scholarly journals Network Pharmacology Study of The Mechanism of Anti-Pneumonia Action Mechanism of Gentiana Rhodantha Franch

2021 ◽  
Author(s):  
Jun Luo ◽  
Xiusheng Tang ◽  
Guotao Shu ◽  
Dongxin Tang ◽  
Jia Yu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathway ◽  
High Throughput Sequencing ◽  
Biological Information ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Sequencing Analysis ◽  
Data Set ◽  
Annotation Database ◽  
Functional Richness

Abstract Background: Serum dragon bile is a Chinese medicine used to treat pneumonia, but its mechanism of action is not clear. Meanwhile, due to the development of microarray and RNA‐sequencing technology, high-throughput sequencing analysis is being used increasingly, and it has been applied as an indispensable tool in many medical fields. Therefore, in this article, we want to employed the bioinformatics approach to explore the relevant pharmacological mechanism of dragon serum bile in the treatment of pneumonia through network pharmacology.Methods: In this paper, the active chemical composition and action target of serum dragon bile are obtained through the pharmacology database (TCMSP) of Chinese medicine system and the literature, and the data set of the intersection of active ingredient and disease target is established, and the protein interoperability network of serum gallbladder action target and pneumonia action target is analyzed by using protein interaction network (PPI). Using the Biological Information Annotation Database (DAVID) for gene ontology (GO) functional richness analysis and based on kyoto Gene and Genomics Encyclopedia (KEGG) pathogenic rich analysis, to predict the mechanism of the role of seroclon bile against pneumonia. Results: Through the network pharmacological prediction, it is shown that the main chemical components of serum dragon bile are quercetin, isoorientin, luteolin, Stigmasterol, vanillic acid, etc, all of which have anti-pneumonia effects. The anti-pneumonia effect of serum dragon bile is mainly regulated by pathways in cancer, Bradder cancer, TNF signaling pathway, Hepatitis B and Non-small cell lung cancer, among which the TNF signaling pathway is more associated with pneumonia. Conclusions: It is concluded from the network pharmacological prediction that serum dragon bile may play an anti-pneumonia role by promoting apoptosis, survival, immunity, etc. Its anti-pneumonia path is closely related to key targets IL6, FOS, CASP3 and AKT1. This study provides theoretical support for the follow-up study of the anti-pneumonia mechanism of serum gentian bile.

scholarly journals Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

2021 ◽  
Author(s):  
Dianna Liu ◽  
Shicheng Lin ◽  
Yuan Li ◽  
Tian Zhou ◽  
Kaiwen Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Network Pharmacology ◽  
Phytochemical Analysis ◽  
Sequencing Analysis ◽  
Lewis Lung ◽  
Hub Genes

Abstract BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

scholarly journals Study on the Mechanism of Lianpu Drink for the Treatment of Chronic Gastritis Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhan Zhou ◽  
Yanjun Duan ◽  
Yu Deng ◽  
Miao Wang ◽  
Chaoqun Huang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Chronic Gastritis ◽  
Mechanisms Of Action ◽  
Network Pharmacology ◽  
Biological Pathway ◽  
Disease Network ◽  
Target Disease ◽  
Compound Target

Chronic gastritis (CG) places a considerable burden on the healthcare system worldwide. Traditional Chinese Medicine (TCM) formulas characterized by multicompounds and multitargets have been acknowledged with striking effects in the treatment of CG in China’s history. Nevertheless, their accurate mechanisms of action are still ambiguous. In this study, we analyzed the effective compounds, potential targets, and related biological pathway of Lianpu Drink (LPD), a TCM formula which has been reported to have a therapeutic effect on CG, by contrasting a “compound-target-disease” network. According to the results, 92 compounds and 5762 putative targets of LPD were screened; among them, 8 compounds derived from different herbs in LPD and 30 common targets related to LPD and CG were selected as candidate compounds and precision targets, respectively. Meanwhile, the predicted common targets were verified by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and pharmacological experiments. The results demonstrated that quercetin, ephedrine, trigonelline, crocetin, and β-sitosterol were major effective compounds of LPD responsible for the CG treatment by inhibiting the activation of the JAK 2-STAT 3 signaling pathway to reduce the expressions of cyclin D1 and Bcl-2 proteins. The study provides evidence for the mechanism of understanding of LPD for the treatment of CG.

scholarly journals The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of  Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Active Components ◽  
Pathway Enrichment

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.

scholarly journals Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yangyun Wang ◽  
Wandong Yu ◽  
Chaoliang Shi ◽  
Wei Jiao ◽  
Junhong Li ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Signaling Pathway ◽  
Herbal Medicines ◽  
Mapk Signaling ◽  
Glycyrrhetinic Acid ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Chemical Components ◽  
Target Proteins ◽  
Yougui Pill

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

scholarly journals Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuefeng Zhang ◽  
Fei Yu ◽  
Jingyou Hao ◽  
Eliphaz Nsabimana ◽  
Yanru Wei ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Pathological Condition ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K–Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K–Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

scholarly journals A Network Pharmacology-Based Study on Active Ingredients of Corydalis Rhizoma on Coronary Heart Disease

2020 ◽  
Author(s):  
Ying Li ◽  
Guhang Wei ◽  
Zhenkun Zhuang ◽  
Mingtai Chen ◽  
Changjian Yuan ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Active Components

Abstract BackgroundCorydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used.Materials and MethodsThe active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform.Results49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsOverall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

scholarly journals Integrating Data Mining, Network Pharmacology, and Molecular Docking Verification to Investigate the Molecular Mechanism of Traditional Chinese Medicine Prescriptions for Treating Male Infertility

2021 ◽  
Author(s):  
Xue Bai ◽  
Yibo Tang ◽  
Qiang Li ◽  
Guimin Liu ◽  
Dan Liu ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Male Infertility ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Oxidant Stress ◽  
Estrogen Signaling ◽  
Network Pharmacology

Abstract Background: Male infertility (MI) affects almost 5% adult men worldwide, and 75% of these cases are unexplained idiopathic. There are limitations in the current treatment due to the unclear mechanism of MI, which highlight the urgent need for a more effective strategy or drug. Traditional Chinese Medicine (TCM) prescriptions have been used to treat MI for thousands of years, but their molecular mechanism is not well defined. Methods: Aiming at revealing the molecular mechanism of TCM prescriptions on MI, a comprehensive strategy integrating data mining, network pharmacology, and molecular docking verification was performed. Firstly, we collected 289 TCM prescriptions for treating MI from National Institute of TCM Constitution and Preventive Medicine for 6 years. Then, Core Chinese Materia Medica (CCMM), the crucial combination of TCM prescriptions, was obtained by the TCM Inheritance Support System from China Academy of Chinese Medical Sciences. Next, the components and targets of CCMM in TCM prescriptions and MI-related targets were collected and analyzed through network pharmacology approach.Results: The results showed that the molecular mechanism of TCM prescriptions for treating MI are regulating hormone, inhibiting apoptosis, oxidant stress and inflammatory. Estrogen signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway are the most important signaling pathways. Molecular docking experiments were used to further validate network pharmacology results. Conclusions: This study not only discovers CCMM and the molecular mechanism of TCM prescriptions for treating MI, but may be helpful for the popularization and application of TCM treatment.

scholarly journals Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Weilin Zheng ◽  
Jie Wang ◽  
Jiayi Wu ◽  
Tao Wang ◽  
Yangxue Huang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Active Role ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Mesenchymal Transition ◽  
Beneficial Effects ◽  
Function Modules

Endometriosis is a common gynecological disease and causes severe chronic pelvic pain and infertility. Growing evidence showed that traditional Chinese medicine (TCM) plays an active role in the treatment of endometriosis. ELeng Capsule (ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. However, the mechanisms of ELC have not been fully characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC. As a result, 40 compounds are identified, and 75 targets overlapped with endometriosis-related proteins. The mechanism of ELC for the treatment of endometriosis is based on the function modules of inducing apoptosis, inhibiting angiogenesis, and regulating immunity mainly through signaling molecules and interaction (neuroactive ligand–receptor interaction), immune system–associated pathways (toll-like receptor signaling pathway), vascular endothelial growth factor (VEGF) signaling, and MAPK signaling pathway based on network pharmacology. In addition, based on RNA-sequence analysis, we found that the mechanism of ELC was predominantly associated with the regulation of the function modules of actin and cytoskeleton, epithelial–mesenchymal transition (EMT), focal adhesion, and immunity-associated pathways. In conclusion, ELC exerted beneficial effects on endometriosis, and the potential mechanism could be realized through functional modules, such as inducing apoptosis and regulating angiogenesis, cytoskeleton, and EMT. This work not only provides insights into the therapeutic mechanism of TCM for treating endometriosis but also offers an efficient way for drug discovery and development from herbal medicine.

scholarly journals Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Tingting Fang ◽  
Lanqin Liu ◽  
wenjun liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Tripterygium Wilfordii ◽  
Active Ingredients ◽  
Acute Myeloid

Abstract Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore，this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology.Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database.Key findings. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway.Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.

scholarly journals A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qiaofeng Li ◽  
Taijin Lan ◽  
Songhua He ◽  
Weiwei Chen ◽  
Xiaolan Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Nicotinic Acid ◽  
Signaling Pathway ◽  
Antihypertensive Effect ◽  
Spontaneously Hypertensive Rat ◽  
Shikimic Acid ◽  
Network Pharmacology ◽  
Active Compounds

Abstract Background Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. Methods The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). Results LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. Conclusions LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.

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