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ORIGINAL ARTICLE
Year : 2023 | Volume
: 9
| Issue : 4 | Page : 419-429
Elucidation of immune regulation mechanism of renshen guben oral liquid by network pharmacology and molecular docking
Ying-Ying Tan1, Ying-Ying Liu1, Jing-Yuan Zhang1, Jia-Lin Li1, Pei-Zhi Ye2, Antony Stalin3, Xiao-Tian Fan1, Zhi-Hong Huang1, Bing Li4, Chao Wu1, Shan Lu1, Zhi-Shan Wu1, Xiao-Meng Zhang1, Guo-Liang Cheng4, Jia-Rui Wu1, Yan-Fang Mou4
1 Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
2 Traditional Chinese Medicine Department, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
3 Department of Bioinformatics, Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China
4 Department of Traditional Chinese Medicine, State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi, China
Correspondence Address:
Dr. Jia-Rui Wu
Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang, Beijing 100 029
China
Yan-Fang Mou
State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi
China
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.391113
Objective: To investigate the mechanism of Renshen Guben oral liquid (RSGB) enhancing immune function. Materials and Methods: Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB. Results: A total of 112 active compounds of RSGB were found, and 501 targets were predicted. Furthermore, 2974 immune targets were obtained from UniProt and NCBI Gene databases, and 111 common targets of RSGB and immunity were obtained. Among them, interleukin (IL) 6, tumor necrosis factor, AKT1, VEGFA, STAT3, MAPK1, SRC, EGFR, IL1B, and PTGS2 might be the key targets for RSGB to improve immunity. ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway. Furthermore, this study preliminarily explored the mechanism of RSGB improving menopausal syndrome, polycystic ovary syndrome, and cancer-related fatigue by enhancing immunity. Conclusions: RSGB can improve the body's immunity through multicomponent, multitarget, and multipathway. In addition, RSGB can also improve the immune capacity of the body to assist in the treatment of diseases, which has great potential as an immunomodulator.
Keywords: Immunity, molecular docking, network pharmacology, Renshen Guben oral liquid
With the acceleration of the rhythm of life and enhancement of the sense of competition, people's life and work are irregular, mental stress is great, and the body is in an unhealthy state, which leads to the decline of the body's immunity.[1] In addition, genetic genes, age, mood and other factors affect human immunity.[2],[3] Abnormal immunity is associated with most diseases. For example, in novel coronavirus (SARS-CoV-2) infections in late 2019, the elderly are more susceptible to infection due to immunosenescence and have a higher probability of developing into severe cases.[4],[5] Studies have indicated that with the gradual growth of age, human immune capacity gradually decreases.[6] Moreover, the incidence and frequency of tumors and diseases gradually increase, so immunocompromised patients will increase the risk of infection with other diseases. Modern medicine believes that the human immune system composed of immune organs, immune cells, and immunoactive substances, can regulate immune functions, thereby effectively preventing the occurrence of various diseases. Traditional Chinese medicine (TCM) is rich in resources and has a long history. Long-term clinical practice shows that it has a definite curative effect; TCM tonics are often used to boost the body's immunity and prevent and treat diseases.[7]
Renshen Guben oral liquid (RSGB) consists of ten herbs, including Panax ginseng C. A. Mey. (Ginseng Radix et Rhizoma; Renshen), Rehmannia glutinosa Libosch. (Rehmanniae Radix; Dihuang), R. glutinosa Libosch. (Rehmanniae Radix Praeparata; Shudihuang), Paeonia suffruticosa Andr. (Moutan Cortex; Mudanpi), Poria cocos (Schw.) Wolf (Poria; Fuling), Cornus officinalis Sieb. et Zucc. (Cornifructus; Shanzhuyu), Dioscorea opposita Thunb. (Dioscoreae Rhizoma; Shanyao), Alisma orientale (Sam.) Juzep. (Alismatis Rhizoma; Zexie), Asparagus cochinchinensis (Lour.) Merr. (Asparagi Radix; Tiandong), and Ophiopogon japonicus (L. f) Ker-Gawl. (Ophiopogonis Radix; Maidong). Studies have found that the ten herbs in this prescription all have immunomodulatory effects, and the main components that regulate the body's immunity are polysaccharides and saponins.[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] It belongs to the tonic Chinese patent medicine, which can regulate the immune system and enhance immunity. It is often used in the clinical auxiliary treatment of menopausal syndrome (MPS), polycystic ovary syndrome (PCOS), cancer-related fatigue (CRF), chronic bronchitis, pulmonary syndrome, tuberculosis, and other diseases, and has definite curative effects. Existing studies cannot elucidate the mechanism of the immune regulation of RSGB. Therefore, exploring the immunoregulatory mechanism of RSGB is of great significance for the clinical application of RSGB. Based on the overall concept of TCM and the theory of systems biology, this study uses network pharmacology to explore the targets and related signaling pathways of the immune regulation mechanism of RSGB, which provides an important theoretical basis for the clinical application of RSGB. The corresponding workflow is shown in [Figure 1].
Figure 1: The workflow of this study. TCM: Traditional Chinese medicine, RSGB: Renshen Guben oral liquid, PPI: Protein-protein interaction, KEGG: Kyoto Encyclopedia of Genes and Genomes, CRF: Cancer-related fatigue, PCOS: Polycystic ovary syndrome Materials and Methods Data preparation
Active compounds of Renshen Guben oral liquid
With oral bioavailability ≥30% and drug likeness ≥0.18 as screening conditions, the active compounds of Renshen, Shudihuang, Mudanpi, Fuling, Shanzhuyu, Shanyao, Zexie, and Tiandong were collected from the TCMSP database (https://tcmspw.com/tcmsp.php).[18] Since the TCMSP database does not contain the related chemical components of Dihuang and Maidong, the chemical constituents of the two herbs were searched in the BATMAN-TCM database (http://bionet.ncpsb.org/batman-tcm/)[19] with a score cutoff ≥20 and P value cutoff <0.05 as screening conditions. The search in the above two databases revealed that the numbers of active compounds from Renshen, Shudihuang, Mudanpi, Fuling, Shanzhuyu, Shanyao, Zexie, Tiandong, Dihuang, and Maidong were 22, 2, 11, 15, 20, 16, 10, 9, 2, and 18, respectively. According to the relevant literature, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Re, and paeonol are relatively high in RSGB, and pharmacological studies have found that they have immunomodulatory effects.[11],[20],[21],[22],[23],[24] Therefore, they were retained as the active components of RSGB and contained 112 active compounds.
Targets of Renshen Guben oral liquid
The PubChem database (https://pubchem.ncbi.nlm.nih.gov/)[25] and the Swiss TargetPrediction database (http://www.swisstargetprediction.ch/)[26] were used to predict targets. When the SMILES information of the active compounds was not available from the PubChem database, the structure of the compound was directly drawn on the Swiss TargetPrediction database to predict targets. Based on PubChem and Swiss TargetPrediction database, 501 potential targets of active components in RSGB were identified.
Targets of immunity
With “immunity” as the keyword, the UniProt database (https://www.uniprot.org/)[27] and the NCBI Gene database (https://www.ncbi.nlm.nih.gov/gene)[28] were used to search for targets, and 1159 and 792 immune targets were obtained, respectively. After integrating the two databases, a total of 2974 immune-related targets were obtained.
Targets of disease
Using “menopausal syndrome,” “polycystic ovary syndrome,” and “cancer-related fatigue” as keywords, the DisGeNET database (https://www.disgenet.org/)[29] and the GeneCards database (https://www.genecards.org/)[30] were used to collect disease targets. After integrating the results of the two databases, the numbers of related targets of MPS, PCOS, and CRF were 3408, 1854, and 2787, respectively.
ClueGO and Kyoto Encyclopedia of Genes and Genomes Analysis
ClueGO v2.5.7 (Laboratory of Integrative Cancer Immunology, Paris, France), a plug-in of Cytoscape that can be used to decipher the gene ontology (GO) annotation network of functional groups,[31] was used for GO analysis for common targets of RSGB and immunity with screening condition P ≤ 0.05.
The DAVID v6.8 (Frederick National Laboratory, Frederick, USA) (https://david.ncifcrf.gov/home.jsp)[32] was used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for common targets of RSGB, immunity, and disease. The screening condition was P < 0.05 and FDR <0.05.
Network construction
(1) The drug-compound-target network of RSGB was constructed by connecting herbs, active compounds, and targets; (2) The protein-protein interaction (PPI) network of common targets was constructed by analyzing the STRING database (https://www.string-db.org/).[33] (3) The drug-compound-target-pathway network of RSGB related to immunity was constructed by connecting drugs, key compounds, key targets, and key pathways. All networks were constructed by Cytoscape 3.7.2, a bioinformatics analysis software mainly used for network visualization and analysis.[34]
Molecular docking
The two-dimensional structures of key compounds were downloaded from the PubChem database and converted to three-dimensional (3D) structures using Chem 3D 19.0.0.22. The RCSB PDB database (http://www1.rcsb.org/)[35] was used to download the structure of key targets. AutoDock 4.2 and AutoDock Vina 1.1.2 were used for molecular docking according to published methods,[36] and PyMOL 1.7.4.5 was used to visualize the results.
ResultsImmune regulation mechanism of Renshen Guben oral liquid
Drug-compound-target network
Details of the 112 compounds in RSGB. The drug-compound-target network of RSGB contains 615 nodes and 3356 edges, as shown in [Figure 2]a. According to the degree of compounds in the network and the corresponding literature reports, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Re, paeonol, (+)-catechin, quercetin, dehydroeburicoic acid, kaempferol, and arachidonate were considered as the key active components of RSGB in regulating immunity. Moreover, it shows that RSGB plays an immunomodulatory role through multiple compounds and targets.
Figure 2: (a) Drug-compound-target network of RSGB. (b) Venn diagram of common targets of RSGB and immunity. (c) PPI network of common targets of RSGB and immunity. RSGB: Renshen Guben oral liquid, PPI: Protein-protein interactionProtein-protein interaction network of common targets of Renshen Guben oral liquid and immunity
Jvenn (http://www.bioinformatics.com.cn/static/others/jvenn/index.html)[37] was used to intersect the targets of RSGB and immunity targets, and 111 common targets were obtained, as shown in [Figure 2]b. The PPI network consists of 110 nodes (the degree value of AMY1A is 0, so the node is deleted) and 1295 edges, as shown in [Figure 2]c. The proteins with the 10 highest degree values were interleukin (IL) 6, tumor necrosis factor (TNF), AKT1, VEGFA, STAT3, MAPK1, SRC, EGFR, IL1B, and PTGS2. These high-degree proteins play key roles in the whole network, which may be the key targets in the immune regulation process of RSGB.
ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis
To elucidate the mechanism of action of 111 common targets, ClueGO was used to identify the biological interpretation and correlation of functional groups in biological networks. The results were divided into four parts: biological processes, immune system processes, cellular components, and molecular functions. According to the ClueGO analysis, the biological processes of the RSGB in the regulation of immunity were mainly included in four groups: regulation of response to external stimulus, positive regulation of internal signal transmission, response to lipids, and T cell activation [Figure 3]a. The immune system processes mainly consisted of four groups, including leukocyte differentiation, T cell activation, T cell promotion, and positive regulation of immune response [Figure 3]b. The cellular components of the targets were mainly associated with the vascular lumen, membrane raft, host cell part, and transferase complex that transfers phosphorus-containing groups [Figure 3]c. The molecular functions of the targets were mainly positive regulation of protein serine/threonine kinase activity, transcription factor binding, and positive regulation of lipase activity [Figure 3]d.
Figure 3: (a) Representative biological process interactions among targets. (b) Representative immune system process interactions among targets. (c) Representative cellular component interactions among targets. (d) Representative molecular function interactions among targetsA total of 105 pathways were obtained by KEGG analysis (P < 0.05 and FDR < 0.05). According to the P value, the first 15 enrichment pathways are listed, mainly involving pathways in cancer, the HIF-1 signaling pathway, the PI3K-Akt signaling pathway, pancreatic cancer, etc., The R software ggplot2 package (http://sangerbox.com/Tool) was used to draw a bubble diagram, as shown in [Figure 4]a. By retrieving the KEGG pathway database (https://www.genome.jp/kegg/pathway.html),[38] 12 signaling pathways directly related to the immune system were screened, including B cell receptor signaling pathway, chemokine signaling pathway, and T cell receptor signaling pathway. It is suggested that these 12 signaling pathways are the key pathways of RSGB in regulating the immune process, as shown in [Figure 4]b.
Figure 4: KEGG analysis of common targets of RSGB and immunity. (a) The first 15 pathways with the lowest P value. (b) The 12 pathways directly related to the immune system. RSGB: Renshen Guben oral liquid, KEGG: Kyoto Encyclopedia of Genes and GenomesMolecular docking verification
The potential key components and key targets were verified by molecular docking. The binding interaction between the ligand and the receptor is more stable when the binding energy is lower, thus leading to a greater possibility of action. The binding energy ≤ −5.0 kcal/mol is considered that the compound has good binding ability with the corresponding target.[39] The results showed that the affinity between the key components and the key targets of RSGB was < −5.0 kcal/mol, indicating that the predicted key components of RSGB and the key targets related to the mechanism of immune regulation had good binding activity. Thus, the prediction of this study was reliable. A total of 20 pairs of docking results were obtained [Table 1]. Detailed information about the interaction of the target compound with the docking simulation is shown in [Figure 5].
Figure 5: Visualization of partial docking results. TNF: Tumor necrosis factor
Table 1: Docking scores of the active components of Renshen Guben oral liquid with their potential targetsDrug-compound-target-pathway network
The drug-compound-target-pathway network was constructed by connecting drugs, key active components, key targets, and key pathways, as shown in [Figure 6]a. Some key targets were also enriched in the B cell signaling pathway and T cell signaling pathway. By exploring the key active components, targets, and signaling pathways, the mechanism of RSGB in regulating immunity was revealed by the network pharmacology method, as shown in [Figure 6]b.
Figure 6: (a) Drug-compound-target-pathway network. (b) Illustration of the important immunoregulatory processes involved in RSGB. RSGB: Renshen Guben oral liquid, TNF: Tumor necrosis factor, IL: InterleukinRenshen Guben oral liquid against diseases based on enhancing immunity
Potential targets of Renshen Guben oral liquid against diseases
Jvenn was used to intersect the targets of RSGB, immunity targets, and the targets of the three diseases. This resulted in 297, 292, and 270 potential targets of RSGB against MPS, PCOS, and CRF, respectively, as shown in [Figure 7]a, [Figure 7]d and [Figure 7]g.
Figure 7: Results of network pharmacological analysis of RSGB against diseases. Venn diagram of potential targets of RSGB against MPS (a), PCOS (d), and CRF (g). PPI network of potential targets for RSGB against MPS (b), PCOS (e), and CRF (h). KEGG analysis of potential targets of RSGB against MPS (c), PCOS (f), and CRF (i). RSGB: Renshen Guben oral liquid, MPS: Menopausal syndrome, PCOS: Polycystic ovary syndrome, CRF: Cancer-related fatigueProtein-protein interaction network of potential targets for Renshen Guben oral liquid against diseases
PPI networks of potential targets for RSGB therapy of MPS, PCOS, and CRF were constructed, as shown in [Figure 7]b, [Figure 7]e and [Figure 7]h. Among them, the PPI network of potential targets for RSGB in the treatment of MPS consists of 294 nodes (MBTD1, TNNC1, and AMY1A degree value were 0, so abandoned) and 5052 edges; the PPI network of potential targets for RSGB in the treatment of PCOS consists of 291 nodes (C3MBTL3 degree value was 0, so abandoned) and 4583 edges; the PPI network of potential targets for RSGB in the treatment of CRF consists of 270 nodes and 4518 edges. Among the three PPI networks, the targets with the first 10 degrees values both were AKT1, GAPDH, IL6, VEGFA, MAPK3, EGFR, TNF, SRC, MAPK1, and STAT3; and the eight targets of AKT1, IL6, VEGFA, EGFR, TNF, SRC, MAPK1, and STAT3 are also the key targets of RSGB immunoregulatory mechanism. This indicates that the process of RSGB against the three diseases is closely related to the mechanism of immune regulation.
Kyoto Encyclopedia of Genes and Genomes analysis
The DAVID database was used for the KEGG analysis of the potential targets of RSGB in the treatment of the three diseases. MPS, PCOS, and CRF were enriched in 114 and 120 pathways, respectively (P < 0.05 and FDR < 0.05). The KEGG pathway database was used to screen pathways directly related to the immune system. MPS, PCOS, and CRF were 10, 10, and 11 pathways, respectively, as shown in [Figure 7]c, [Figure 7]f and [Figure 7]i. It shows that RSGB may enhance immunity by regulating immune-related pathways, which may be beneficial for MPS, PCOS, and CRF patients. By exploring potential therapeutic targets and signaling pathways, the network pharmacology method reveals the key biological process of RSGB in the treatment of MPS, PCOS, and CRF, as shown in [Figure 8].
Figure 8: Illustration of the key biological processes involving potential targets of RSGB in the treatment of MPS (a), PCOS (b) and CRF (c). RSGB: Renshen Guben oral liquid, MPS: Menopausal syndrome, PCOS: Polycystic ovary syndrome, CRF: Cancer-related fatigue, TNF: Tumor necrosis factor Discussion In recent years, more and more attention has been paid to the regulatory effect of TCM on immune function.[40] By studying the regulatory effect of TCM on immune function, immune modulators with clinical application value may be developed, which can be used to prevent and treat tumor, infection, transplant rejection, and autoimmune diseases.[41],[42],[43] TCM in treating diseases from the overall view, dialectical treatment, reflects the idea of multicomponent, multitarget, and systematic regulation. Network pharmacology studies problems from the perspective of interconnection, which is consistent with the core idea of TCM. More and more researchers have applied network pharmacology to TCM research.[44],[45],[46] The combination of network pharmacology and TCM research has unique advantages and great potential for development.[47]
The drug-compound target network was constructed to analyze the interaction between components and targets. Combined with the degree of compounds in the network and related research reports, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Re, paeonol, (+)-catechin, quercetin, dehydroebruricoid, kaempferol, and arachidonate were deduced as the key active components of RSGB that play important roles in immune regulation. Ginsenoside Rg1 has immunoregulatory capacity, such as increasing the immune activity of T helper (Th) cells. Moreover, ginsenoside Rg1 can enhance the humoral and cellular responses induced by recombinant Toxoplasma gondii SAG1 antigen in mice.[21] Ginsenoside Rb1 regulates cytokine production in mouse macrophages, upregulates the phagocytic function of inactive macrophages, and promotes innate immunity against pathogen invasion.[48] Ginsenoside Re can promote the proliferation of human CD4+ T cells and reduce cell death.[49] The content of paeonol in RSGB was also high, and paeonol was found to promote phagocytosis of macrophages by confining high mobility group protein B1 on the nucleus.[50] Catechins have protective effects on humoral immunity and cellular immunity in rats.[51]
IL6 is a pleiotropic cytokine produced by stromal cells, hematopoietic cells, epithelial cells, and other cells. It has multiple validities and multiple functions in the immune system.[52] IL6 can stimulate the production of antibodies, promote the growth of T cells, and induce the development of T effector cells, which plays an essential role in the process of acquired immune response.[53] IL6 can induce activated B cells to differentiate into immunoglobulins,[54] and more importantly, IL6 can induce T cells to differentiate into functional lineages.[55],[56] TNF is one of the cytokines that can kill tumor cells directly but has no apparent toxicity to a normal cell. TNF is a regulatory cytokine that plays a crucial role in the signal transmission of proteins in the immune system.[57] It organizes the communication between immune cells and controls their many functions.[58] TNF can act directly on effector cells, promote the expression of MHC-antigens of T cells, boost the proliferation of thymocytes and T cells dependent on IL2, and promote the production of lymphokines such as IL2 and macrophage colony-stimulating factor.[59],[60],[61],[62] The combination of TNF and interferon-gamma can directly induce the permanent growth arrest of tumor cells, which may be the mechanism of biological prevention of malignant tumors.[63]
To further reveal the function of common targets of RSGB and immunity, ClueGO functional enrichment analysis and KEGG analysis were performed. Analysis of ClueGO enrichment results revealed that the common targets were mainly related to leukocyte differentiation, T cell activation, T cell promotion, and positive regulation of immune response. Analysis of KEGG enrichment results revealed that the pathways directly related to the immune system included the T cell receptor signaling pathway, B cell receptor signaling pathway, and so on. The active components of RSGB may regulate the immune response by regulating the above signaling pathways to enhance the immune function of the body. Notably, at least ten signaling pathways directly related to the immune system were enriched in the KEGG analysis of potential targets of RSGB against MPS, PCOS, and CRF. This suggests that RSGB can improve the immunity of patients through these signaling pathways to directly treat or assist in the treatment of disease.
MPS refers to a series of symptoms caused by the fluctuation or decrease of sex hormones before and after menopause. It mainly consists of autonomic nervous system dysfunction. MPS is accompanied by neuropsychological symptoms, which have also been referred to as the perimenopausal syndrome.[64] Studies have shown that the immune function of patients with MPS and normal perimenopausal women is attenuated, that is, in the process of the immune response, the number of cells (such as CD3+, CD4+) that increase the ability of immune response is decreased. In contrast, the number of cells (such as CD8+ cells) with a decreased ability of immune response is increased.[65] With the increasing age, the immune regulatory function of perimenopausal women shows an aging trend. Related studies also showed that the expression level of cytokines such as IL6 and TNF, which play an important role in immune regulation, is correlated with the decrease in hormone levels in patients with MPS; this suggests that there is immune activation in MPS, and the changes in IL6 and TNF-α levels can be used as a sensitive indicator of disease changes.[66] RSGB may promote the proliferation and differentiation of T cells by regulating the secretion of IL6, TNF, and other immunomodulatory substances, increasing the number of cell groups (such as CD3+ and CD4+) that can increase the immune responsiveness, and reducing the cell population (such as CD8+ cells) with lower immune responsiveness and regulating hormone levels in patients to improve patients' immune responsiveness and achieve the purpose of treatment.
PCOS is a common and highly heterogeneous endocrine disorder in women of childbearing age. It affects fertility in 8%–12% of women of childbearing age, and the abortion rate is three times that of normal women.[67] The etiology of PCOS is still not entirely clear, and the pathogenesis is complex and involves multiple systems and organs; currently, more and more scientists are paying attention to the etiology and pathogenesis of PCOS.[68],[69],[70] Since the initial discovery that PCOS patients are in a state of low-grade chronic inflammatory response,[71] it has been confirmed that a variety of proinflammatory markers and mediators are elevated in women with PCOS. This type of subclinical inflammation belongs to autoimmune inflammation and inflammation below the infectious level. It is mainly manifested in increased chronic inflammatory factors such as C-reactive protein, IL6, and TNF-α in patients with PCOS.[72],[73] It is speculated that chronic inflammation may cause changes in the immune status of patients with PCOS. Hormones and immune cells interact in PCOS; female immune status is closely related to the prevalence of PCOS.[74] RSGB may reduce the secretion of chronic inflammatory factors such as IL6, TNF, and other chronic inflammatory factors in patients, thereby regulating the pathological state of chronic inflammation in patients and treating diseases.
CRF is a common complication that affects the treatment and quality of life of cancer patients, and it is one of the problems that cause the pain of most cancer patients.[75] The incidence of CRF in cancer patients is up to 52%, which seriously affects the quality of life, follow-up treatment, and survival of patients.[76],[77] CRF is related to the type of tumors and treatment methods. However, the presence of tumors and the associated treatment lead to the decline of various functions of patients, including immune function. In recent years, research on regulating the level of cytokines to regulate the immune function of CRF patients and improve the degree of fatigue has become more extensive.[78],[79] Studies have found that TNF, IL6, IL2, and other cytokines can lead to CRF; downregulating the level of inflammatory factors in serum may be a possible mechanism for treating CRF.[80],[81],[82] Because IL6, TNF, and other cytokines can inhibit the production of human erythropoietin, reduce the hemoglobin content and oxygen-carrying concentration of the human body.[83] The body lacks sufficient oxygen for metabolism, so it can accumulate more lactic acid, leading to fatigue. It can also cause inflammation of the body, induce mental anxiety or depression, and further make the patient tired.[84],[85] RSGB can alleviate the clinical symptoms of CRF by regulating the secretion of cytokines such as IL6 and TNF.
ConclusionsThis study applied the network pharmacology method to analyze the immunomodulatory effect of RSGB in the human body. Moreover, it is considered that RSGB has the potential to become a candidate drug for immunomodulators, which provides direction for subsequent research on effective compounds and action targets of RSGB and also provides a theoretical basis for the clinical application of RSGB.
Financial support and sponsorship
This work was supported by the National Nature Science Foundation of China (No. 81673829).
Conflicts of interest
There are no conflicts of interest.
References
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