Startseite Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation
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Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation

  • Cheng Li , Hongli Jiang , Jingchun Yao , Xulong Chen EMAIL logo und PuXun Tian EMAIL logo
Veröffentlicht/Copyright: 27. April 2023
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Open Chemistry
Aus der Zeitschrift Open Chemistry Band 21 Heft 1

Abstract

Radix puerariae has become the most commonly used medicine for diabetic nephropathy (DN). However, the mechanism of Radix puerariae in the treatment of DN is not completely clear. This study is to determine the active ingredients, targets, and signaling pathways of Radix puerariae for the treatment of DN using network pharmacology analysis and animal experiments to confirm its possible mechanism of action. A total of 12 potential effective components and 10 key therapeutic targets were obtained. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the use of Radix puerariae in DN treatment mainly involves HIF-1 signaling pathway, TNF signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway, FoxO signaling, and VEGF signaling pathway. Molecular docking proved that the combined activity of the components with potential key targets were excellent. Animal experiments showed that Radix puerariae could improve the renal pathological structure in DN rats. Radix puerariae could decrease the content of AKT1, IL-6, INS, and reduce the expression levels of p-Akt/Akt and p-FoxO1/FoxO1 in renal tissue of DN rats. This study provides insight into the therapeutic potential and molecular mechanisms of Radix puerariae for treating DN.

Keywords: Radix puerariae ; diabetic nephropathy; network pharmacology; molecular docking; FoxO1 signaling pathway

1 Introduction

Diabetic nephropathy (DN) is a chronic non-communicable condition that adversely affects the health and quality of life of diabetes patients. DN has now emerged as the most common cause of end-stage renal disease (ESRD) in Europe, the United States, and Japan. In addition, as the life expectancy of the general population increases, the obesity rate increases, and the sedentary lifestyle leads to an increase in the incidence of diabetes and its chronic complications, the number of patients affected in some developing countries is rapidly increasing. Patients and the healthcare system are facing significant challenges [1,2]. According to the latest US Renal Data System, from 1990 to 2013, the annual mortality rate of DN has increased by more than two-fold (from 1.4 to 2.9 per 100,000 populations) [3]. Modern medical molecular biology found that the pathogenesis of DN is undoubtedly multi-factorial. During the development of DN, various cellular events and signaling pathways are activated, and the activated signaling pathways are regulated by a large number of molecules, which regulate each other’s biological activities [4]. At present, there are no targeted specific drugs for the treatment of DN, which mainly delay the progression of DN by improving lifestyle, controlling blood sugar, controlling blood pressure, and correcting lipid metabolism disorders [5]. Studies [6,7] have confirmed that the efficacy of combined traditional Chinese and western medicine in the treatment of DN is better than that of western medicine alone. Therefore, exploring the research of traditional Chinese medicine in the treatment of DN has important socio-economic significance.

Radix puerariae, a traditional Chinese medicine, was first published in the “Shen Nong’s Materia Medica,” “mainly diminishes thirst” and enters the spleen and stomach meridian. Because it promotes body fluid and quenches thirst, it has become the most commonly used medicine for diabetes in the category of “diminishing thirst” in Chinese medicine. Puerarin is the main effective constituent separated and extracted from the dried roots of Radix puerariae, and it is also an effective natural, free radical scavenger. The chemical name for this compound is 4,7-dihydroxy-8-β-d-glucosyl isoflavones [8]. Modern pharmacological studies have demonstrated that purerarin reduces blood sugar levels, improves insulin resistance, protects islets, inhibits inflammation, reduces oxidative stress, prevents Maillard reactions, and prevents advanced glycation end products in diabetes patients [9]. In addition, puerarin plays an important role in clinical treatment by delaying and improving a series of complications of diabetes. It inhibits renal oxidative stress, improves vascular endothelial dysfunction, protects glomerular podocytes, and reduces renal tubular interstitial damage [10]. However, its targets and mechanisms are not yet clear.

Network pharmacology has evolved from rapid developments in computer science and systems biology. This process makes use of a number of technologies, such as omics, high-throughput screening, network visualization, and network analysis. As a result of the complex network analysis, drugs are systematically predicted to affect the disease network in accordance with the multi-pathway and multi-target characteristics of traditional Chinese medicine [11]. In this study, network pharmacology is used to predict and analyze the effective components, therapeutic targets, and signal pathways of Radix puerariae for DN treatment. The above molecules were verified in animal studies to provide evidence for further technical research and the application of Radix puerariae as a treatment for DN (Figure 1).

Figure 1 Schematic flowchart of the study design.
Figure 1

Schematic flowchart of the study design.

2 Materials and methods

2.1 Methods

2.1.1 Network pharmacology study

2.1.1.1 Identification and screening of the main constituents and targets of Radix puerariae

The active ingredients of Radix puerariae were screened using the TCMSP platform (http://lsp.nwu.edu.cn/tcmsp.php) [12] of the Chinese Medicine System Pharmacology Database and related literature from CNKI (https://www.cnki.net/) and PubMed databases (https://pubmed.ncbi.nlm.nih.gov/). Oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18 served as the basis for initial screening [13]. According to the selected constituents, the target protein name was obtained from the “Targets Information” in the TCMSP platform, and then the active components that did not correspond to the target protein were deleted. Additionally, the targets from the “homo sapiens” source have been converted into the corresponding genes by using the UniProt database (http://www.uniport.org) for further analysis. A network diagram of the active ingredient-target relationship was drawn using Cytoscape 3.8.

2.1.2 Obtaining the key targets of Radix puerariae against DN

“Nephropathies, Diabetic” as the keyword, and the DN-related target information were retrieved from GeneCards (https://www.genecards.org/) and DisGeNET databases (https://www.disgenet.org/). Finally, Venn2.1.0 software (https://bioinfogp.cnb.csic.es/tools/venny/index.html) was applied to map the potential targets of Radix puerariae and DN-related targets to obtain the common targets of Radix puerariae-DN.

“Drug-disease” targets were imported into the STRING database (https://string-db.org/), and the maximum number of interactions were designed to not exceed ten interactors in order to structure PPI (protein–protein interaction) diagram. The results saved in TSV format were imported into Cytoscape 3.8.0, and algorithms of cytoHubba plug-in with Degree values were used to determine the core targets of Radix puerariae against DN.

2.1.3 Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and construction of the “component-target-pathway” network

In order to understand the function of the selected core genes and their roles in the signaling pathway, the core targets were imported into the DAVID 6.8 (https://david.ncifcrf.gov/) database for GO and KEGG enrichment analysis. The “component-target-pathway” interaction network was formed using Cytoscape 3.8.0.

2.1.4 Molecular docking study

Molecular docking was performed on the top three effective components and key genes related to DN to determine whether the ingredients were related to the targets. The Protein Data Bank (http://www.rcsb.org/pdb) and PubChem databases (https://pubchem.ncbi.nlm.nih.gov/) were utilized to obtain three-dimensional chemical structures of the targets and components. The final docking conformation was determined using AutoDock Vina software in order to determine the best conformation for affinity.

2.2 Experimental verification

2.2.1 Materials and reagents

Radix puerariae was provided by Jiangxi Xun Fengtang Traditional Chinese Medicine Co., Ltd, identified by Professor Gao Chunhua of Jiujiang University as a genuine product. In addition, herbs were morphologically authenticated by a Chinese herbalist and chemically tested by thin layer chromatography, as per the Chinese Pharmacopoeia 2020 [14].

Preparation of Radix puerariae extract: Radix puerariae 30 g was decocted twice with water (300 mL and then 225 mL) for 2 h and the extracted solution was concentrated to 30 mL to obtain Radix puerariae extract [15].

2.2.2 Experimental animals

Sprague Dawley (SD) rats (5 weeks old, 120 ± 10 g) were purchased from SPF Biotechnology Co., Ltd (Beijing, China) and raised in a quiet room with a temperature of 20–28°C, relative humidity of 60%, and alternating time of light and dark 12/12 h for 1 week before treatment. These animals had sufficient standard feed and ensured freedom of drinking water. This study was approved by the Medical Ethics Committee of Jiujiang University Affiliated Hospital, Jiujiang, China (protocol approval number: jjuhmer-a-2022-02; approval date: 15 April 2022).

2.2.3 Experimental designs

A week after adapting to the diet, the control group rats received common food and the model group rats received high-fat food for 4 weeks. After fasting for 12 h, rats in the model group were given an intraperitoneal injection of streptozotocin (STZ; 30 mg/kg) once a day for 72 h, while the control group was treated with citrate buffer of equal volume as placebo. After 72 h of STZ injection, if blood glucose was more than 16.6 mmol/L for three consecutive days, urine glucose was strongly positive, and urine protein content at 24 h was more than 30 mg, the DN model was confirmed to be successful.

Rats with successful modeling were assigned randomly to either the DN (n = 10) or the DN + Radix puerariae (n = 10) group. Radix puerariae treatment began on the first day after successful modeling and continued for 5 weeks. Radix puerariae was suspended in distilled water and given at a dose of 3.2 g/kg/day. Rats in the DN group received the same volume of distilled water. At the end of the intervention, all rats were euthanized after anesthesia, and both kidneys of each animal were removed after 5 weeks of treatment. Kidneys were fixed in neutral polyformaldehyde for 48 h, then sliced into sections of 4 µm, embedded in paraffin for staining. HE, Masson trichome, and PASM staining were conducted according to the instructions of the respective kit. The remaining kidney tissues were put into sterile EP tubes and stored at −80°C for polymerase chain reaction (PCR) and western blotting analysis.

2.2.4 Quantitative real-time PCR

Total RNA was extracted from renal cortical tissue with TransZol Up (TransGen Biotech, Beijing, China) according to the manufacturer’s protocols, then reversely transcribed into cDNA using EasyScript One-Step gDNA Removal and cDNA Synthesis Supermix (TransGen Biotech, Beijing, China). PCR primers were designed with the Primer Express 5.0 software and synthesized by Sangon Biotech Co., Ltd (Shanghai, China). The ratio of specific mRNA:GAPDH mRNA was calculated using the 2−ΔΔCT method. Primers used to amplify IL-6, INS, TNF, AKT1, VEGFA, IGF1, and GAPDH are shown in Table S1.

2.2.5 Western blotting analysis

The total protein of each rat’s kidney tissue was extracted by RIPA lysate (Solarbio, Beijing, China), the protein concentration was determined by BCA method (Thermo Fisher, 23223; or Micro BCA, Thermo Fisher, 23223). Briefly, protein quantification involves the following steps: adding appropriate volume of 5× Protein Loading Buffer, denaturing in boiling water bath, 10% SDS-PAGE gel for electrophoresis separation, PVDF membrane (Millipore, Billerica, MA, USA) transfer and sealing, and adding the corresponding primary antibodies. The membranes were incubated overnight at 4°C with primary antibodies including anti-AKT antibody (1:1,000; Proteintech, Chicago, IL, USA), anti-p-AKT antibody (1:1,000; Proteintech, Chicago, IL, USA), anti-FoxO1 antibody (1:1,000; HuaBio, Hangzhou, China), Anti-p-FoxO1 antibody (1:1,000; Abcam, Cambridge, MA, USA), and anti-β-actin antibody (1:50,000; Proteintech, Chicago, IL, USA), followed by incubation with a secondary antibody (1:5,000; Proteintech, Chicago, IL, USA) for 1–2 h. Bound antibodies were visualized using chemiluminescence detection on autoradiographic film. The protein bands were quantified by densitometry using ImageJ software. The levels of the detected proteins were normalized against β-actin.

2.3 Statistical analysis

SPSS 26.0 statistical software was used for data analysis. The measurement data conform to the normal distribution and the variance was homogeneous, one-way ANOVA was used for inter-group comparison. All data were expressed with mean values ± SD, P < 0.05 was considered statistically significant.

3 Results

3.1 Active ingredients and target prediction of Radix puerariae

Through TCMSP platform and literature search, the main chemical components and corresponding targets of Radix puerariae were obtained, a total of five active components were screened according to their DL and OB values. Puerarin, daidzein, daidzin, genistein, sitogluside, ononin, and 7,8,4′-trihydroxyisoflavone were in conformity with the standard, but according to some reports [16,17,18,19,20,21,22], these ingredients have high pharmacological activity, so this study also took these ingredients as bioactive compounds for further analysis. The TCMSP number, molecular name, and related parameters for each active ingredient are displayed in Table 1. After Uniprot screening and correction, a total of 209 targets of compounds were screened, and combined with 12 bioactive compounds, establishing the ingredient-target network (Figure 2).

Table 1

Basic information about the active components of Radix puerariae

Mol ID Molecule name Structure OB (%) DL
MOL000392 Formononetin 69.67 0.21
MOL000358 Beta-sitosterol 36.91 0.75
MOL002959 3′-Methoxydaidzein 48.57 0.24
MOL003629 Daidzein-4,7-diglucoside 47.27 0.67
MOL012297 Puerarin 24.03 0.69
MOL000390 Daidzein 19.44 0.19
MOL009720 Daidzin 14.32 0.73
MOL000481 Genistein 17.93 0.21
MOL000357 Sitogluside 20.63 0.62
MOL000391 Ononin 11.52 0.78
MOL004631 7,8,4′-Trihydroxyisoflavone 20.67 0.22
MOL012052 Tuberosine A 102.67 0.34
Figure 2 “Ingredient-target” network of Radix puerariae.
Figure 2

“Ingredient-target” network of Radix puerariae.

3.2 Intersection of disease targets and drug-disease targets

The GeneCards and DisGeNET databases provided 440 DN-related target genes (Figure 3). A Venn diagram analysis revealed 53 intersecting targets between Radix puerariae and DN (Figure 4).

Figure 3 Target genes related to DN.
Figure 3

Target genes related to DN.

Figure 4 Venn diagram of targets of Radix puerariae and DN.
Figure 4

Venn diagram of targets of Radix puerariae and DN.

3.3 Construction and screening of Radix puerariae-DN protein interaction network

The 53 intersection targets of “drug-disease” were uploaded to the STRING database to obtain the PPI network, then imported these data into Cytoscape software for visualization (Figure 5a and b). The network contained 53 nodes and 692 protein interaction relationships. The topological analysis indicated that the median values of Betweenness Centrality, Closeness Centrality, and Degree were 0.093, 0.729, and 26.1, respectively. Finally, ten key targets were screened from the Cytoscape software via the “CytoHubba” plug-in as shown in Figure 5c, including IL-6, INS, TNF, VEGFR, PTGS2, MMP9, AKT1, MAPK1, IGF1, and FN1.

Figure 5 Identification of Target genes for Radix puerariae treatment of DN. (a and b) PPI networks of the 53 intersecting targets. (c) The key targets of the PPI network.
Figure 5

Identification of Target genes for Radix puerariae treatment of DN. (a and b) PPI networks of the 53 intersecting targets. (c) The key targets of the PPI network.

3.4 Enrichment results of GO and KEGG pathways

We conducted GO function enrichment analysis on the top ten key targets using David 6.8 by setting the index to P < 0.05. A total of 114 GO items were obtained, including 99 items of biological processes, 6 items of cellular component, and 9 items of molecular function. The biological process items were the most important. Among them, the positive regulation of cell proliferation, positive regulation of glycogen biosynthetic process, negative regulation of the apoptotic process, and the positive regulation of glucose import were ranked high and were closely related to DN (Figure 6a–c).

Figure 6 Analysis of functional enrichment. (a) Top 20 biological processes. (b) Top 20 cellular components. (c) Top 20 molecular functions.
Figure 6 Analysis of functional enrichment. (a) Top 20 biological processes. (b) Top 20 cellular components. (c) Top 20 molecular functions.
Figure 6

Analysis of functional enrichment. (a) Top 20 biological processes. (b) Top 20 cellular components. (c) Top 20 molecular functions.

73 signal pathways were screened by KEGG enrichment pathway analysis (P < 0.05) using the DAVID 6.8 database, and the top 20 pathways were shown in Table 2 and Figure 7. Six of these pathways were related to DN’s occurrence and development, and Radix puerariae might be effective in treating DN by acting on the HIF-1 pathway, TNF pathway, mTOR pathway, PI3K-Akt pathway, FoxO pathway, and VEGF pathway. The FoxO pathway (Figure 8) was one of the top 20 signaling pathways that plays an important role in anti-apoptotic mechanisms. Among the FoxO signaling pathways, Akt and FOXO were the key proteins that mediate apoptotic processes.

Table 2

Analysis of the KEGG pathway of Radix puerariae in the treatment of DN

ID Term P value Genes
hsa05205 Proteoglycans in cancer 4.38 × 10−8 FN1, MAPK1, AKT1, IGF1, TNF, MMP9, VEGFA
hsa04066 HIF-1 signaling pathway 5.75 × 10−8 IL6, MAPK1, AKT1, IGF1, INS, VEGFA
hsa05200 Pathways in cancer 6.15 × 10−8 IL6, FN1, MAPK1, AKT1, IGF1, PTGS2, MMP9, VEGFA
hsa04668 TNF signaling pathway 9.94 × 10−8 IL6, MAPK1, AKT1, PTGS2, TNF, MMP9
hsa04150 mTOR signaling pathway 5.56 × 10−7 MAPK1, AKT1, IGF1, TNF, INS
hsa04151 PI3K-Akt signaling pathway 1.13 × 10−6 IL6, FN1, MAPK1, AKT1, IGF1, INS, VEGFA
hsa04068 FoxO signaling pathway 1.61 × 10−5 IL6, MAPK1, AKT1, IGF1, INS
hsa05161 Hepatitis B 2.20 × 10−5 IL6, MAPK1, AKT1, TNF, MMP9
hsa04370 VEGF signaling pathway 5.37 × 10−5 MAPK1, AKT1, PTGS2, VEGFA
hsa04510 Focal adhesion 8.75 × 10−5 FN1, MAPK1, AKT1, IGF1, VEGFA
hsa04015 Rap1 signaling pathway 9.43 × 10−5 MAPK1, AKT1, IGF1, INS, VEGFA
hsa04014 Ras signaling pathway 1.26 × 10−4 MAPK1, AKT1, IGF1, INS, VEGFA
hsa04914 Progesterone-mediated oocyte maturation 1.55 × 10−4 MAPK1, AKT1, IGF1, INS
hsa05215 Prostate cancer 1.61 × 10−4 MAPK1, AKT1, IGF1, INS
hsa05142 Chagas disease (American trypanosomiasis) 2.64 × 10−4 IL6, MAPK1, AKT1, TNF
hsa04620 Toll-like receptor signaling pathway 2.79 × 10−4 IL6, MAPK1, AKT1, TNF
hsa04931 Insulin resistance 2.95 × 10−4 IL6, AKT1, TNF, INS
hsa04932 Non-alcoholic fatty liver disease 7.90 × 10−4 IL6, AKT1, TNF, INS
hsa04960 Aldosterone-regulated sodium reabsorption 1.10 × 10−3 MAPK1, IGF1, INS
hsa05164 Influenza A 1.19 × 10−3 IL6, MAPK1, AKT1, TNF
Figure 7 Bubble diagram of KEGG pathway enrichment analysis.
Figure 7

Bubble diagram of KEGG pathway enrichment analysis.

Figure 8 Metabolic pathway map of FoxO signaling pathway.
Figure 8

Metabolic pathway map of FoxO signaling pathway.

3.5 Composition-target-pathway network

Component-target-pathway network (Figure 9) demonstrated the relationship between effective components, related protein targets, and action pathways. The network comprised 50 nodes and 106 edges, including 11 core active components, 223 targets, and 20 KEGG pathways. Calculated by Degree value (the connectivity between nodes), the top three main components were genistein (Degree = 96), daidzein (Degree = 70), and puerarin (Degree = 55).

Figure 9 “Component-target-pathway” network diagram.
Figure 9

“Component-target-pathway” network diagram.

3.6 Molecular docking results

Molecular docking was employed to verify the correlation between Radix puerariae and DN. According to the Degree value, the top three active ingredients were selected, including genistein, daidzein, and puerarin. Then, Molecular docking was performed between the selected components and six core targets. All the molecular docking binding energy between receptors and ligands were drawn into heatmap as shown in Figure 10(a). The result showed that the binding energies were less than 5 kcal/mol, indicating that the molecular components of Radix puerariae had a strong affinity for the six hub targets. The 2D structure display was screened as shown in Figure 10(b), in which hydrogen bonds were connected by green dashed lines between atoms, and the hydrophobic interaction was represented by red arcs.

Figure 10 Validation of molecular docking. (a) Molecule docking heat map of the key pharmacodynamic molecule-key target. (b) Molecular docking diagram of key ingredient and key target.
Figure 10

Validation of molecular docking. (a) Molecule docking heat map of the key pharmacodynamic molecule-key target. (b) Molecular docking diagram of key ingredient and key target.

3.7 Radix puerariae effected on renal histopathology of DN rats

Renal tissue sections were stained with HE, PASM, and Masson, respectively. The renal structure of normal rats was clean and morphologically fine, the glomerular mesangial cells and matrix appeared normal. Also, glomerular basement membrane (GBM) appeared normal, and there was no proliferation of fibrous tissue. In the DN group, the renal cortex exhibited various stages of glomerulosclerosis and tubular damage, including glomerular inherent cell hypertrophy, GBM thickening, mesangial matrix deposition, and vacuolar degeneration of tubular epithelial cells. Radix puerariae-treated kidney sections demonstrated intact glomerulus and Bowman’s space in comparison to the DN group. Several lumens were observed within the thin glomerulus loops. Also, mesangial expansion and tubulointerstitial injury were partially ameliorated (Figure 11(a)).

Figure 11 Radix puerariae improved the pathological damage and suppressed the oxidative stress in kidney. (a) HE, Masson, and PASM stained at 200× magnification, respectively; (b) the levels of AKT1, IGF1, IL-6, INS, TNF, and VEGFA by RT-PCR in kidney tissues; (c) western blot expressions of p-AKT, AKT, p-FoxO1, and FoxO1 and the ratio of p-AKT to AKT and p-FoxO1 to FoxO1. Data are presented as the mean value ± standard deviation. **P < 0.01 compared with the control group; ## P < 0.01 compared with the DN group. DN, diabetic nephropathy; RP, Radix puerariae.
Figure 11

Radix puerariae improved the pathological damage and suppressed the oxidative stress in kidney. (a) HE, Masson, and PASM stained at 200× magnification, respectively; (b) the levels of AKT1, IGF1, IL-6, INS, TNF, and VEGFA by RT-PCR in kidney tissues; (c) western blot expressions of p-AKT, AKT, p-FoxO1, and FoxO1 and the ratio of p-AKT to AKT and p-FoxO1 to FoxO1. Data are presented as the mean value ± standard deviation. **P < 0.01 compared with the control group; ## P < 0.01 compared with the DN group. DN, diabetic nephropathy; RP, Radix puerariae.

3.8 Radix puerariae alleviated oxidative stress in DN rats

The oxidative stress factor levels were measured to establish whether Radix puerariae could attenuate the oxidative stress response in DN rats. RT-PCR showed that, compared with the control group, the levels of AKT1, IL-6, and INS in the DN group were higher; the transcriptional levels of AKT1, IL-6, and INS were lower in the group that was given Radix puerariae than in the DN group (Figure 11(b)).

3.9 Radix puerariae suppressed the FoxO1 signal pathway

The FoxO1 pathways in kidney tissues were studied in order to discover possible mechanisms by which Radix puerariae protects the renal system. Western blotting was performed in order to determine the protein expression of p-AKT, AKT, p-FoxO1, and FoxO1. The ratios of p-Akt/Akt and p-FoxO1/FoxO1 were utilized to show the phosphorylation of Akt and FoxO1, respectively. AKT and FoxO1 phosphorylation ratios were higher in the DN group than in the control group, as shown in Figure 11(c). Compared with those in the DN group, decreased phosphorylated AKT and FoxO1 ratios were detected in the Radix puerariae-treated group.

4 Discussion

DN poses a significant risk to the health and well-being of diabetic patients. Although ACEI/ARB drugs have been widely used, there is an increase in the number of people developing ESRD [23]. Consequently, new drugs are necessary for the treatment of DN. In recent years, many researchers have found that Radix puerariae has anti-DN efficacy and is mainly used to reduce oxidative stress, change kidney autophagy, and anti-cell apoptosis. However, most studies explored a single component or single pathway [16,24,25]. Traditional Chinese medicine has a multi-component, multi-target mechanism and regulates multiple signaling pathways. It is difficult to clarify the systematic and synergistic effect of Radix puerariae against DN from a single aspect of research. Therefore, with the help of a network pharmacological analysis platform, our study systematically and comprehensively reveals the relationship between the effective main constituents, targets, and pathways.

Our study focuses on the anti-DN mechanism of Radix puerariae, the effective active ingredients and its corresponding targets. Previous studies have found that puerarin, the main active ingredient of Radix puerariae, can significantly improve blood glucose, proteinuria, renal function, hemodynamic status, blood lipids, blood pressure, and other indicators in patients with DN [26]. In addition to puerarin, this study found that genistein and daidzein were also related to multiple key targets of DN, revealing that these components also play a key role in treating DN, which needs to be further verified in the follow-up studies.

Comprehensive analysis of key targets, GO, KEGG enrichment, and molecular docking results have shown that Radix puerariae may regulate the HIF-1 signaling pathway, TNF signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and VEGF signaling pathway by affecting IL-6, INS, TNF, AKT1, VEGFA, and IGF1, regulates renal microcirculation and anti-podocyte apoptosis, protecting vascular endothelial cells, changing renal autophagy status, and reducing oxidative stress, thus playing a role in the treatment of DN.

According to several studies, IL-6 levels are closely related to the development of DN [27–29]. As a multifunctional cytokine, it activates the PI3K-AKT signal pathway. In vitro investigations have demonstrated that IL-6 trans-signaling triggers the release of monocyte chemoattractant protein-1 from human vascular endothelial cells. Furthermore, this process requires simultaneous activation of PI3K/AKT pathways. With the decrease in IL-6 level, the down-regulation of AKT expression and vascular endothelial injury lessened. It is confirmed that inhibition of the PI3K-AKT signal pathway can protect blood vessels and prevent vascular complications of DN [30]. Wu et al. [27] established a rat model of DN with the aim to evaluate the role of IL-6 receptor antibodies in DN. In the treatment group, albuminuria and glomerular mesangial matrix accumulation were reduced, proving that IL-6 is associated with inflammatory reaction and oxidative stress of DN. The above research works support that IL-6 is a key target for anti-DN.

Islet β cells secrete the only hypoglycemic hormone in the body. INS mutation/variation affects insulin secretion, which contributes to the occurrence and development of diabetes [31]. In addition, INS is a key target in the PI3K-Akt-mTOR signaling pathway. The PI3K-Akt-mTOR signaling pathway plays a key role in mediating cell apoptosis, promoting cell differentiation and survival, and contributes to the onset and progression of DN by inhibiting autophagy, promoting inflammation, and aggravating oxidative stress [32,33]. Therefore, the effective active components of Radix puerariae may inhibit the above signal pathways, promoting mTOR-mediated autophagy, resisting podocyte apoptosis, and reducing renal interstitial fibrosis, thus exerting the efficacy of treating DN.

Akt is one of the most important proteins in the downstream signal pathway of the PI3K/Akt/FoxO1 pathway, which is a key insulin signal molecule and has a significant regulatory role in glucose and lipid metabolism [34]. The activated form of AKT can regulate and control glucose and lipid metabolism by regulating GLUT-4, GSK-3β, Fox O1, and mTOR activities [35], thus participating in the occurrence and development of DN and drug therapy.

Fox transcription factors can be found in organisms from yeast to humans, as well as in kidneys, where they are widely expressed. Among them, Fox O1 is widely expressed in a variety of renal parenchyma cells, such as podocytes and mesangial cells, and plays an essential role in the pathogenesis of various renal injuries [36]. Several studies [37–39] have shown that PI3K/Akt can directly phosphorylate Fox O1, hence inhibiting Fox O1 activity. The decrease in the expression level of Fox O1 will lead to the decrease in antioxidant enzymes, the reduction in autophagy level, the increase in blood glucose level, and the disorder of lipid metabolism, thereby accelerating the progress of DN. Relevant studies [40,41] suggest that in the diabetes model, the reduction in Fox O1 phosphorylation contribute to the improvement of renal function, while the high expression of Fox O1 can reduce the apoptosis induced by high glucose through activating PTEN-Induced putative kinase (PINK1), improve the autophagy level and cell vitality, effectively alleviate renal injury, and inhibit the process of renal fibrosis.

In this study, we established a DN rat model and preliminarily explored the mechanism of Radix puerariae in treating DN by observing the pathological changes in kidney tissue, renal tissue cytokines, and the key proteins in the FoxO1 signal pathway. Histopathological characteristics of DN rats’ kidneys included glomerular inherent cell hypertrophy, GBM thickening, mesangial matrix deposition, and vacuolar degeneration of tubular epithelial cells. Radix puerariae treatment partially improved glomerular hypertrophy, mesangial matrix expansion, and tubulointerstitial injury. PASM and Masson’s trichrome showed a moderate expansion of the mesangial matrix, and extracellular matrix deposition in both glomeruli and tubulointerstitium in the DN group, treatment with Radix puerariae significantly inhibited these histologic injuries. AKT1, IL-6, and INS were the core targets screened by network pharmacology. This study has shown that the expression of AKT1, IL-6, and INS mRNA in the DN group was significantly higher than those in the control group. Radix puerariae down-regulated the expression level of AKT1, IL-6, and INS and showed a significant effect on alleviating the progress of DN by reducing oxidative stress injury. Furthermore, FoxO1 has been associated with the development of DN and has been shown to play a role in its development. In our study, we found that the FoxO1 pathway was upregulated in the DN group, as we found overexpression of p-Akt and p-FoxO1 in the kidney, suggesting that high glucose may increase the phosphorylation of FoxO1 through activating the FoxO1 pathway. However, the FoxO1 pathway was downregulated after Radix puerariae treatment. The activity of FoxO1 increased, thus slowing down the development of DN.

5 Conclusion

In conclusion, we used the network pharmacological approach to investigate the main target proteins of Radix puerariae compounds that displayed anti-DN activity by constructing a “component-target-disease” network and validated our findings in animal models. The results of our study indicated that 12 compounds, including genistein, daidzein, puerarin, and so on, had the potential to be used as therapeutic agents in the treatment of DN. The interaction of these bioactive compounds with AKT1, IL-6, INS, and other enzymes was predicted. Additionally, biological process and pathway enrichment analysis of the target proteins of Radix puerariae strengthened our understanding of the mechanism of action of the active ingredients. This study provides valuable insight into the mechanism by which Radix puerariae inhibits the progression of DN by interfering with the FOX1 signaling pathway. Further studies will be conducted to investigate the possible therapeutic benefits and mechanisms of Radix puerariae and combination therapies for the treatment of DN.

  1. Funding information: This study was supported by the Educational Department in Jiangxi Province under the Grants [GJJ201819 and GJJ211805], Health Commission of Jiangxi Provincial under the Grant [202212007], Jiangxi Provincial Administration of Traditional Chinese Medicine under the grant [2022A137], Beijing Medical and Health Foundation under the Grant [TYU046B], and Beijing Medical Award Foundation under the Grant [_YXJL-2022-0734-0294].

  2. Author contributions: Cheng Li: data curation, formal analysis, development or design of methodology, validation, and writing – original draft. Hongli Jiang: project administration. Jingchun Yao: creation of models, data/evidence collection, and visualization. Xulong Chen: funding acquisition, resources, writing – review and editing. PuXun Tian: conceptualization and supervision.

  3. Conflict of interest: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

  4. Ethical approval: This study was approved by the Medical Ethics Committee of Jiujiang University Affiliated Hospital, Jiujiang, China (protocol approval number: jjuhmer-a-2022-02; approval date: 15 April 2022).

  5. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-02-13
Revised: 2023-03-19
Accepted: 2023-03-20
Published Online: 2023-04-27

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
  185. Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes
  186. Evaluation and chemical characterization of bioactive secondary metabolites from endophytic fungi associated with the ethnomedicinal plant Bergenia ciliata
  187. Enhancing photovoltaic efficiency with SQI-Br and SQI-I sensitizers: A comparative analysis
  188. Nanostructured p-PbS/p-CuO sulfide/oxide bilayer heterojunction as a promising photoelectrode for hydrogen gas generation
https://doi.org/10.1515/chem-2022-0311
Schlagwörter für diesen Artikel
Radix puerariae; diabetic nephropathy; network pharmacology; molecular docking; FoxO1 signaling pathway
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  2. Regular Articles
  3. A network-based correlation research between element electronegativity and node importance
  4. Pomegranate attenuates kidney injury in cyclosporine-induced nephrotoxicity in rats by suppressing oxidative stress
  5. Ab initio study of fundamental properties of XInO3 (X = K, Rb, Cs) perovskites
  6. Responses of feldspathic sandstone and sand-reconstituted soil C and N to freeze–thaw cycles
  7. Robust fractional control based on high gain observers design (RNFC) for a Spirulina maxima culture interfaced with an advanced oxidation process
  8. Study on arsenic speciation and redistribution mechanism in Lonicera japonica plants via synchrotron techniques
  9. Optimization of machining Nilo 36 superalloy parameters in turning operation
  10. Vacuum impregnation pre-treatment: A novel method for incorporating mono- and divalent cations into potato strips to reduce the acrylamide formation in French fries
  11. Characterization of effective constituents in Acanthopanax senticosus fruit for blood deficiency syndrome based on the chinmedomics strategy
  12. Comparative analysis of the metabolites in Pinellia ternata from two producing regions using ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry
  13. The assessment of environmental parameter along the desalination plants in the Kingdom of Saudi Arabia
  14. Effects of harpin and carbendazim on antioxidant accumulation in young jujube leaves
  15. The effects of in ovo injected with sodium borate on hatching performance and small intestine morphology in broiler chicks
  16. Optimization of cutting forces and surface roughness via ANOVA and grey relational analysis in machining of In718
  17. Essential oils of Origanum compactum Benth: Chemical characterization, in vitro, in silico, antioxidant, and antibacterial activities
  18. Translocation of tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses towards improvement of gamma-ray attenuation features in high-density glass shields
  19. Mechanical properties, elastic moduli, and gamma ray attenuation competencies of some TeO2–WO3–GdF3 glasses: Tailoring WO3–GdF3 substitution toward optimum behavioral state range
  20. Comparison between the CIDR or sponge with hormone injection to induce estrus synchronization for twining and sex preselection in Naimi sheep
  21. Exergetic performance analyses of three different cogeneration plants
  22. Psoralea corylifolia (babchi) seeds enhance proliferation of normal human cultured melanocytes: GC–MS profiling and biological investigation
  23. A novel electrochemical micro-titration method for quantitative evaluation of the DPPH free radical scavenging capacity of caffeic acid
  24. Comparative study between supported bimetallic catalysts for nitrate remediation in water
  25. Persicaline, an alkaloid from Salvadora persica, inhibits proliferation and induces apoptosis and cell-cycle arrest in MCF-7 cells
  26. Determination of nicotine content in locally produced smokeless tobacco (Shammah) samples from Jazan region of Saudi Arabia using a convenient HPLC-MS/MS method
  27. Changes in oxidative stress markers in pediatric burn injury over a 1-week period
  28. Integrated geophysical techniques applied for petroleum basins structural characterization in the central part of the Western Desert, Egypt
  29. The impact of chemical modifications on gamma-ray attenuation properties of some WO3-reinforced tellurite glasses
  30. Microwave and Cs+-assisted chemo selective reaction protocol for synthesizing 2-styryl quinoline biorelevant molecules
  31. Structural, physical, and radiation absorption properties of a significant nuclear power plant component: A comparison between REX-734 and 316L SS austenitic stainless steels
  32. Effect of Moringa oleifera on serum YKL-40 level: In vivo rat periodontitis model
  33. Investigating the impact of CO2 emissions on the COVID-19 pandemic by generalized linear mixed model approach with inverse Gaussian and gamma distributions
  34. Influence of WO3 content on gamma rays attenuation characteristics of phosphate glasses at low energy range
  35. Study on CO2 absorption performance of ternary DES formed based on DEA as promoting factor
  36. Performance analyses of detonation engine cogeneration cycles
  37. Sterols from Centaurea pumilio L. with cell proliferative activity: In vitro and in silico studies
  38. Untargeted metabolomics revealing changes in aroma substances in flue-cured tobacco
  39. Effect of pumpkin enriched with calcium lactate on iron status in an animal model of postmenopausal osteoporosis
  40. Energy consumption, mechanical and metallographic properties of cryogenically treated tool steels
  41. Optimization of ultra-high pressure-assisted extraction of total phenols from Eucommia ulmoides leaves by response surface methodology
  42. Harpin enhances antioxidant nutrient accumulation and decreases enzymatic browning in stored soybean sprouts
  43. Physicochemical and biological properties of carvacrol
  44. Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation
  45. Anti-Alzheimer, antioxidants, glucose-6-phosphate dehydrogenase effects of Taverniera glabra mediated ZnO and Fe2O3 nanoparticles in alloxan-induced diabetic rats
  46. Experimental study on photocatalytic CO2 reduction performance of ZnS/CdS-TiO2 nanotube array thin films
  47. Epoxy-reinforced heavy metal oxides for gamma ray shielding purposes
  48. Black mulberry (Morus nigra L.) fruits: As a medicinal plant rich in human health-promoting compounds
  49. Promising antioxidant and antimicrobial effects of essential oils extracted from fruits of Juniperus thurifera: In vitro and in silico investigations
  50. Chloramine-T-induced oxidation of Rizatriptan Benzoate: An integral chemical and spectroscopic study of products, mechanisms and kinetics
  51. Study on antioxidant and antimicrobial potential of chemically profiled essential oils extracted from Juniperus phoenicea (L.) by use of in vitro and in silico approaches
  52. Screening and characterization of fungal taxol-producing endophytic fungi for evaluation of antimicrobial and anticancer activities
  53. Mineral composition, principal polyphenolic components, and evaluation of the anti-inflammatory, analgesic, and antioxidant properties of Cytisus villosus Pourr leaf extracts
  54. In vitro antiproliferative efficacy of Annona muricata seed and fruit extracts on several cancer cell lines
  55. An experimental study for chemical characterization of artificial anterior cruciate ligament with coated chitosan as biomaterial
  56. Prevalence of residual risks of the transfusion-transmitted infections in Riyadh hospitals: A two-year retrospective study
  57. Computational and experimental investigation of antibacterial and antifungal properties of Nicotiana tabacum extracts
  58. Reinforcement of cementitious mortars with hemp fibers and shives
  59. X-ray shielding properties of bismuth-borate glass doped with rare earth ions
  60. Green supported silver nanoparticles over modified reduced graphene oxide: Investigation of its antioxidant and anti-ovarian cancer effects
  61. Orthogonal synthesis of a versatile building block for dual functionalization of targeting vectors
  62. Thymbra spicata leaf extract driven biogenic synthesis of Au/Fe3O4 nanocomposite and its bio-application in the treatment of different types of leukemia
  63. The role of Ag2O incorporation in nuclear radiation shielding behaviors of the Li2O–Pb3O4–SiO2 glass system: A multi-step characterization study
  64. A stimuli-responsive in situ spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds
  65. Assessment of the impact of γ-irradiation on the piperine content and microbial quality of black pepper
  66. Antioxidant, sensory, and functional properties of low-alcoholic IPA beer with Pinus sylvestris L. shoots addition fermented using unconventional yeast
  67. Screening and optimization of extracellular pectinase produced by Bacillus thuringiensis SH7
  68. Determination of polyphenols in Chinese jujube using ultra-performance liquid chromatography–mass spectrometry
  69. Synergistic effects of harpin and NaCl in determining soybean sprout quality under non-sterile conditions
  70. Field evaluation of different eco-friendly alternative control methods against Panonychus citri [Acari: Tetranychidae] spider mite and its predators in citrus orchards
  71. Exploring the antimicrobial potential of biologically synthesized zero valent iron nanoparticles
  72. NaCl regulates goldfish growth and survival at three food supply levels under hypoxia
  73. An exploration of the physical, optical, mechanical, and radiation shielding properties of PbO–MgO–ZnO–B2O3 glasses
  74. A novel statistical modeling of air pollution and the COVID-19 pandemic mortality data by Poisson, geometric, and negative binomial regression models with fixed and random effects
  75. Treatment activity of the injectable hydrogels loaded with dexamethasone In(iii) complex on glioma by inhibiting the VEGF signaling pathway
  76. An alternative approach for the excess lifetime cancer risk and prediction of radiological parameters
  77. Panax ginseng leaf aqueous extract mediated green synthesis of AgNPs under ultrasound condition and investigation of its anti-lung adenocarcinoma effects
  78. Study of hydrolysis and production of instant ginger (Zingiber officinale) tea
  79. Novel green synthesis of zinc oxide nanoparticles using Salvia rosmarinus extract for treatment of human lung cancer
  80. Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-α levels in pregnant women with gestational diabetes mellitus
  81. Antidiabetic, antioxidant and cytotoxicity activities of ortho- and para-substituted Schiff bases derived from metformin hydrochloride: Validation by molecular docking and in silico ADME studies
  82. Antioxidant, antidiabetic, antiglaucoma, and anticholinergic effects of Tayfi grape (Vitis vinifera): A phytochemical screening by LC-MS/MS analysis
  83. Identification of genetic polymorphisms in the stearoyl CoA desaturase gene and its association with milk quality traits in Najdi sheep
  84. Cold-acclimation effect on cadmium absorption and biosynthesis of polyphenolics, and free proline and photosynthetic pigments in Spirogyra aequinoctialis
  85. Analysis of secondary metabolites in Xinjiang Morus nigra leaves using different extraction methods with UPLC-Q/TOF-MS/MS technology
  86. Nanoarchitectonics and performance evaluation of a Fe3O4-stabilized Pickering emulsion-type differential pressure plugging agent
  87. Investigating pyrolysis characteristics of Shengdong coal through Py-GC/MS
  88. Extraction, phytochemical characterization, and antifungal activity of Salvia rosmarinus extract
  89. Introducing a novel and natural antibiotic for the treatment of oral pathogens: Abelmoschus esculentus green-formulated silver nanoparticles
  90. Optimization of gallic acid-enriched ultrasonic-assisted extraction from mango peels
  91. Effect of gamma rays irradiation in the structure, optical, and electrical properties of samarium doped bismuth titanate ceramics
  92. Combinatory in silico investigation for potential inhibitors from Curcuma sahuynhensis Škorničk. & N.S. Lý volatile phytoconstituents against influenza A hemagglutinin, SARS-CoV-2 main protease, and Omicron-variant spike protein
  93. Physical, mechanical, and gamma ray shielding properties of the Bi2O3–BaO–B2O3–ZnO–As2O3–MgO–Na2O glass system
  94. Twofold interpenetrated 3D Cd(ii) complex: Crystal structure and luminescent property
  95. Study on the microstructure and soil quality variation of composite soil with soft rock and sand
  96. Ancient spring waters still emerging and accessible in the Roman Forum area: Chemical–physical and microbiological characterization
  97. Extraction and characterization of type I collagen from scales of Mexican Biajaiba fish
  98. Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening
  99. Prefatory in silico studies and in vitro insecticidal effect of Nigella sativa (L.) essential oil and its active compound (carvacrol) against the Callosobruchus maculatus adults (Fab), a major pest of chickpea
  100. Polymerized methyl imidazole silver bromide (CH3C6H5AgBr)6: Synthesis, crystal structures, and catalytic activity
  101. Using calcined waste fish bones as a green solid catalyst for biodiesel production from date seed oil
  102. Influence of the addition of WO3 on TeO2–Na2O glass systems in view of the feature of mechanical, optical, and photon attenuation
  103. Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway
  104. GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities
  105. Green synthesis, chemical characterization, and antioxidant and anti-colorectal cancer effects of vanadium nanoparticles
  106. Determination of caffeine content in coffee drinks prepared in some coffee shops in the local market in Jeddah City, Saudi Arabia
  107. A new 3D supramolecular Cu(ii) framework: Crystal structure and photocatalytic characteristics
  108. Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
  109. Important application value of injectable hydrogels loaded with omeprazole Schiff base complex in the treatment of pancreatitis
  110. Color tunable benzothiadiazole-based small molecules for lightening applications
  111. Investigation of structural, dielectric, impedance, and mechanical properties of hydroxyapatite-modified barium titanate composites for biomedical applications
  112. Metal gel particles loaded with epidermal cell growth factor promote skin wound repair mechanism by regulating miRNA
  113. In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent
  114. Alteration in the molecular structure of the adenine base exposed to gamma irradiation: An ESR study
  115. Comprehensive study of optical, thermal, and gamma-ray shielding properties of Bi2O3–ZnO–PbO–B2O3 glasses
  116. Lewis acids as co-catalysts in Pd-based catalyzed systems of the octene-1 hydroethoxycarbonylation reaction
  117. Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes
  118. Protective properties of AgNPs green-synthesized by Abelmoschus esculentus on retinal damage on the virtue of its anti-inflammatory and antioxidant effects in diabetic rat
  119. Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis
  120. Treatment of gastric cancer by green mediated silver nanoparticles using Pistacia atlantica bark aqueous extract
  121. Preparation of newly developed porcelain ceramics containing WO3 nanoparticles for radiation shielding applications
  122. Utilization of computational methods for the identification of new natural inhibitors of human neutrophil elastase in inflammation therapy
  123. Some anticancer agents as effective glutathione S-transferase (GST) inhibitors
  124. Clay-based bricks’ rich illite mineral for gamma-ray shielding applications: An experimental evaluation of the effect of pressure rates on gamma-ray attenuation parameters
  125. Stability kinetics of orevactaene pigments produced by Epicoccum nigrum in solid-state fermentation
  126. Treatment of denture stomatitis using iron nanoparticles green-synthesized by Silybum marianum extract
  127. Characterization and antioxidant potential of white mustard (Brassica hirta) leaf extract and stabilization of sunflower oil
  128. Characteristics of Langmuir monomolecular monolayers formed by the novel oil blends
  129. Strategies for optimizing the single GdSrFeO4 phase synthesis
  130. Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
  131. Unraveling the therapeutic potential of Bombax ceiba roots: A comprehensive study of chemical composition, heavy metal content, antibacterial activity, and in silico analysis
  132. Green synthesis of AgNPs using plant extract and investigation of its anti-human colorectal cancer application
  133. The adsorption of naproxen on adsorbents obtained from pepper stalk extract by green synthesis
  134. Treatment of gastric cancer by silver nanoparticles encapsulated by chitosan polymers mediated by Pistacia atlantica extract under ultrasound condition
  135. In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile
  136. Wear and corrosion behavior of TiC and WC coatings deposited on high-speed steels by electro-spark deposition
  137. Therapeutic effects of green-formulated gold nanoparticles by Origanum majorana on spinal cord injury in rats
  138. Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens
  139. Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles
  140. Review Articles
  141. Role and mechanism of fruit waste polyphenols in diabetes management
  142. A comprehensive review of non-alkaloidal metabolites from the subfamily Amaryllidoideae (Amaryllidaceae)
  143. Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus
  144. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications
  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
  185. Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes
  186. Evaluation and chemical characterization of bioactive secondary metabolites from endophytic fungi associated with the ethnomedicinal plant Bergenia ciliata
  187. Enhancing photovoltaic efficiency with SQI-Br and SQI-I sensitizers: A comparative analysis
  188. Nanostructured p-PbS/p-CuO sulfide/oxide bilayer heterojunction as a promising photoelectrode for hydrogen gas generation
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Heruntergeladen am 29.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/chem-2022-0311/html
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