it contains AKT1, MAPK1, IL6, TP53, and VEGFA. Based on the results of the above network pharmacological analysis, we hypothesize that the key active compounds of BYHWD may exert anti-SCI effects through the above pathways and hub genes.

Limitations.
is study still has some limitations. First, the corresponding experimental validation is lacking. Second, the compounds, targets, and pathways contained in these databases may not be exhaustive. Finally, compounds screened based on ADME principles may be missing other important compounds.

Future Perspectives.
is study uncovered the multicompound, multitarget, and multipathway characteristics of BYHWD through a network pharmacology approach. Among them, the key compounds include quercetin, luteolin, beta-carotene, kaempferol, baicalein, and beta-sitosterol; the hub genes include AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN; and the important pathways are the 15 related pathways mentioned above. ese results clearly give a general direction for SCIrelated researchers, and there is no doubt that the anti-SCI mechanism of BYHWD is much more than the abovementioned research directions, and we will find more accurate targets and pathways while exploring them one by one.

Conclusion
Using a network pharmacology approach, we explored the potential mechanism of BYHWD as a classical herbal formula for treating nerve injury in the treatment of SCI. e top 10 core genes among the potential therapeutic targets for BYHWD anti-SCI include AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN. Key active compounds of BYHWD against SCI include quercetin, luteolin, beta-carotene, kaempferol, baicalein, and beta-sitosterol. In addition, combining the KEGG pathway enrichment results and reviewing SCI-related literature, we obtained 15 SCI potentially relevant pathways, mainly including PI3K-Akt signaling pathway, MAPK signaling pathway, NF-kappa B signaling pathway, TNF signaling pathway, Apoptosis, Toll-like receptor signaling pathway, HIF-1 signaling pathway, JAK-STATsignaling pathway, Wnt signaling pathway, AMPK signaling pathway, and mTOR signaling pathway. e above analysis results demonstrated the multitarget, multicomponent, and multipathway characteristics of BYHWD in treating SCI, which laid the foundation for us to carry out specific experimental validation in the next step, and provided new ideas for researchers dedicated to the treatment of SCI with herbal extracts.

Data Availability
e data used to support the findings of this study are included within the article.

Disclosure
Zhencheng Xiong and Feng Yang are joint first authors.

Conflicts of Interest
e authors declare that there are no conflicts of interest regarding the publication of this article.