Network Pharmacology-Based Approach Uncovers the Mechanism of GuanXinNing Tablet for Treating Thrombus by MAPKs Signal Pathway

Wang, Mulan; Yang, Qian; Ying, Xuhui; Li, Yuanyuan; Wu, Yang; Shou, Qiyang; Ma, Quan-Xin; Zhu, Zi-Wei; Chen, Minli

doi:10.3389/fphar.2020.00652

Cited by 17 publications

(16 citation statements)

References 46 publications

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“…Z20150028). We identified the main constituents of GXN using LC–MS analysis by referring to previous methods [ 13 ]. As shown in Figure 1 , the most abundant constituents in GXN are salvianolic acid B (peak 9), rosmarinic acid (peak 7), ferulic acid (peak 5), tanshinol (peak 1), chlorogenic acid (peak 3), caffeic acid (peak 4), and salvianolic acid A (peak 10), which are generally consistent with the results reported by Wang et al [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…and Ligusticum chuanxiong Hort. [ 13 ]. According to our previous liquid chromatography-mass spectrometry (LC–MS) analysis, the main constituents of GXN include salvianolic acid B, ferulic acid, and salvianolic acid A [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although GXN exerts multiple pharmacological effects, such as inhibiting platelet aggregation and antioxidant, anti-inflammatory, and vascular endothelium protection activities [ 13 ], the effects of GXN on AD remain unclear. In addition, studies have found that S. miltiorrhiza Bge., L. chuanxiong Hort., and their active ingredients exert neuroprotective effects [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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GuanXinNing Tablet Attenuates Alzheimer’s Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits

Zhang

Shen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Based on accumulating evidence, Alzheimer’s disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aβ), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aβ deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GuanXinNing Tablet Attenuates Alzheimer’s Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits

Zhang

Shen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Extraction of GXN powder was conducted as previously described ( Wang et al, 2020 ). In brief, Salvia miltiorrhiza and Ligusticum chuanxiong (10 kg each) were added to 160 L of water, which was heated and kept at a low boil for 2 h. After pouring out the supernatant, the remaining residue was extracted twice again with 120 L of water and boiled for 1.5 h. All the supernatants were combined and concentrated to approximately 9 L at 60°C in a rotary evaporator, followed by the addition of 35 L of a 95% ethanol solution and overnight incubation.…”

Section: Methodsmentioning

confidence: 99%

Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism

Ling

Shi²,

et al. 2021

Front. Pharmacol.

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Vasodilatory therapy plays an important role in the treatment of cardiovascular diseases, especially hypertension and coronary heart disease. Previous research found that Guanxinning tablet (GXNT), a traditional Chinese compound preparation composed of Salvia miltiorrhiza (Danshen) and Ligusticum chuanxiong (Chuanxiong), increase blood flow in the arteries, but whether vasodilation plays a role in this effect remains unclear. Here, we found that GXNT significantly alleviated the vasoconstriction of isolated rabbit thoracic aorta induced by phenylephrine (PE), norepinephrine (NE), and KCl in a dose-dependent manner with or without endothelial cells (ECs). Changes in calcium ion levels in vascular smooth muscle cells (VSMCs) showed that both intracellular calcium release and extracellular calcium influx through receptor-dependent calcium channel (ROC) declined with GXNT treatment. Experiments to examine potassium channels suggested that endothelium-denuded vessels were also regulated by calcium-activated potassium channels (Kca) and ATP-related potassium channels (KATP) but not voltage-gated potassium channels (kv) and inward rectifying potassium channels (KIR). For endothelium-intact vessels, the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contents in vascular tissue obviously increased after GXNT treatment, and pretreatment with the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) or guanylyl cyclase inhibitor methylthionine chloride (MB) significantly inhibited vasodilation. An assessment of NO-related pathway protein expression revealed that GXNT enhanced the expression of phosphorylated endothelial NO synthase (eNOS) in a dose-dependent manner but had no effect on total eNOS, p-Akt, Akt, or PI3K levels in human umbilical vein ECs (HUVECs). In addition to PI3K/AKT signaling, Ca2+/calmodulin (CaM)-Ca2+/CaM-dependent protein kinase II (CaMKII) signaling is a major signal transduction pathway involved in eNOS activation in ECs. Further results showed that free calcium ion levels were decreased in HUVECs with GXNT treatment, accompanied by an increase in p-CaMKII expression, implying an increase in the Ca2+/CaM-Ca2+/CaMKII cascade. Taken together, these findings suggest that the GXNT may have exerted their vasodilative effect by activating the endothelial CaMKII/eNOS signaling pathway in endothelium-intact rings and calcium-related ion channels in endothelium-denuded vessels.

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“…Network pharmacology combines systems biology with biological network construction and analysis to assess the effectiveness and metabolic characteristics of drugs ( Huang et al, 2014 ). It takes advantage of information networks based on high-throughput omics data analysis, virtual computing, and database retrieval ( Wang et al, 2020 ). In particular, it has been applied in elucidating the synergistic multi-component, multi-target, and multi-pathway effect of TCM prescriptions and in clarifying drug action mechanism.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Cornus Officinalis and Paeonia Lactiflora in Rheumatoid Arthritis via Network Pharmacology Analysis

Huang

et al. 2021

Front. Pharmacol.

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Cornus officinalis Sieb et. Zucc and Paeonia lactiflora Pall. have exhibited favorable therapeutic effects against rheumatoid arthritis (RA), but the specific mechanisms of their active compounds remain unclear. The aim of this study was to comprehensively analyze the therapeutic mechanisms of selected active compounds in Cornus officinalis (loganin, ursolic acid, and morroniside) and Paeonia lactiflora (paeoniflorin and albiflorin) via network pharmacology. The pharmacological properties of the five active compounds were evaluated and their potential target genes were identified by database screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analysis were performed to determine the enriched molecular pathways associated with the active compounds. Using network pharmacology tools, eight genes (IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3) were identified as common targets between RA and the five active compounds. Molecular docking simulation revealed the compound-target relationship between the five active compounds and three selected targets from the eight common ones (LGALS3, STAT3, and VEGFA). The compound-target relationships were subsequently validated via preliminary in vivo experiments in a rat model of collagen-induced arthritis. Rats subjected to collagen-induced arthritis showed increased protein expression of LGALS3, STAT3, and VEGFA in synovial tissues. However, treatment using Cornus officinalis or/and Paeonia lactiflora, as well as their most drug-like active compounds (ursolic acid or/and paeoniflorin, respectively, identified based on pharmacological properties), attenuated the expression of these three targets, as previously predicted. Collectively, network pharmacology allowed the pharmacological and molecular roles of Cornus officinalis and Paeonia lactiflora to be systematically revealed, further establishing them as important candidate drugs in the treatment and management of RA.

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Network Pharmacology-Based Approach Uncovers the Mechanism of GuanXinNing Tablet for Treating Thrombus by MAPKs Signal Pathway

Cited by 17 publications

References 46 publications

GuanXinNing Tablet Attenuates Alzheimer’s Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits

GuanXinNing Tablet Attenuates Alzheimer’s Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits

Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Cornus Officinalis and Paeonia Lactiflora in Rheumatoid Arthritis via Network Pharmacology Analysis

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