scholarly journals Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Li Ou ◽  
Wenqian Kang ◽  
Ziyi Liang ◽  
Feng Gao ◽  
Taiwei Dong ◽  
...  

Abstract Background Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology. Methods The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments. Results According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density. Conclusion This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.

2021 ◽  
Author(s):  
Li Ou ◽  
Wenqian Kang ◽  
Ziyi Liang ◽  
Feng Gao ◽  
Taiwei Dong ◽  
...  

Abstract Background: Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate anti-osteoporosis mechanisms of RRP through network pharmacology.Methods: The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were randomly verified through pharmacological experiments. Results: According to topological analysis results, AKT1, MAPK1, ESR1, SRC, and MMP9 are key genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including Estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway, etc. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, ESR1 and SRC-1 mRNA in bone tissue to promote bone formation. Conclusion: This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis, and provided new ideas and basis for its clinical application and experimental research.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Haoxian Wang ◽  
Jihong Zhang ◽  
Qinqin Zhu ◽  
Xianyun Fu ◽  
Chenjie Li

Aim. This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. Methods. The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. Results. A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells’ estrogen resistance via GPER/EGFR signaling pathway. Conclusion. The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.


2020 ◽  
Author(s):  
Xiang-Jing Chen ◽  
Ran Zhang ◽  
Ren-Zhong Wang ◽  
Cheng-Fang Yao

Abstract Background: Traditional Chinese Medicine has demonstrated increasingly unique advantages in the treatment of lung cancer. Through literature review, it was found out that Platycodon grandiflorum had immunomodulatory and anti-inflammatory effects, and it had a special targeting effect on the lung. Purpose:In order to determine the molecular mechanism of Platycodon grandiflorum in lung cancer treatment. Network pharmacology theory was used to do a systematic study.Methods: The active compounds of Platycodon grandiflorum were screened from TCMSP database. Then, compounds targets were predicted with the assistance of Swiss Target Prediction and STITCH. The targets of lung cancer were screened form TTD and DisGeNET database. The common targets of compounds and lung cancer were screened out for following analysis. A Protein-Protein Interaction (PPI) Network was constructed by STRING. Subsequent to topological analysis, the hub targets were screened out for KEGG pathway and GO Enrichment. Molecular docking by AutoVina was performed to investigate the binding ability between the hub targets and compounds. Results: There were 4 active compounds screened out, including Acacetin, Spinasterol, cis-Dihydroquercetin and Luteolin. There were 80 targets screened as the common target of compounds and lung cancer. After topological analysis TP53, AKT1, VEGFA, CASP3, IL6, EGFR and MAPK1 were identified as hub targets. The 7 hub targets might be involved in 81 biological annotation and in the regulation of 23 pathways to intervene lung cancer. The main functional annotation was negative regulation of apoptotic process. Almost all of the pathways were directly or indirectly associated with the PI3K-Akt signal pathway and MAPK signal pathway. According to Affinity score of molecular docking the best binding protein for Luteolin was EGFR, and the best binding protein for Acacetin was CASP3. This meant that the Platycodon grandiflorum was easier to combine these two targets than other targets.Conclusion: Our study affirmed the effectiveness of Platycodon grandiflorum in treatment of lung cancer from molecular level. And we found that EGFR and CASP3 were the most likely targets for the direct action of Platycodon grandiflorum. The most important pathways that Platycodon grandiflori might interfere with were PI3K-Akt signaling pathway and MAPK signaling pathway.


2020 ◽  
Author(s):  
xia liu ◽  
Mingchun Huang ◽  
Chen Yang ◽  
Qin Wang ◽  
Mei Zhang

Abstract Introduction: As a traditional Chinese medicine (TCM), Curculigo orchioides Gaertn. (Xianmao) has been widely used to treat bone-related diseases. However, the active components of this TCM, and the specific mechanisms by which it exerts effect, have yet to be elucidated. To identify potential targets for orcinol glucoside (OG), an active constituent of C. orchioides, during the treatment of osteoporosis (OP) by adopting a network pharmacology approach. Methods: First, we mined the Similarity ensemble approach (SEA), SwissTargetPrediction, DisGeNET, and Genecards databases were mined for data related to the prediction of OG- and OP-related targets. Next, we identified the common targets for OG and OP, and then used STRING software to create a protein-protein interaction (PPI) network. Then, we used topological analysis to identify which of the common targets were most significant. Then, we used the common significant targets and g:profiler to perform gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway enrichment analysis. Finally, we used molecular docking to predict the targets of OG that were most relevant to the treatment of OP and investigated the potential pharmacological mechanisms that might be involved. Results: In total, 130 potential targets of OG, and 4582 targets relevant to OP, were subjected to network analysis. There were 73 common targets; these identified the principal pathways linked to OP. In addition, topological analysis identified 14 key targets. Most of the predicted targets played crucial roles in the PI3K-AKT signaling pathway. Molecular docking identified ten core targets (VEGFA, IL6, EGFR, MAPK1, HRAS, CCND1, FGF2, IL2, MCL1 and CDK4), thus indicating that OG may promote osteoblast proliferation and differentiation by accelerating progression of the cell cycle.Conclusions: This research provides a theoretical base for identifying the specific potential mechanisms of OG in treatment of OP.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jiexin Wang ◽  
Haiqing Chu ◽  
Hangying Li ◽  
Wenqian Yang ◽  
Yu Zhao ◽  
...  

Erjing prescription (EJP) was an ancient formula that was recorded in the General Medical Collection of Royal Benevolence of the Song Dynasty. It has been frequently used to treat type 2 diabetes mellitus (T2DM) in the long history of China. The formula consists of Lycium barbarum L. and Polygonatum sibiricum F. Delaroche with a ratio of 1 : 1. This study aimed to identify the potential effects and mechanisms of EJP treatment T2DM. The target proteins and possible pathways of EJP in T2DM treatment were investigated by the approach of network pharmacology and real-time PCR (RT-PCR). 99 diabetes-related proteins were regulated by 56 bioactive constituents in EJP in 26 signal pathways by Cytoscape determination. According to GO analysis, 606 genes entries have been enriched. The PPI network suggested that AKT1, EGF, EGFR, MAPK1, and GSK3β proteins were core genes. Among the 26 signal pathways, the PI3K-AKT signal pathway was tested by the RT-PCR. The expression level of PI3K p85, AKT1, GSK3β, and Myc mRNA of this pathway was regulated by EJP. The study based on network pharmacology and RT-PCR analysis revealed that the blood sugar level was regulated by EJP via regulating the PI3K-AKT signal pathway. Plenty of new treatment methods for T2DM using EJP were provided by network pharmacology analysis.


2022 ◽  
Vol 12 ◽  
Author(s):  
Jinlong Zhao ◽  
Fangzheng Lin ◽  
Guihong Liang ◽  
Yanhong Han ◽  
Nanjun Xu ◽  
...  

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.


2020 ◽  
Vol 14 (4) ◽  
pp. 467-475
Author(s):  
Chengguo Zhao ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
Meifang Yin ◽  
Shuzhi Qin

This study explored the mechanism of paeoniflorin (PF) against atherosclerosis (AS) at the molecular level using network pharmacology and molecular docking. The targets of PF and disease targets related to AS were obtained through literature mining and database search, the PPI network diagram was drawn, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the PF structure was docked with core target. In the results, 130 common target proteins of PF and AS were obtained. GO enrichment analysis found 1071 items related to biological processes, mainly related to metabolism, protein modification, regulation of cell activity, regulation of macromolecule synthesis, etc. There were 107 items related to molecular functions, mainly related to cyclic compounds, ions, nucleotides, and ribose Combine etc. KEGG analysis revealed 79 pathways, mainly Pathways in cancer, PI3K-Akt signalling pathway, Proteoglycans in cancer, Ras signalling pathway, FoxO signalling pathway, etc. The molecular docking results showed that PF had good binding activity with the screened target. In conclusion, this study indicated that PF treatment of AS involves multiple direct or indirect targets and signal pathways, providing a reference for further research on the mechanism of PF treatment of AS.


2021 ◽  
Author(s):  
Yaling Hu ◽  
Shuang Liu ◽  
Wenyuan Liu ◽  
Ziyuan Zhang ◽  
Yuxiang Liu ◽  
...  

Abstract Background : Using network pharmacology and molecular docking technology to explore the mechanism of Yishen capsules in the treatment of diabetic nephropathy. Methods: Active components of Yishen Capsules were obtained using database such as TCMSP and TCMID, and diabetic nephropathy targets were obtained from databases such as Gencards, OMIM, DisGeNET. A network of "Yishen Capsule Components-Diabetic Nephropathy Targets-Pathways" was constructed by analyzing data above to screening out core targets for molecular docking verification. Finally, a rat model of diabetic nephropathy was generated, and renal tubular epithelial cells were extracted and cultured under high glucose conditions. Based on these experimental models, the key signal pathway target protein genes screened by network pharmacology were verified both in vitro and in vivo. Results: The main active components of Yishen Capsule in the treatment of diabetic nephropathy include quercetin, kaempferol, gallic acid, astragaloside IV and so on. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE signal pathway, HIF-1 signal pathway and JAK-STAT signal pathway) were included in the treatment of diabetic nephropathy of Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsules. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β were decreased. Conclusions : This study revealed the mechanism of Yishen Capsules in the treatment of diabetic nephropathy, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsules interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy. Key Words: Diabetic Nephropathy(DN); Network pharmacology; Molecular docking;HIF-1α; JAK/STAT


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Meiqi Wei ◽  
He Li ◽  
Qifang Li ◽  
Yi Qiao ◽  
Qun Ma ◽  
...  

Background. Gegen Qinlian (GGQL) decoction is a common Chinese herbal compound for the treatment of ulcerative colitis (UC). In this study, we aimed to identify its molecular target and the mechanism involved in UC treatment by network pharmacology and molecular docking. Material and Methods. The active ingredients of Puerariae, Scutellariae, Coptis, and Glycyrrhiza were screened using the TCMSP platform with drug ‐ like   properties   DL ≥ 0.18 and oral   availability   OB ≥ 30 % . To find the intersection genes and construct the TCM compound-disease regulatory network, the molecular targets were determined in the UniProt database and then compared with the UC disease differential genes with P value < 0.005 and ∣ log 2   fold   change ∣ > 1 obtained in the GEO database. The intersection genes were subjected to protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After screening the key active ingredients and target genes, the AutoDock software was used for molecular docking, and the best binding target was selected for molecular docking to verify the binding activity. Results. A total of 146 active compounds were screened, and quercetin, kaempferol, wogonin, and stigmasterol were identified as the active ingredients with the highest associated targets, and NOS2, PPARG, and MMP1 were the targets associated with the maximum number of active ingredients. Through topological analysis, 32 strongly associated proteins were found, of which EGFR, PPARG, ESR1, HSP90AA1, MYC, HSPA5, AR, AKT1, and RELA were predicted targets of the traditional Chinese medicine, and PPARG was also an intersection gene. It was speculated that these targets were the key to the use of GGQL in UC treatment. GO enrichment results showed significant enrichment of biological processes, such as oxygen levels, leukocyte migration, collagen metabolic processes, and nutritional coping. KEGG enrichment showed that genes were particularly enriched in the IL-17 signaling pathway, AGE-RAGE signaling pathway, toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transcriptional deregulation in cancer, and other pathways. Molecular docking results showed that key components in GGQL had good potential to bind to the target genes MMP3, IL1B, NOS2, HMOX1, PPARG, and PLAU. Conclusion. GGQL may play a role in the treatment of ulcerative colitis by anti-inflammation, antioxidation, and inhibition of cancer gene transcription.


2021 ◽  
Author(s):  
Shao-Xuan Liu ◽  
Feng-Juan Han ◽  
Chun-Lan Zhang ◽  
Ying Shen ◽  
Jia Li ◽  
...  

Abstract Background and objective: Li Chong Wan (Li Chong pill, LCP) origin from Yi Xue Zhong Zhong Can Xi Lu, (Records of Chinese Medicine with Reference to Western Medicine), widely used in the treatment of endometriosis (EM) in China. The purpose of this study is to investigate the intrinsic mechanisms of LCP against EM and to provide new evidence for its clinical application.Methods: Chemical compounds of LCP were screened and evaluated via retrieving public databases and literature. We also acquired their putative targets and obtained EM-related targets. The above-mentioned data were visualized as a component-target network. In addition, we use Cytoscape3.8.0 to build a protein-protein interaction network and identified hub genes and key active ingredients. Furthermore, through GO and KEGG pathway analyses, which were actualized by R3.6.1 (based on clusterProfiler, org.Hs.eg.Db, and pathview package), we obtained effective signaling pathways and biological functions. Molecular docking was used to verify binding activity between compounds and the key targets at last.Results: Finally, a total of 122 possible active targets and 47 components were screened. Identify the core network and screen out 10 main targets; GO and KEGG enrichment analysis revealed that LCP may have functions of anti-inflammatory, anti-angiogenesis, inhibition of cell proliferation, regulation of hormone secretion, etc. The effect of LCP on EM might be achieved by PI3K/Akt signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, and VEGF signaling pathway, etc. Finally, molecular docking results demonstrated that 14 components were exhibited good binding property to the key targets of EM.Conclusion: This research ocularly demonstrated the multi-component, multi-target, and multi-channel pharmacological effects for LCP in the treatments of EM and provides evidence for further clinical research and verification of the mechanism.


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