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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 8  |  Issue : 1  |  Page : 100-109

Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis


1 Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, China
2 Department of Anesthesiology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
3 Department of Veterinary Medicine, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China
4 Department of Pathology, School of Basic Medical Sciences, Henan University of Science and Technology, Henan Province, China

Date of Submission09-Sep-2020
Date of Acceptance03-Feb-2021
Date of Web Publication29-Jan-2022

Correspondence Address:
Dr. Gao-Feng Liang
School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, Henan Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/wjtcm.wjtcm_46_21

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  Abstract 


San Miao Wan (SMW) is a traditional Chinese medicine (composed of Cortex phellodendri, Rhizoma atractylodes, and Radix cyathulae) widely used in China to treat arthritis; however, its underlying mechanism remains unknown. We established the target gene library of SMW and performed gene ontology enrichment analysis of related target genes. The component-target protein-protein interaction (PPI) network of SMW and the disease-target PPI network of arthritis were merged to form a core PPI network. Finally, the anti-oxidative effect of SMW for treating arthritis was evaluated in a rat arthritis model induced by sodium urate. The results showed that R. atractylodes contained four active components with 68 target proteins, R. cyathulae contained two active components and 139 target proteins, and C. phellodendri contained eight active components and 275 target proteins. The target genes of R. cyathulae were highly related to the synthesis and metabolism of reactive oxygen species, while target genes of R. atractylodes and C. phellodendri were highly related to the circulatory system. The component-target PPI network of SMW and the disease-target PPI network of arthritis predominantly overlapped. In vivo, SMW effectively reduced knee swelling induced by sodium urate, decreased serum malondialdehyde levels, and increased serum superoxide dismutase levels. In conclusion, the therapeutic effects of SMW in arthritis are associated with its anti-oxidative properties.

Keywords: Anti-oxidation; arthritis; network pharmacology; San Miao Wan


How to cite this article:
Hao XQ, Kou YQ, Xie XJ, JW, Lv JB, Su J, Liu KX, Liang GF. Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis. World J Tradit Chin Med 2022;8:100-9

How to cite this URL:
Hao XQ, Kou YQ, Xie XJ, JW, Lv JB, Su J, Liu KX, Liang GF. Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis. World J Tradit Chin Med [serial online] 2022 [cited 2022 May 18];8:100-9. Available from: https://www.wjtcm.net/text.asp?2022/8/1/100/336833




  Introduction Top


San Miao Wan (SMW) is a traditional Chinese medicine (TCM) composed of Cortex phellodendri (120 g), Rhizoma atractylodes (180 g), and Radix cyathulae (60 g).[1] According to the Chinese Pharmacopeia 2015 and The Database of Ethno-medicines in the world (https://ethmed.toyama-wakan.net), C. phellodendri, the dry bark of Phellodendron chinense Schneid (TMPW No. 2378), is also known as Huangbo in Chinese and Obaku in Japanese. R. atractylodes is the dried rhizome of Atractylodes lancea (Thunb.) DC. or A. chinensis (DC.) Koidz. (TMPW No. 343) and is also known as Cangzhu in Chinese and Sojutsu in Japanese. R. cyathulae, the dried root of Cyathula officinalis Kuan (TMPW No. 4644), is also known as Chuanniuxi in Chinese and Goshitsu in Japanese. According to the theory and philosophy of TCM, the main functions of SMW are clearing heat, drying dampness, and tonifying the liver and kidney.[1],[2]

SMW has been used to treat arthritis for thousands of years, although its mechanism of action remains unknown (Wang et al., 2017). The clinical applications of TCM are based on methods, theories, and philosophies that are completely distinct from the tenets of Western medicine. As a unique system that follows classical Chinese philosophy, TCMs often contain a multitude of ingredients that interact with multiple proteins in vivo. Therefore, the mechanisms underlying the effects of TCMs are complicated and difficult to explain. Western medicine is generally based on the use of a single compound to target a specific disease. Thus, strategies that bridge the theories of TCM and Western medicine are urgently required.

Network pharmacology, a new discipline based on the characteristics of biological molecules, utilizes multiple authoritative databases to gain an initial understanding of the mechanisms of medicines and diseases.[3],[4] Analytical network pharmacology can help elucidate the systematic effects and interactions of a multitude of compounds contained in TCMs at the molecular, cellular, and tissue levels. Moreover, network pharmacology can help interpret TCM in terms of modern medicine to connect philosophies of TCM and Western medicine. For example, Li et al. used a published data-based systems pharmacology approach to analyze the network pharmacology of Huang-Lian-Jie-Du-Tang, a well-known traditional Chinese formula. The results indicated that the essence of “body fire” in TCM is associated with anti-inflammatory and anti-infective functions, implicating the phosphatidylinositol 3-kinase/protein kinase B (AKT), mitogen-activated protein kinase, vascular endothelial growth factor, and calcium signaling pathways as potential underlying mechanisms.[3],[4] Li et al. have identified the pharmacological mechanism of ShenQi FuZheng injection combined with docetaxel for lung cancer therapy.[3] Sidders et al. have coupled network pharmacology with phenotypic screening for drug discovery.[5] In addition to SMW, other known formulas in accordance with the number of herbs in the prescription include Si Miao Wan (containing four herbs) and Qi Miao Wan (containing seven herbs). Recently, a network pharmacology-based study of Si Miao Wan in gout treatment was reported in a Chinese journal.[6] The authors analyzed the network pharmacology of Si Miao Wan and verified the cellular mechanism. Reportedly, Si Miao Wan is a four-herb prescription, with one more herb (Semen coicis) than SMW.

In the present study, we used a network pharmacology approach to investigate the therapeutic mechanism of SMW in arthritis and verified the anti-oxidative mechanism in a rat model.


  Materials and Methods Top


Prediction of the anti-oxidative mechanism

Construction of a component-target network

The TCM Systems Pharmacology Database and Analysis Platform (TCMSP, http://lsp.nwu.edu.cn/tcmsp.php) was used to establish the target library for SMW. First, the chemical components of C. phellodendri, R. atractylodes, and R. cyathulae were searched in TCMSP, and their active components were screened according to the following parameters: oral bioavailability (OB), ≥30%; drug-likeness (DL), ≥0.18.[3] OB represents the percentage of an orally administered dose of the unchanged drug that enters the bloodstream. High OB indicates the potential of drug-like properties of a bioactive molecule to function as a therapeutic agent.[7] DL is a qualitative concept used in drug design to estimate the “drug-like” qualities of a compound; a DL value of 0.18 is used as a screening criterion for the DL of compounds in TCMs.[8] The identified target proteins were assigned to their respective gene names in UniProt (https://www.uniprot.org/). Cytoscape_3.2.1 software was used to construct the component-target networks of C. phellodendri, R. atractylodes, and R. cyathulae.

Creation of protein-protein interaction networks

The disease-target proteins of arthritis were predicted using the Therapeutic Targets Database (http://bidd.nus.edu.sg/BIDD-Databases/TTD/TTD.asp). In total, 157 target proteins were assigned to their respective gene names in UniProt (https://www.uniprot.org/). Using Cytoscape (version 3. 2. 1, Cytoscape Consortium, San Francisco, USA) and BisoGenet (Version 3.0.0, Center for Genetic Engineering and Biotechnology, Havana, Cuba), the protein-protein interactions (PPI) of 152 target genes of the active components and 157 disease-target genes were analyzed, and ingredient-target and disease-target PPI networks were created. The ingredient-target and disease-target networks were then combined to produce a merged network using the intersection method.

Gene ontology function enrichment

Gene ontology (GO) enrichment analysis of related target genes of R. cyathulae, R. atractylodes, and C. phellodendri was performed using Cytoscape_3.2.1 software and the ClueGO network plugin. The differences in target genes were then analyzed using Venny 2.1(http://bioinfogp.cnb.csic.es/tools/venny/index.html) and differences in GO functions among R. cyathulae, R. atractylodes, and C. phellodendri were identified.

Kyoto Encyclopedia of Genes and Genomes pathway analysis

Pathways associated with SMW were predicted and analyzed using the bioinformatics analysis tools for molecular mechanism of TCM (BATMAN-TCM) database (http://bionet.ncpsb.org/batman-tcm/), as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database (https://www.genome.jp/kegg/pathway.html).[9]

Verification of the anti-oxidative effect of San Miao Wan in a rat arthritis model

Preparation of the San Miao Wan soup

C. phellodendri (120 g), R. atractylodes (180 g), and R. cyathulae (60 g) were added to 500 mL water in an earthenware cooking pot and boiled for 1 h. The residue was removed, and the medicine soup was placed in a drying oven to concentrate the drug to a final volume of 25 mL.

Animal model

Thirty Sprague Dawley (350–380 g) rats were purchased from Animal Center of Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China). Thirty Sprague Dawley (350–380 g) rats were divided into three groups (10 rats per group): the control group (injected with 50 μL 0.9% saline into the right foreleg knee joint); the S-urate group (injected with 50 μL 5% sodium urate [MedChemExpress, MCE; dissolved in ethanol] into the right foreleg knee joint); the SMW group (1.5 mL SMW soup administered orally by gavage daily for five days before injection with 5% sodium urate into the right foreleg knee joint). The present study was conducted in accordance with the principles outlined in the National Institutes of Health Guide for the Care and Use of Laboratory Animals (http://grants1.nih.gov/grants/olaw/) and was approved by the local animal ethics committee of Henan University of Science and Technology (No.370726210100370226).

Measurement of circumference and diameter of knee joints

Following anesthetization of rats with pentobarbital sodium (45 mg/kg), edema was evaluated at 1, 2, 3, and 4 h after the injection by measuring the circumference and diameter of the knee joints using a Vernier caliper.

Measurement of serum malondialdehyde levels

Blood samples were collected from the abdominal vein. After standing for 30 min at room temperature, the blood samples were centrifuged at 3,000 rpm for 10 min. The serum was collected and stored at −20°C. Serum malondialdehyde (MDA) levels were measured using a lipid oxidation assay kit (Beyotime Biotechnology Co. Ltd., Shanghai, China) according to the manufacturer's instructions. In this assay, the MDA measurement is based on the formation of a red product after the reaction between MDA and glucosinolate and barbituric acid. The absorbance of each well in microplates was measured at 532 nm using a SpectraMax M5 microplate reader (SpectraMax M5, CA, USA).

Measurement of serum superoxide dismutase

Blood superoxide dismutase (SOD) was measured using Total SOD Assay Kit with WST-8 (Beyotime Biotechnology Co. Ltd.) according to the manufacturer's instructions. SOD catalyzes the disproportionation of superoxide anions to produce hydrogen peroxide (H2O2) and oxygen (O2). The absorbance of each well in microplates was measured at 450 nm using a SpectraMax M5 microplate reader (SpectraMax M5, CA, USA).

Statistical analysis

Data are presented as means ± standard deviation. One-way ANOVA was used to assess statistical significance among groups. All analyses were performed using GraphPad Prism (version 6.0; GraphPad Software, Inc. CA, USA). Statistical significance was set at P < 0.05.


  Results Top


Screening of components and construction of the component-target network of Cortex phellodendri, Rhizoma atractylodes, and Radix cyathulae

The components of C. phellodendri, R. atractylodes, and R. cyathulae were screened based on the OB (≥30%) and DL (≥0.18) values. For C. phellodendri, we identified eight active components (beta-sitosterol, stigmasterol, magnograndiolide, palmatine, fumarine, isocorypalmine, berberine, and coptisine), along with 275 target proteins. For R. atractylodes, we identified four active components (beta-daucosterol, wogonin, NSC63551, and beta-sitosterol 3-O-glucoside) and 68 target proteins. For R. cyathulae, we identified two active components (quercetin and beta-sitosterol) and 138 target proteins. The components and component-target networks of the three natural herbs are shown in [Table 1] and [Figure 1].
Table 1: The screened main components of San Miao Wan

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Figure 1: Component-target network of Cortex phellodendri (a), Rhizoma Atractylodes (b) and Radix Cyathulae (c)

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Creation of drug-target and disease-target protein-protein interaction networks

We then created drug-target and disease-target PPI networks for SMW and arthritis, respectively, consisting of 152 target proteins of the active components in SMW and 157 target proteins related to arthritis [Figure 2]a and [Figure 2]b. The merged PPI network [Figure 2]c obtained by combining the drug-target and disease-target PPI networks largely overlapped. The core network [Figure 2]d was isolated from the merged network.
Figure 2: Drug-target protein-protein interaction network of San Miao Wan (a), disease-target protein-protein interaction network of arthritis (b), merged network of the drug-target protein-protein interaction network of San Miao Wan and the disease-target protein-protein interaction network of arthritis. The centrally located part (shown in yellow) of the merged network contains the core network with the important nodes and the core protein-protein interaction network of the merged network of drug-target protein-protein interaction network of San Miao Wan and the disease-target protein-protein interaction network of arthritis. Based on the concept that the quantitative 'degree' of the property of a node refers to the number of edges linked to it, suggesting the importance of that node in the network, the important nodes were identified and their core network was isolated (Ren et al., 2019)

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Gene ontology function analysis

Gene ontology function analysis of Radix cyathulae, Rhizoma atractylodes, and Cortex phellodendri

GO function analysis revealed that the target genes of R. cyathulae were highly related to the synthesis and metabolism of reactive oxygen species (ROS), response to toxic substances, cellular response to organic cyclic compounds, and blood circulation [Figure 3]a. The target genes of R. atractylodes were highly related to the circulatory system, as well as phospholipase C-activating G-protein coupled receptors (PLC-GPCRs) [Figure 3]b. The target genes of C. phellodendri were highly related to the circulatory system [Figure 3]d.
Figure 3: Enrichment of target genes in Radix cyathulae (P ≤ 0.01) (a), Rhizoma atractylodes (P ≤ 0.05) (b), Cortex phellodendri (P ≤ 0.05) (c) and Comparison of the numbers of genes targeted by Rhizoma atractylodes, Radix cyathulae and Cortex phellodendri (d)

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Comparison of target genes and gene ontology functions of Radix cyathulae, Rhizoma atractylodes, and Cortex phellodendri

R. cyathulae, R. atractylodes, and C. phellodendri shared 39 target genes [Figure 3]d. Most of these genes were found to be involved in PLC-GPCRs and regulation of blood pressure and blood vessel diameter [Figure 4]a, suggesting that these three herbs improve blood circulation, oxygenation, and CO2 elimination at inflammatory sites.
Figure 4: Enrichment of the same 39 genes in Rhizoma atractylodes, Cortex phellodendri and Radix cyathulae (a), the target genes in Radix cyathulae that were not the same as those enriched in Rhizoma Atractylodes (P ≤ 0.05) (b), quercetin target genes in Radix cyathulae (P ≤ 0.01) (c), beta-sitosterol target genes in Radix cyathulae (P ≤ 0.01) (d), Stigmasterol target genes in Cortex phellodendri (P ≤ 0.05) (e)

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Only six target genes in R. atractylodes differed from those in R. cyathulae [Figure 3]c. Therefore, we compared the target genes of R. cyathulae with those of R. atractylodes. Most of the differentially expressed genes were related to ROS synthesis and metabolism and the cellular response to cadmium ions [Figure 4]b.

R. atractylodes and R. cyathulae shared 44 target genes associated mainly with ROS metabolism, PLC-GPCRs, and nitric oxide biosynthesis. C. phellodendri and R. cyathulae shared 56 target genes that were highly related to PLC-GPCRs. Most target genes in R. atractylodes were identical to those in R. cyathulae and C. phellodendri (data not shown).

Gene ontology function of the active components in Radix cyathulae and Cortex phellodendri

Quercetin and beta-sitosterol are the two active components identified in R. cyathulae, and stigmasterol is the active component present in C. phellodendri. Enrichment of genes targeted by quercetin in R. cyathulae showed that quercetin primarily functions in processes such as the metabolism and regulation of ROS and superoxide metabolism [Figure 4]c. The other active compound in R. cyathulae, beta-sitosterol, functions mainly in the PLC-GPCR signaling pathway [Figure 4]d. These observations suggested that quercetin plays a crucial role in the function of R. cyathulae. Enrichment of target genes of stigmasterol in C. phellodendri revealed that stigmasterol acts mainly on regulating blood pressure [Figure 4]e. Berberine positively regulates cardiac muscle tissue development, while isocorypalmine also acts on blood pressure (figure not shown).

Kyoto Encyclopedia of Genes and Genomes pathway analysis

Among pathways involved in the functions of SMW, nuclear factor-kappa B (NF-κB) [Figure 5]a, tumor necrosis factor (TNF)[Figure 5]b and chemokine and chemokine [Figure 5]c signaling pathways are closely related to inflammation and oxidation. Overall, 14 genes were related to the TNF signaling pathway, 8 were related to the NF-κB signaling pathway, and 19 to the chemokine signaling pathway [Table 2]. In the chemokine signaling pathway [Figure 5]c, ROS are produced via the DAG-PKC-P47phox pathway (Zhang, et al., 2014). Notably, 26 genes were associated with cardiac muscle contraction, 36 were associated with adrenergic signaling in cardiomyocytes, 77 were associated with the calcium signaling pathway, 36 genes were related to dopaminergic synapse signaling, and 106 were associated with neuroactive ligand-receptor interactions.
Figure 5: Nuclear factor-kappa B signaling pathway (a), tumor necrosis factor signaling pathway (b) and chemokine signaling pathway (c)

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Table 2: Genes involved in the chemokine, nuclear factor.kappa B and tumor necrosis factor signaling pathways

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Verification of the anti-oxidative effect of San Miao Wan in a rat arthritis model

GO enrichment analysis revealed that the target genes of R. cyathulae were highly associated with ROS biosynthesis, positive regulation of ROS metabolism, and removal of superoxide radicals. Furthermore, GO enrichment analysis of SMW in the BATMAN database showed that 184 target genes of SMW were associated with the oxidoreductive activity. Therefore, our findings confirmed the anti-oxidative effect of SMW in a rat model of arthritis.

Knee joint circumference and diameter

The knee joint circumference in the S-urate group was larger than that in control and SMW groups at 2 and 4 h after the sodium urate injection [Figure 6]a and [Figure 6]b.
Figure 6: Effect of San Miao Wan on rat arthritis induced by sodium urate. (a) Effect of San Miao Wan on knee circumference 2 h after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA), (b) Effect of San Miao Wan on knee circumference 4 h after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA), (c) Effect of San Miao Wan on knee diameter 2 h after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA), (d) Effect of San Miao Wan on knee diameter 4 h after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA), (e) San Miao Wan decreased serum MDA levels after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA), (f) San Miao Wan increased serum SOD activity after injection of sodium urate. Data represent the mean ± standard deviation (n = 8 per group). **P < 0.01 versus Control group and S-Urate+ San Miao Wan group (one-way ANOVA)

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The diameter of the knee joints in the S-urate group was greater than that in control and SMW groups at 2 and 4 h after the sodium urate injection [Figure 6]c and [Figure 6]d.

Serum malondialdehyde and superoxide dismutase levels

Serum MDA levels in the S-urate group were higher than those in the control and SMW groups, while serum SOD levels were found to be lower [Figure 6]e and [Figure 6]f, respectively].


  Discussion Top


SMW, a popular prescription for treating arthritis, has been used for thousands of years in China. However, little is known regarding its underlying mechanism of action. A previous study has reported that SMW is a potential anti-inflammatory agent that can be considered an alternative to non-steroidal anti-inflammatory drugs.[10] Si Miao Wan is another prescription that contains an additional herb when compared with SMW. Other similar prescriptions are also available, such as Er Miao Wan (containing two herbs), Wu Miao Wan (containing five herbs), and Qi Miao Wan (containing seven herbs).

Prediction and verification

In the present study, we first analyzed the network pharmacology of SMW by constructing component-target networks and GO enrichment analysis. We then constructed a drug-target PPI network for SMW and the disease-target PPI network of arthritis, which were merged to generate the core PPI network. We observed that the targets of R. cyathulae, a component of SMW, are highly related to ROS, including quercetin, identified in R. cyathulae. Therefore, we speculate that the therapeutic mechanism of SMW in arthritis involves anti-oxidative effects, attributed mainly to quercetin in R. cyathulae. C. phellodendri also demonstrates an effect, as the GO enrichment analysis revealed that C. phellodendri also mediates anti-oxidative effects. The anti-oxidative effects of SMW were verified in vivo using a rat model of arthritis. Oxidative status is mainly characterized by increased lipid peroxidation (reflected by MDA production) and decreased levels of antioxidant enzymes, such as SOD. The elevated SOD levels and attenuated MDA accumulation, as well as knee edema, indicated the anti-oxidative effects of SMW in a rat arthritis model.[11],[12]

Radix cyathulae

R. cyathulae is traditionally used as a wind-damp-dispelling and blood-stasis-removing medicinal agent, according to Chinese philosophy. It was also described as a medicine that could tonify the liver and kidney, strengthen bones and muscles, promote diuresis, and relieve stranguria. In proprietary Chinese medicine, R. cyathulae decoction is employed to treat various orthopedic, gynecological, and urological diseases.[13] Studies have shown that the water-soluble extracts of R. cyathulae significantly reduce MDA levels in liver tissues and increase serum SOD levels. Furthermore, R. cyathulae alleviates joint edema in rats with acute ventilated arthritis via a mechanism that may involve downregulating the expression of NF-κB P65 and inhibiting NF-κB activity.[13] In the present study, we observed that target genes of R. cyathulae are related to ROS biosynthesis and are associated with processes that respond to toxic substances, blood circulation, positive regulation of smooth muscle cell proliferation, and regulation of the developmental growth. These functions are consistent with the results of the KEGG pathway analysis of SMW, in which 26 genes were found to be related to cardiac muscle contraction, 36 genes were related to adrenergic signaling in cardiomyocytes, 77 genes were related to the calcium signaling pathway, and 36 genes were related to dopaminergic synapse signaling. To a certain degree, these data might explain the traditional role of R. cyathulae in dispelling wind and eliminating dampness, removing blood stasis, strengthening bones and muscles, and tonifying the liver and kidney.

Rhizoma atractylodes

According to the theory of TCM, the spleen is involved in food digestion, nutrient absorption, and elimination of excessive water. R. atractylodes invigorates the spleen and removes dampness.[3] The network pharmacology analysis in the study revealed that target genes of R. atractylodes are mainly associated with aspects of the cardiovascular system, including regulating vascular processes and blood vessel diameter. Furthermore, several other target genes are involved in developing striated muscle tissue and smooth muscle contraction. These results, to some extent, may explain the dampness-removing function of R. atractylodes and provide insights into the mechanism via which this component activates the spleen. Studies have shown that R. atractylodes also possesses anti-inflammatory effects. For example, Ishii et al. have revealed that R. atractylodes decreases the production of prostaglandin E2 and nitric oxide (NO) (Ishii et al. and Hossen et al. have reported that an ethanol extract of R. atractylodes inhibits Akt/NF-κB signaling.[14],[15] In the present study, we observed that numerous target genes of R. atractylodes were related to PLC-GPCRs. According to the KEGG pathway analysis, three pathways, including inflammatory mediator regulation of transient receptor potential channels, human cytomegalovirus infection, and the cAMP signaling pathway, are associated with PLC-GPCRs, thus providing further evidence of the anti-inflammatory effects of R. atractylodes.

Cortex phellodendri

According to the scientific database of China Plant Species and Chinese Pharmacopeia (2015 edition), there are two main species of C. phellodendri: P. amurense Rupr or “Guan Huang bai” in Chinese, and P. chinense Schneid or “Chuan Huang bai” in Chinese. C. phellodendri is a classical TCM used to decrease kidney fire and reduce hot flashes and night sweats (Liu, et al., 2013). In TCM, the essence of fire is related to inflammation and infection.[3] C. phellodendri was found to share 56 target genes with R. cyathulae, all of which are highly related to PLC-GPCRs, suggesting the anti-inflammatory effects of C. phellodendri and R. cyathulae. Lipopolysaccharides (LPS), an important component of the outer wall of Gram-negative bacteria, are highly proinflammatory molecules.[3],[16] Studies have shown that an extract of P. amurense Rupr. efficiently regulates LPS-induced release of NO and inducible nitric oxide synthase production in microglia while attenuating the LPS-stimulated release of TNF- a and interleukin-1 b.[17] Furthermore, the targets of C. phellodendri were also shown to be related to blood circulation, monoamine transport, smooth muscle contraction, and blood pressure regulation.

Kyoto Encyclopedia of Genes and Genomes pathway

In the present study, the KEGG pathway analysis provided evidence supporting the anti-inflammatory mechanism of SMW in treating arthritis, which also explains the effects of dampness removal and liver and kidney invasion according to TCM philosophy.


  Conclusion Top


We analyzed the network pharmacology of SMW and confirmed its anti-oxidative effects in treating arthritis. This information will help guide the general clinical practice. Moreover, we compared the target genes and functions of R. cyathulae, R. atractylodes, and C. phellodendri and analyzed the functions of some active components. Our study also highlights the value of network pharmacology as an approach to elucidate molecular mechanisms of herbal medicine, creating a bridge between TCM and Western medicine. Furthermore, our study represents the basis of further investigations that will improve our understanding of the medicinal theory and philosophy of TCM.

Acknowledgments

Nil.

Financial support and sponsorship

This work was supported by the Henan Natural Science Foundation (No. 182300410370) and the Student Research Training Program (No. 2018299).

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2]



 

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