Skip to main content
Download PDF

Network pharmacology combined with molecular docking to explore the potential mechanisms for the antioxidant activity of Rheum tanguticum seeds

BMC Complementary Medicine and Therapies volume 22, Article number: 121 (2022) Cite this article

Abstract

Background

Rheum tanguticum (R. tanguticum) is an edible and medicinal plant that exhibits high antioxidant activity. The purpose of the present study was to investigate the bioactive components of its seeds and the potential mechanisms of antioxidant activity to provide a foundation for further developmental work on R. tanguticum seeds as a functional food.

Methods

In this study, the antioxidant activities of R. tanguticum seeds were measured using DPPH, ABTS and FRAP assays. LC-Q-TOF/MS was used to identify the active compounds in the seeds, and Swiss Target Prediction was used to identify their potential targets. The DisGENET, DrugBank, OMIM and GeneCard databases were used to search for antioxidant-related targets.

Results

The component–target–pathway network was constructed and included 5 compounds and 9 target genes. The hub genes included ESR1, APP, MAPK8, HSP90AA1, AKT1, MMP2, PTGS2, TGFB1 and JUN. The antioxidant activity signaling pathways of the compounds for the treatment of diseases were the cancer signaling pathway, estrogen signaling pathway, colorectal cancer signaling pathway, MAPK signaling pathway, etc. Molecular docking revealed that the compounds in R. tanguticum seeds could inhibit potential targets (AKT1, ESR1 and PTGS2).

Conclusion

Molecular docking studies revealed that the binding energy score between liriodenine and PTGS2 was the highest (8.16), followed by that of chrysophanol (7.10). This result supports the potential for PTGS2-targeted drug screening and design.

Peer Review reports

Background

Antioxidation is the process of inhibiting the oxidation reaction caused by reactive oxygen species (ROS) [1]. ROS are reactive molecules derived from oxygen and include superoxide anions (O2−), hydrogen peroxide (H2O2) and hydroxyl radicals (OH−) [2]. ROS are produced mainly in the mitochondria as a byproduct of biochemical reactions [3]. Many chronic diseases, including cancer, Alzheimer’s disease and diabetes, are thought to be linked to ROS imbalance [4]. The effects of antioxidants are exerted via pathways of cell growth, apoptosis and differentiation and help to prevent and protect against diseases [5]. Research has increasingly suggested that antioxidants are biologically essential to combat ROS and that insufficient levels of antioxidants in the body can be complemented by food [6, 7]. Hence, research on antioxidants in food, especially those in plants, is of much interest [8, 9].

For thousands of years, traditional Chinese medicine (TCM) has been used to prevent and treat diseases by medications with multi-ingredient, multitarget and synergetic benefits [10]. A previous study suggested that components in Fructus schisandrae may act on different targets and have great potential in the treatment of various diseases by exerting antioxidant activity [1]. The potential molecular mechanisms of lychee seeds as anti-inflammatory and antioxidant agents have also been explored [11]. In a study of Trigonella foenum-graecum L. seeds, various compounds were found to be useful in reducing the lipid levels of blood. These compounds work on the insulin signaling pathway and have antioxidant potential [12]. Muzaffer Silinsin et al. studied the antioxidant capacity of Inula graveolens (L.) Desf by UHPLC–MS/MS and demonstrated that the significant antioxidant capacity of the plant might be related to the high abundance of phenolic compounds [13]. In a study of Satureja boissieri, the results showed that its flavonoid and phenolic contents were good natural sources for use in the food industry and pharmacological processes [14]. Therefore, TCM medications may increasingly be used as antioxidants as the modern pharmacological understanding of their mechanisms progresses.

Rheum tanguticum Maxim. ex Balf. (R. tanguticum), a perennial plant of the genus Rheum L. from the Polygonaceae family, is a well-known Chinese herbal medicine [15]. The roots have been used as folk medicine for thousands of years in many countries, especially China, Korea and Japan [16]. The stems have high medicinal value and are low in calories. They are popular worldwide as a food to aid weight loss. It is recorded in the Medical Canon in Four Sections (Si Bu Yi Dian) that the stem, when the stem bark had been peeled off, was traditionally eaten in the Tibetan diet. The seeds of R. tanguticum are regarded as a byproduct, and only small amounts of the seeds are used for breeding, while the rest are discarded as waste. Phytochemical research has shown that rhubarb seeds contain 17 amino acids, with a total amino acid content as high as 18.43% [17]. The seeds are also rich in polysaccharides and proteins [18]. Polysaccharides from plants are characterized as natural antioxidants with excellent antioxidant activity [19]. Emodin and rhein, derived from rhubarb seeds, have been reported to possess a wide range of antioxidant, antibacterial, anti-inflammatory and antimicrobial biological activities [20, 21]. Compared with synthetic antioxidants, natural antioxidants from medicinal plants are more desirable in terms of health. Therefore, seeds can be recommended as a novel natural source of antioxidants [22]. Given the antioxidant potential of R. tanguticum seed extract, it is important to evaluate its antioxidant activity, and further research on its chemical constituents is warranted. Several methods, including assays based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), are commonly used for the determination of antioxidant activity [23]. For example, the antioxidant properties of Inula discoidea were determined by the ABTS, DPPH, and FRAP methods [24]. To the best of our knowledge, there are no previous studies on the antioxidant activities of R. tanguticum seed extracts.

The complexity of TCM ingredients makes it difficult to disentangle the molecular mechanisms of action on diseases. As a cross-discipline combining bioinformatics, computer simulation and molecular network data, network pharmacology is an emerging tool for TCM data mining [25, 26]. A component–target–pathway–disease network can be established to systematically explore the underlying mechanisms of TCM in treating disease. Molecular docking is widely used in computer-assisted drug design technology to estimate the major binding modes of small molecules with the 3D structure of the target protein [27]. Both techniques have been successfully applied in TCM to identify compounds with potential efficacy in treating diseases [28, 29]. Attempts toward this direction have already been reported for R. tanguticum, focusing on multiple active ingredients aimed at multiple targets [30]. However, systematically understanding how multiple therapeutic targets work together to exert antioxidant effects still needs further investigation.

Our study aimed to verify whether R. tanguticum seeds have antioxidant activity and to explain how the major components related to the antioxidant mechanisms work. Here, we measured the antioxidant capacity (DPPH, ABTS and FRAP) of R. tanguticum seeds and identified the bioactive metabolites in the seed extract through liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Furthermore, the component–target–pathway network was investigated using network pharmacology analysis to explore the potential molecular mechanisms of the antioxidants. Molecular docking studies for the identified compounds were then conducted to evaluate their therapeutic potential and facilitate the design of candidates for treating oxidative diseases.

Materials and methods

Plant materials and sample preparation

The seeds were obtained from R. tanguticum plants at the Haidong Agricultural Experiment Station (Qinghai, China). Authentication was provided by Prof. Guoying Zhou of the Northwest Plateau Institute of Biology. The seeds were ground into powder using a grinder, packed into sealed polyethylene bags and kept at 4 °C for further use.

The powder was precisely weighed to 1 g, and 20 mL distilled water was added to the tubes. Following sonication (30 °C, 90 min, 350 w), the samples were centrifuged at 4000 r/min for 10 min, and the supernatant was collected. The resulting residue was added to 5 mL distilled water and centrifuged again under the same conditions. The supernatants were combined, and the volume was made to 50 mL with distilled water. The resultant reagent was used for subsequent experiments.

Chemicals and reagents

Total antioxidant capacity assay kits for ABTS and FRAP were acquired from the Nanjing Jian Cheng Bioengineering Institute (Nanjing, China). All other chemicals, including phosphoric acid and ethanol, were of analytical grade and provided by Chengdu Cologne Chemical Co., Ltd. (Chengdu, China).

Determination of antioxidant capacity

DPPH free radical scavenging activity assay

The free radical scavenging capacity of R. tanguticum seeds was determined using DPPH following a modified method [31]. Sample solution (2 mL) was added to 0.2 mmol/L DPPH in ethanol solution (2 mL) and mixed. After reacting in the dark for 30 min, the absorption values at 517 nm were measured using a UV spectrophotometer (756PC, Shanghai, China). The DPPH radical scavenging ability was calculated according to Eq. (1):

$$\mathrm{DPPH}\ \mathrm{scavenging}\ \mathrm{activity}\%=\left(\ 1-\frac{\mathrm{A}\mathrm{i}-\mathrm{Aj}}{\mathrm{A}0}\ \right)\times 100$$
(1)

where Ai is the absorbance of the sample and A0 is the absorbance of the blank, in which the samples containing R. tanguticum seed extracts were replaced by anhydrous ethanol. Moreover, in the control group, DPPH was replaced by 2 mL anhydrous ethanol (Aj). Vitamin C (VC) served as a positive control. Each experiment was performed in triplicate.

ABTS scavenging activity assay

Blue ABTS+ is inhibited by antioxidants, and the total antioxidant capacity of a sample can be calculated by reading the absorbance [32]. For the ABTS+ radical scavenging assay, the amount of ABTS was measured using an assay kit (A015–2-1). The kit included concentrated detection buffer, ABTS solution, substrate solution and Trolox solution. The ABTS working solution was made by mixing the first three reagents at a 76:5:4 ratio. Trolox is a water-soluble vitamin E analog and serves as an antioxidant standard [33]. Trolox (10 mM) was diluted to concentrations of 0.1, 0.2, 0.4, 0.8 and 1.0 mM with distilled water. The test sample solutions (10 μL) were added to 20 μL of substrate solution. Then, 170 μL of ABTS working solution was added to each well, and the absorbance was determined at 405 nm after reacting at room temperature for 6 min. Distilled water was used as a blank control. OD values were detected using an Epoch2 Microplate Spectrophotometer (BioTek, USA). Concentrations were plotted on the y-axis, while OD values were plotted on the x-axis. The ABTS concentration in each sample was calculated based on the standard curve (y = −0.928x + 1.0226, R2 = 0.9975).

Ferric ion reducing antioxidant power (FRAP) assay

The FRAP assay was carried out using a Total Antioxidant Capacity Assay Kit (A015–3-1) [34]. The FRAP working solution was prepared by mixing detection buffer, matrix fluid and substrate solution according to a 10:1:1 ratio. Meanwhile, 27.8 mg of FeSO4·7H2O was dissolved in 1 mL of distilled water. Subsequently, the standard solutions were serially diluted to concentrations of 0.15, 0.3, 0.6, 0.9, 1.2 and 1.5 mM. Sample solution (5 μL) was added to 180 μL of FRAP working solution in 96-well plates. The reaction mixtures were incubated for 3–5 min at 37 °C. The absorbance was then measured at 593 nm with an Epoch2 Microplate Spectrophotometer (BioTek, USA). Each sample was measured in triplicate, and the average value was calculated. A standard curve with the OD values on the y-axis and the concentration on the x-axis was plotted and yielded the following equation: y = 3.5851x − 0.6010, R2 = 0.9979. The absorbance of the sample was inserted into the equation to obtain the FRAP concentration.

LC-Q-TOF/MS analysis

The seeds were analyzed qualitatively using LC-Q-TOF/MS. This part of the study was completed by Shanghai Weipu Chemical Technology Company in China.

Network pharmacology analysis

Target collection and potential target prediction

The targets of the active compounds were predicted using Swiss Target Prediction (http://www.swisstargetprediction.ch/) [35].

GeneCards (https://www.genecards.org/) [36], DrugBank (https://www.drugbank.ca/) [37], DisGeNet (https://www.disgenet.org/) [38] and OMIM (http://www.omim.org/) [39] were used to select genes with ‘oxidative’ as the keyword. Venn diagrams (http://www.bioinformatics.com.cn/) were used to determine the intersection targets between compounds and disease.

Protein–protein interaction (PPI) and component–target–pathway network

Following intersection, targets were screened, and their PPI network diagram was established using STRING (https://string-db.org/) [40]). The component–target–pathway network was visualized using Cytoscape software (version 3.7.2).

GO enrichment and KEGG analysis

DAVID (https://david.abcc.ncifcrf.gov/) was used to perform GO function and KEGG (www.kegg.jp/kegg/kegg1.html) pathway enrichment analyses with Homo sapiens as the selected species [41,42,43,44]. This was visualized using the Weishengxin online tool (http://www.bioinformatics.com.cn/) [45]. The threshold level for all GO enrichment and pathway analyses was set as p < 0.05. The top-ranked pathways were integrated and plotted as the final pathway map.

Molecular docking

The 2D structures of major active ingredients were retrieved from the PubChem (https://pubchem.ncbi.nlm.nih.gov/) database and saved as PDB files for further analysis [46]. The structure of the target protein (PDB format) was downloaded from the PDB database (https://www.rcsb.org/) [47]. Protein structures were hydrogenated, and water was removed using PyMOL (v2.1.0). The plugin PyVOL was used to explore and visualize binding pockets. Each ligand or small molecule was hydrogenated with AutoDock version 4.2.6. The size of the box was chosen to cover the potential active pocket. Molecular docking simulations were performed using Autogrid.

Data analysis

Data are expressed as the mean ± SE. All of the extractions and analyses were performed in triplicate.

Results

Antioxidant capacity of R. tanguticum seed extracts

As shown in Fig. 1, as the seed extract and VC concentration increased, the DPPH free radical scavenging rate increased accordingly. When the concentration of VC in the positive control reached 60 mg/L, VC had the highest scavenging rate of the DPPH free radical, which was 95.8%, while the scavenging rate of R. tanguticum seed extracts plateaued at approximately 85%. However, the IC50 values were 12.31 and 15.06 mg/L, respectively. A higher rate of DPPH free radicals was obtained for R. tanguticum seed extracts in the concentration range of 12 ~ 20 mg/L compared to VC.

Fig. 1
figure 1

DPPH scavenging activity of Rheum tanguticum seed extracts

Full size image

For the ABTS assay, Trolox was used as the standard, and the results were expressed as Trolox equivalents. For the FRAP assay, FeSO4·7H2O was used as the standard, and the results were expressed as FeSO4·7H2O equivalents. In our results, the ABTS radical cation scavenging ability and FRAP value of R. tanguticum seed extracts were 0.78 and 1.22 mmol/L, respectively (Table 1).

Table 1 Results of three antioxidant assays (DPPH radical scavenging activity, Vitamin C expressed in IC50; ABTS expressed in Trolox equivalent; FRAP expressed in FeSO4·7H2O equivalent)
Full size table

Identification of the metabolites in R. tanguticum seed extracts

The metabolites were extracted and analyzed using LC-Q-TOF/MS in both positive and negative ion modes. As shown in Table 2, 24 substances were identified, including kaempferol, propionic acid, emodin, chrysophanol and quercetin.

Table 2 Twenty-four compounds identified in Rheum tanguticum seeds
Full size table

Network pharmacology analysis

Potential targets of the main active compounds and antioxidants

Among the 24 ingredients in the seed extracts, 15 were selected by ADME (absorption, distribution, metabolism and excretion) and Lipinski’s rule of five screenings [48]. According to Swiss Target Prediction, 12 of the ingredients had a combined total of 261 potential targets with a probability larger than 0. Using ‘oxidative’ as a keyword, the related genes were selected from the disease gene databases (OMIM, GeneCards, DrugBank, DisGeNet). The results were pooled, and duplicates were deleted, leaving 1040 records to screen. Venn diagrams showed 43 intersections of oxidative-related and active ingredient targets (Fig. 2A). The intersection targets and corresponding compounds were imported into Cytoscape to draw a compound–target network diagram (Fig. 2B). This network contained 49 nodes linked via 80 edges, which revealed the synergistic multicomponent and multitargeted effects of R. tanguticum seeds contributing to their antioxidant activities.

Fig. 2
figure 2

Venn diagram of active compound targets of R. tanguticum seeds and antioxidant targets (A) and interaction network between active components and intersection targets in R. tanguticum seeds (B)

Full size image

PPI network of the targets

To identify the hub genes in key modules, PPI network analysis was performed using the STRING database, and results with a combined score of ≥0.4 were selected (Fig. 3). The specific information is shown in Table 3. The top 10 hub genes were selected from the PPI network using the MCC algorithm and CytoHubba plugin. As shown in Fig. 4, the top three functional clusters of modules were selected (module 1, MCODE score = 5.8; module 2, MCODE score = 4.2; module 3, MCODE score = 3.0). Nine hub genes were identified by the intersection targets of MCC and MCODE (ESR1, APP, MAPK8, HSP90AA1, AKT1, MMP2, PTGS2, TGFB1 and JUN). The corresponding five metabolites were emodin, quercetin, liriodenine, chrysophanol and kaempferol. The results showed that a wide variety of substances could be involved in the antioxidant effects, such as receptors (vasopressin V2 receptor, estrogen receptor and others), proteins (microtubule-associated protein tau), hormones (transthyretin) and enzymes (steryl-sulfatase, telomerase reverse transcriptase, angiotensin-converting enzyme and others).

Fig. 3
figure 3

Protein–protein interaction (PPI) network of R. tanguticum seeds as a target for antioxidant treatment

Full size image
Table 3 Intersection target prediction between active components and disease
Full size table
Fig. 4
figure 4

Modules in the PPI network of RTS for antioxidant treatment

Full size image

Gene Ontology (GO) and KEGG pathway analyses

The DAVID 6.8 database was used for GO analysis and KEGG pathway enrichment of the nine key targets. Through GO analysis, a total of 70 GO items with p < 0.05 were obtained, including 53 biological process entries, 10 cell component entries and 7 molecular function entries. As shown in Fig. 5, the top 10 terms were arranged in ascending order of p values. The biological processes mainly included positive regulation of nitric oxide biosynthetic process, cellular response to mechanical stimulus and positive regulation of fibroblast proliferation. The cellular components that were enriched predominantly included the nucleus, extracellular matrix, protein complex and plasma membrane. The top molecular functions primarily included enzyme binding, nitric oxide synthase regulator activity, identical protein binding and protein homodimerization activity. Next, KEGG pathway enrichment analysis was conducted (Fig. 6). All of the pathways with a p value <0.05 were screened out and ranked by p value. The top three pathways were the cancer, estrogen signaling and colorectal cancer pathways.

Fig. 5
figure 5

Biological process analysis of active components

Full size image
Fig. 6
figure 6

KEGG pathway enrichment analysis of active components

Full size image

Pathway–target–component network construction

The analysis of active ingredients, corresponding targets and signaling pathways is shown in detail in Fig. 7. From these results, emodin, quercetin, liriodenine, chrysophanol and kaempferol were the key components contributing to the antioxidant effect of R. tanguticum seeds. The top three key targets were ESR1, APP and MAPK8. Using the KEGG mapper tool to obtain the pathway map of R. tanguticum seeds in the treatment of oxidative disorders, we screened the top four pathways and integrated the final pathway map (Fig. 8). The target is marked in light color, while the potential target of the antioxidant is marked in dark color. The figure shows that the antioxidant targets of R. tanguticum seeds were scattered among the pathways of cancer, estrogen signaling, colorectal cancer and Chagas disease signaling and that the seed extract primarily functioned by regulating these pathways. Most targets could function in multiple pathways, such as JUN, AKT1 and MAPK8.

Fig. 7
figure 7

Active component-target-signal pathway network of R. tanguticum seeds

Full size image
Fig. 8
figure 8

Molecular docking pattern and mapping surface showing molecules occupying the active pocket of proteins (A and B, PTGS2-liriodenine; C and D, PTGS2-chrysophanol; E and F, PTGS2-kaempferol)

Full size image

Molecular docking of active components and key targets

Five active ingredients and the top three targets ranked by degree were selected to conduct molecular docking (Table 4). Following convention, a binding capacity between the tested molecules and proteins was assumed to exist when the binding energy score was greater than 4.25. Scores greater than 5.0 indicate relatively high binding affinity, and scores greater than 7.0 indicate strong ligand–receptor interaction [49]. Hence, the selected active ingredients (liriodenine, chrysophanol and kaempferol) were docked one to one with PTGS2 using AutoDock according to the binding energy (>7.0). Liriodenine could form a hydrogen bond with PTGS2 at His-39 and Tyr-130. Chrysophanol could form a hydrogen bond with PTGS2 at Cys-47 and His-39, while kaempferol could form a hydrogen bond with PTGS2 at Thr-206 and Trp-387 (Fig. 9).

Table 4 Molecular docking results of active components from seeds and potential targets of antioxidant
Full size table
Fig. 9
figure 9

Potential antioxidant pathway of the main active ingredients of R. tanguticum seeds (↑ arrows indicate a promotion effect; T arrows indicate an inhibition effect). The target is marked in light color, and the potential antioxidant target of R. tanguticum seeds is marked in dark color

Full size image

Discussion

Antioxidant activity has become a property of interest in functional foods. The use of natural antioxidants from plants (especially seeds), considered to be a substitute for synthetic antioxidants, has gradually become a trend [9]. Numerous studies have revealed that many components of R. tanguticum have significant antioxidant activities [40, 50]. Its seeds have a high soluble protein content and are rich in many amino acids and other nutritional components, according to previous data from our laboratory. Thus, it is of great significance to study the antioxidant mechanisms of R. tanguticum seeds.

The results of the three antioxidant assays verified that R. tanguticum seed extracts had strong scavenging effects on DPPH and ABTS radicals and high FRAP ability. The highest scavenging rate achieved by DPPH (85.5%) was lower than those previously reported for green tea and rosemary extracts (> 90%), which hold pioneering and instructive roles as natural antioxidants [51]. However, compared with the scavenging rate of the positive control (VC), the IC50 for R. tanguticum seed extracts was lower. This showed that within a specific concentration range, R. tanguticum seed extracts had better antioxidant activity than VC. Moreover, R. tanguticum seed extracts exhibited superior antioxidant activity (IC50 = 12.31 mg/L) when compared with goji, as the DPPH scavenging activity for the latter was 784 mg/L [52]. For ABTS radical scavenging, our results showed that the activity of R. tanguticum seed extracts (0.78 mmol/L) was lower than that of flaxseed meal (1.19 mmol/L) [53]. However, the total FRAP reducing ability was higher than those of grape seed oil (0.735 mmol/L) and Origanum vulgare subsp. vulgare essential oil (467.25 μmol/L) [54, 55]. The good antioxidant activity of R. tanguticum seeds may be attributable to the phenolics and flavonoids in the extracts. The LC-Q-TOF/MS qualitative results revealed that the main active components of our aqueous extract included flavonoids, polyphenols, alkaloids, anthocyanins and organic acids. Flavonoids and polyphenols are primary contributors to the antioxidative process [56, 57].

To determine the compounds primarily responsible for the antioxidant activity of R. tanguticum seeds, network pharmacology was then carried out. After Lipinski’s rule of five and the ADME filter process, 15 compounds were chosen for target prediction, and 5 of them were predicted to be core components. The PPI network was analyzed by MCODE to obtain the hub genes (ESR1, APP, MAPK8, HSP90AA1, AKT1, MMP2, PTGS2, TGFB1 and JUN). The ESR1 gene encodes an estrogen receptor alpha, and the antioxidant properties of estrogen might contribute to decreased oxidative stress [58, 59]. Chen et al. demonstrated that inflammation and oxidative stress phenomena occurred in the cerebrum and cortex of APP transgenic mice [60]. MAPK8/9/10 activation is an important upstream signal to trigger autophagy, and autophagy can rescue apoptosis caused by mild oxidative stress [11, 61]. The MAPK pathway lies upstream of JUN and can activate JUN expression. JUN is one of the components of AP-1, a transcription factor that regulates inflammatory response genes [62]. Growing evidence has revealed that flavonoids exert good anti-inflammatory effects as well as increased antioxidant activity [63]. Therefore, the antioxidant mechanisms of R. tanguticum seeds may be achieved by controlling inflammatory reactions and autophagy.

In the GO enrichment and KEGG pathway analyses, these genes were mainly enriched in the cancer, estrogen signaling and colorectal cancer pathways. Thus, it can be seen that the antioxidant effect is associated with multiple diseases. Relieving oxidative stress is an effective strategy to prevent or treat cancer and other diseases. R. tanguticum seeds may exert antioxidant effects through these signaling pathways and via biological processes such as the positive regulation of nitric oxide. In addition, the location of the target was assigned, and the pathway diagram was plotted, suggesting the pivotal role of hub genes (such as MAPK8, AKT1 and ESR1) in these pathways.

Molecular docking was used in this study to clarify the mechanism and provide valuable guidance for drug screening and design in future experiments. In our study, liriodenine was found to be one of the best choices for drug–target interactions with PTGS2. Liriodenine has been proven to have powerful antibacterial and antioxidant activities [64]. It shows strong activity in the prevention of dementia. However, the content of liriodenine in plants is very low (generally only 0.01%), which would be a bottleneck for the use of liriodenine in potential medicinal applications [65]. In our molecular docking experiment, chrysophanol also had a relatively high binding energy score with PTGS2 (7.10). According to previous studies, chrysophanol has antioxidant and senescence resistance properties and is being considered as a drug candidate for various neurodegenerative diseases [66, 67]. It is speculated that the hydroxyl (·OH) in chrysophanol conducts a one-electron conversion reaction with the superoxide anion (·O2−), which inhibits the autoxidation of pyrogallol and consequently exhibits a free radical scavenging effect. Therefore, chrysophanol may be a natural antioxidant that could be used as a food ingredient. More experiments in the future are required to verify this relationship and the mechanisms involved.

This study showed that R. tanguticum seed extracts produced antioxidant effects through synergism between multiple ingredients, targets and pathways. The mechanisms of action were elucidated through applied network pharmacology. These results suggest that the seeds may be used as a functional food supplement or further developed as a natural antioxidant.

Conclusion

R. tanguticum seeds were shown to have good antioxidant capacity through DPPH, ABTS and FRAP assays. A total of 24 components in the seed extracts were identified by LC-Q-TOF/MS. The seed extracts were rich in flavonoids, organic acids, polyphenols and other substances. Five potential compounds and nine associated targets were identified using the network pharmacological approach. Emodin, quercetin, liriodenine, chrysophanol and kaempferol were the central components contributing to antioxidant activity. The core targets were ESR1, APP, MAPK8, HSP90AA1, AKT1, MMP2, PTGS2, TGFB1 and JUN. The crucial signaling pathways were identified to be cancer, colorectal cancer, estrogen signaling and MAPK signaling. In view of these results, the component–target–pathway network was constructed. A further integrated pathway diagram revealed that hub genes had core positions in the signaling pathway. These results might provide new insights for future research into the mechanisms behind the antioxidant effects of R. tanguticum seeds.

Molecular docking showed that all five potential drug compounds (emodin, quercetin, liriodenine, chrysophanol and kaempferol) had high binding energies to the predicted target proteins (AKT1, ESR1 and PTGS2). The binding energy score between liriodenine and PTGS2 was the highest (8.16), followed by that of chrysophanol (7.10). This result supports the potential for PTGS2-targeted drug screening and design.

Availability of data and materials

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Abbreviations

R. tanguticum :

Rheum tanguticum

TCM:

Traditional Chinese Medicine

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

ABTS:

2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)

FRAP:

Ferric ion reducing antioxidant power

PPI:

Protein-protein interaction network

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

References

  1. Xin Y, Yang Y, Yu K, et al. Filtration of Active Components with Antioxidant Activity Based on the Differing Antioxidant Abilities of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus through UPLC/MS Coupling with Network Pharmacology. J Evid-Based Complementary Altern Med. 2021;5547976. https://doi.org/10.1155/2021/5547976.

  2. Ishihara Y, Takemoto T, Ishida A, et al. Protective actions of 17beta-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds. Oxidative Med Cell Longev. 2015;343706. https://doi.org/10.1155/2015/343706.

  3. Zhang M, Lu Y, Chen Y, et al. Insufficiency of melatonin in follicular fluid is a reversible cause for advanced maternal age-related aneuploidy in oocytes. Redox Biol. 2020;28:101327. https://doi.org/10.1016/j.redox.2019.101327.

    Article  CAS  PubMed  Google Scholar 

  4. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909–50. https://doi.org/10.1152/physrev.00026.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aynur S, Çeken TB, Emen TS, et al. Assessment of the Antioxidant Activity of Silybum marianum Seed Extract and Its Protective Effect against DNA Oxidation, Protein Damage and Lipid Peroxidation. Food Technol Biotechnol. 2016;54(4):455–61. https://doi.org/10.17113/ftb.54.04.16.4323.

    Article  CAS  Google Scholar 

  6. Ghosh T, Basu A, Adhikari D, et al. Antioxidant activity and structural features of Cinnamomum zeylanicum. 3. Biotech. 2015;5(6):939–47. https://doi.org/10.1007/s13205-015-0296-3.

    Article  Google Scholar 

  7. Tang L, Sun J, Zhang HC, et al. Evaluation of physicochemical and antioxidant properties of peanut protein hydrolysate. PLoS One. 2012;7(5):e37863. https://doi.org/10.1371/journal.pone.0037863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kang SJ, Choi BR, Kim SH, et al. Dried pomegranate potentiates anti-osteoporotic and anti-obesity activities of red clover dry extracts in ovariectomized rats. Nutrients. 2015;7(4):2622–47. https://doi.org/10.3390/nu7042622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Munekata PES, Gullon B, Pateiro M, et al. Natural Antioxidants from Seeds and Their Application in Meat Products. Antioxidants (Basel). 2020;9:815. https://doi.org/10.3390/antiox9090815.

    Article  CAS  Google Scholar 

  10. Li P, Feng B, Jiang H, et al. A Novel Forming Method of Traditional Chinese Medicine Dispersible Tablets to Achieve Rapid Disintegration Based on the Powder Modification Principle. Sci Rep. 2018;8(1):10319. https://doi.org/10.1038/s41598-018-28734-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu WN, Zheng HL, Yang RZ, et al. Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy. Exp Mol Med. 2019;51(11):1–16. https://doi.org/10.1038/s12276-019-0331-2.

    Article  CAS  PubMed  Google Scholar 

  12. Banerjee S, Bhattacharjee P, Kar A, et al. LC-MS/MS analysis and network pharmacology of Trigonella foenum-graecum - A plant from Ayurveda against hyperlipidemia and hyperglycemia with combination synergy. Phytomedicine. 2019;60:152944. https://doi.org/10.1016/j.phymed.2019.152944.

    Article  CAS  PubMed  Google Scholar 

  13. Silinsin M, Bursal E. UHPLC-MS/MS phenolic profiling and in vitro antioxidant activities of Inula graveolens (L.) Desf. Nat. Prod. Res. 2017;32(12):1467–71. https://doi.org/10.1080/14786419.2017.1350673.

    Article  CAS  Google Scholar 

  14. Aras A, Bursal E, Alan Y, et al. Polyphenolic content, antioxidant potential and antimicrobial activity of Satureja boissieri. Iran J Chem Chem Eng. 2018;37(6):209–19.

    CAS  Google Scholar 

  15. Pham DQ, Ba DT, Dao NT, et al. Antimicrobial efficacy of extracts and constituents fractionated from Rheum tanguticum Maxim. ex Balf. rhizomes against phytopathogenic fungi and bacteria. Ind Crops Prod. 2017;108:442–50. https://doi.org/10.1016/j.indcrop.2017.06.067.

    Article  CAS  Google Scholar 

  16. Wang A, Li W. Genetic diversity of Rheum tanguticum (Polygonaceae), an endangered species on Qinghai-Tibetan Plateau. Biochem Syst Ecol. 2016;69:132–7. https://doi.org/10.1016/j.bse.2016.09.006.

    Article  CAS  Google Scholar 

  17. Liu H, Xu W, Shen J, et al. Determination of Amino Acids in Rhubarb Seeds with DNFB Pre-column Derivatization by Reversed-phase High Performance Liquid Chromatography. Nat Prod Res Dev. 2014;26(07):1056–61. https://doi.org/10.16333/j.1001-6880.2014.07.004.

    Article  CAS  Google Scholar 

  18. Liu H, Tan L, Xu W, et al. Determination of the Concentrations of Protein, Polysaccharides, Starch Detected in Rhubarb Seeds. Chin J Spectrosc Lab. 2013;30(06):3114–21.

    CAS  Google Scholar 

  19. Shu GW, He YX, Lei N, et al. Cellulase-Assisted Extraction of Polysaccharides from White Hyacinth Bean: Characterization of Antioxidant Activity and Promotion for Probiotics Proliferation. Molecules. 2017;22:1764. https://doi.org/10.3390/molecules22101764.

    Article  CAS  PubMed Central  Google Scholar 

  20. Dong X, Fu J, Yin X, et al. Emodin: A Review of its Pharmacology. Toxicity Pharmacokin Phytother Res. 2016;30(8):1207–18. https://doi.org/10.1002/ptr.5631.

    Article  CAS  Google Scholar 

  21. Subramanya SB, Venkataraman B, Meeran MFN, et al. Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury. Int J Mol Sci. 2018;19(12):3776. https://doi.org/10.3390/ijms19123776.

    Article  CAS  PubMed Central  Google Scholar 

  22. Dong X, Huang Y, Wang Y, et al. Anti-inflammatory and antioxidant jasmonates and flavonoids from lychee seeds. J Funct Foods. 2019;54:74–80. https://doi.org/10.1016/j.jff.2018.12.040.

    Article  CAS  Google Scholar 

  23. Xu Y, Chen G, Guo M. Correlations between phytochemical fingerprints of Moringa oleifera leaf extracts and their antioxidant activities revealed by chemometric analysis. Phytochem Anal. 2020;32:14. https://doi.org/10.1002/pca.3016.

    Article  CAS  Google Scholar 

  24. Bursal E, Ylmaz MA, Izol E, et al. Enzyme inhibitory function and phytochemical profile of Inula discoidea plant species with in vitro spectrophotometric methods and in silico molecular docking analysis. Biophys Chem. 2021;277:106629. https://doi.org/10.1016/j.bpc.2021.106629.

    Article  CAS  PubMed  Google Scholar 

  25. Gao K, Song YP, Song A. Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology. BioData Min. 2020;13(1):19. https://doi.org/10.1186/s13040-020-00229-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zeng Q, Li L, Jin Y, et al. A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer’s Disease. Evid-Based Complement Altern Med. 2019;2019:8706589. https://doi.org/10.1155/2019/8706589.

    Article  Google Scholar 

  27. Babgi BA, Alsayari J, Alenezi HM, et al. Alteration of Anticancer and Protein-Binding Properties of Gold(I) Alkynyl by Phenolic Schiff Bases Moieties. Pharmaceutics. 2021;13(4):461. https://doi.org/10.3390/pharmaceutics13040461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mu C, Sheng Y, Wang Q, et al. Potential compound from herbal food of Rhizoma Polygonati for treatment of COVID-19 analyzed by network pharmacology: Viral and cancer signaling mechanisms. J Funct Foods. 2021;77:104149. https://doi.org/10.1016/j.jff.2020.104149.

    Article  CAS  PubMed  Google Scholar 

  29. Zhou W, Chen Z, Li W, et al. Systems pharmacology uncovers the mechanisms of anti-asthma herbal medicine intervention (ASHMI) for the prevention of asthma. J Funct Foods. 2019;52:611–9. https://doi.org/10.1016/j.jff.2018.11.048.

    Article  CAS  Google Scholar 

  30. Xiong F, Nie XQ, Yang LC, et al. Non-target metabolomics revealed the differences between Rh tanguticum plants growing under canopy and open habitats. BMC Plant Biol. 2021;21:119. https://doi.org/10.1186/s12870-021-02897-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Parisi OI, Aiello D, Casula MF, et al. Mesoporous nanocrystalline TiO2 loaded with ferulic acid for sunscreen and photo-protection: safety and efficacy assessment. RSC Adv. 2016;6(87):83767–75. https://doi.org/10.1039/c6ra07653j.

    Article  CAS  Google Scholar 

  32. Re R, Pellegrini N, Proteggente A, et al. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26(9):1231–7. https://doi.org/10.1016/S0891-5849(98)00315-3.

    Article  CAS  PubMed  Google Scholar 

  33. Frontinan-Rubio J, Gomez MV, Gonzalez VJ, et al. Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells. Sci Rep. 2020;10(1):18407. https://doi.org/10.1038/s41598-020-75448-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yun YR, Park SH, Kim IH. Antioxidant effect of Kimchi supplemented with Jeju citrus concentrate and its antiobesity effect on 3T3-L1 adipocytes. Food Sci Nutr. 2019;7(8):2740–6. https://doi.org/10.1002/fsn3.1138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47(W1):W357–64. https://doi.org/10.1093/nar/gkz382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gil S, Naomi R, Inbar P, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016;54(30):1–33. https://doi.org/10.1002/cpbi.5.

    Article  Google Scholar 

  37. Hosen SMZ, Saha D, Dash R, et al. Drug Bank: An Update-Resource for in Silico Drug Discovery. Res J Pharm Dosage Forms Technol. 2012;4(3):166–71.

    Google Scholar 

  38. Janet P, Núria QR, Àlex B, et al. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database:bav. 2015;2015:bav028. https://doi.org/10.1093/database/bav028.

    Article  CAS  Google Scholar 

  39. Amberger JS, Bocchini CA, Scott AF, et al. A. OMIM.org: leveraging knowledge across phenotype–gene relationships. Nucleic Acids Res. 2019;47(D1):D1038–43. https://doi.org/10.1093/nar/gky1151.

    Article  CAS  PubMed  Google Scholar 

  40. Serhat K, Fatma K, Mustafa K, et al. Bioactive contents, In vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts. Nat. Prod. Res. 2019;43(23):3353–7. https://doi.org/10.1080/14786419.2018.1560294.

    Article  CAS  Google Scholar 

  41. The Gene Ontology, C. Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Res. 2017;45(D1):D331–8. https://doi.org/10.1093/nar/gkw1108.

    Article  CAS  Google Scholar 

  42. Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 2000;28:27–30. https://doi.org/10.1093/nar/28.1.27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019;28:1947–51. https://doi.org/10.1002/pro.3715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kanehisa M, Furumichi M, Sato Y, et al. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49:D545–51. https://doi.org/10.1093/nar/gkaa970.

    Article  CAS  PubMed  Google Scholar 

  45. Wei HD, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1). https://doi.org/10.1038/nprot.2008.211.

  46. Kim S, Chen J, Cheng T, et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 2019;47(D1):D1102–9. https://doi.org/10.1093/nar/gky1033.

    Article  PubMed  Google Scholar 

  47. Goodsell DS, Zardecki C, Di Costanzo L, et al. RCSB Protein Data Bank: Enabling biomedical research and drug discovery. Protein Soc. 2020;29(1):52–65. https://doi.org/10.1002/pro.3730.

    Article  CAS  Google Scholar 

  48. Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26. https://doi.org/10.1016/S0169-409X(00)00129-0.

    Article  CAS  PubMed  Google Scholar 

  49. Piao C, Zhang Q, Jin Wang L, et al. A Study on the Mechanism of Milkvetch Root in the Treatment of Diabetic Nephropathy Based on Network Pharmacology. Evid-Based Complement Altern Med. 2020;2020:6754761. https://doi.org/10.1155/2020/6754761.

    Article  Google Scholar 

  50. Silveira JP, Seito LN, Eberlin S, et al. Photoprotective and antioxidant effects of Rhubarb: inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes. BMC Complement Altern Med. 2013;13:49. https://doi.org/10.1186/1472-6882-13-49.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Castro FVR, Andrade MA, Sanches Silva A, et al. The Contribution of a Whey Protein Film Incorporated with Green Tea Extract to Minimize the Lipid Oxidation of Salmon (Salmo salar L.). Foods. 2019;8(8):327. https://doi.org/10.3390/foods8080327.

    Article  CAS  PubMed Central  Google Scholar 

  52. Skenderidis P, Lampakis D, Giavasis I, et al. Chemical Properties, Fatty-Acid Composition, and Antioxidant Activity of Goji Berry (Lycium barbarum L. and Lycium chinense Mill.) Fruits. Antioxidants (Basel). 2019;8:60. https://doi.org/10.3390/antiox8030060.

    Article  CAS  Google Scholar 

  53. Zhang W, Zhang J, Zhou H, et al. Preparation of Small Molecular Antioxidant Peptides from Flaxseed Meal. Food Sci. 2020;41(08):36–44.

    Google Scholar 

  54. Vazirian M, Mohammadi M, Farzaei MH, et al. Chemical composition and antioxidant activity of Origanum vulgare subsp. vulgare essential oil from Iran. Res J Pharmacogn. 2015;2(1):41–6.

    Google Scholar 

  55. Lin T, Lu Z, Liu G, et al. Fatty acid composition and antioxidant activity of grape seed oil and its application in edible lipstick. China Oils Fats. 2021;46(03):118–21. https://doi.org/10.19902/j.cnki.zgyz.1003-7969.2021.03.023.

    Article  CAS  Google Scholar 

  56. Song CF, Chin LH, Gow CY. Anti-inflammatory effects of phenolic compounds isolated from the fruits of Artocarpus heterophyllus. J Agric Food Chem. 2008;56(12):4463–8. https://doi.org/10.1021/jf800444g.

    Article  CAS  Google Scholar 

  57. Sun J, Qiu C, Ding Y, et al. Fulvic acid ameliorates drought stress-induced damage in tea plants by regulating the ascorbate metabolism and flavonoids biosynthesis. BMC Genomics. 2020;21(1):411. https://doi.org/10.1186/s12864-020-06815-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Koregol AC, Kalburgi NB, Kanniappa SS, et al. 8-Isoprostane in chronic periodontitis and type II diabetes: Exploring the link. J Dent Res Dent Clin Dent Prospects. 2018;12(4):252–7. https://doi.org/10.15171/joddd.2018.039.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sharma M, Barai RS, Kundu I, et al. PCOSKBR2: a database of genes, diseases, pathways, and networks associated with polycystic ovary syndrome. Sci Rep. 2020;10(1):14738. https://doi.org/10.1038/s41598-020-71418-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chen J, Gao L, Ren J, et al. Study on the anti-inflammatory and anti-oxidative stress of acteoside in APP/PS1 double-transgenic mice. Chin J Hosp Pharm. 2020;40(12):1307–1311+1363. https://doi.org/10.13286/j.1001-5213.2020.12.06.

    Article  CAS  Google Scholar 

  61. Dong Y, Yin S, Jiang C, et al. Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer cells. Autophagy. 2014;10(2):296–310. https://doi.org/10.4161/auto.27210.

    Article  CAS  PubMed  Google Scholar 

  62. Liu Y, Wu X, Jin W, et al. Immunomodulatory Effects of a Low-Molecular Weight Polysaccharide from Enteromorpha prolifera on RAW 264.7 Macrophages and Cyclophosphamide- Induced Immunosuppression Mouse Models. Mar Drugs. 2020;18:340. https://doi.org/10.3390/md18070340.

    Article  CAS  PubMed Central  Google Scholar 

  63. Xian Y, Zhang J, Bian Z, et al. Bioactive natural compounds against human coronaviruses: a review and perspective. Acta Pharm Sin B. 2020;10(7):1163–74. https://doi.org/10.1016/j.apsb.2020.06.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nissanka APK, Karunaratne V, Bandara BMR, et al. Antimicrobial alkaloids from Zanthoxylum tetraspermum and caudatum. Phytochemistry. 2001;56(8):857–61. https://doi.org/10.1016/S0031-9422(00)00402-7.

    Article  CAS  PubMed  Google Scholar 

  65. Liu Y, Chen Z, Peng Y, et al. Research Progress on Liriodenine. Chem Ind For Prod. 2011;31(04):109–16.

    Google Scholar 

  66. Fuqing L, Chen Z, Xian Z, et al. Chrysophanol affords neuroprotection against microglial activation and free radical-mediated oxidative damage in BV2 murine microglia. Int J Clin Exp Med. 2015;8(3):3447–55.

    Google Scholar 

  67. Shen CY, Jiang JG, Yang L, et al. Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. Br J Pharmacol. 2017;174(11):1395–425. https://doi.org/10.1111/bph.13631.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to appreciate all editors/reviewers for their helpful comments and valuable suggestions.

Funding

This work was funded by the National Key Research and Development Program: Whole Process Monitoring Technology and Demonstration of Qilian Mountain Nature Reserve (2019YFC0507404) and the China Academy of Sciences-Qinghai National Park Joint Project: Research and Development of Livelihood Improvement Model and Technology Integration of Sanjiangyuan National Park (LHZX-2020-09).

Author information

Authors and Affiliations

  1. Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, China

    Lingling Wang, Shuo Zhao, Yang Yang & Guoying Zhou

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Lingling Wang, Shuo Zhao & Yang Yang

  3. China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Feng Xiong

Authors
  1. Lingling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuo Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guoying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Lingling Wang: Conceptualization, Methodology, Writing - original draft. Feng Xiong: Data curation, Investigation, Software. Shuo Zhao: Visualization, Validation. Yang Yang: Investigation. Guoying Zhou: Writing - review & editing, Supervision. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Guoying Zhou.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

The collection of plant material comply with relevant institutional, national, and international guidelines and legislation. We have permission to collect Rheum tanguticum seeds. The voucher specimens and their information were deposited at the Qinghai-Tibetan Plateau Museum of Biology, CAS, China (QHGC-1800).

Consent for publication

Not applicable.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Xiong, F., Zhao, S. et al. Network pharmacology combined with molecular docking to explore the potential mechanisms for the antioxidant activity of Rheum tanguticum seeds. BMC Complement Med Ther 22, 121 (2022). https://doi.org/10.1186/s12906-022-03611-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12906-022-03611-3

Keywords

BMC Complementary Medicine and Therapies

ISSN: 2662-7671

Contact us