Homotherapy for heteropathy of Alzheimer's disease and anemia through reducing the expression of toll-like receptor and TNF by steamed Panax notoginseng.

One of the effects of Steamed Panax notoginsen (SPN) is to replenish blood, which is mostly used to treat anemia in clinic. SPN has the effect of treating anemia and Alzheimer's disease (AD) in clinical and basic research. In traditional Chinese medicine, anemia and AD have the same characteristics, and their symptoms are qi and blood deficiency. First, data analysis was carried out through network pharmacology to predict the action targets of SPN homotherapy in the treatment of AD and anemia. Specifically, TCMSP and relevant literature were used to screen the main active ingredients of Panax notoginseng, and SuperPred was used to predict the action targets of the active ingredients. Disease targets related to AD and anemia were collected through Genecards database, and STRING and protein interaction (PPI) was used for enrichment analysis, Analyze the characteristics of the active ingredient target network on the Cytascape 3.9.0 platform, and use Metascape to enrich the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment (KEGG pathway). Then Drosophila was used as the AD animal model, and the effects of SPN on the climbing ability, olfactory memory and brain Aβ, with rats as anemia animal models, the improvement effect of SPN on blood routine and organ index of rats with blood deficiency induced by CTX and APH was analyzed to further explain the therapeutic effect of SPN on these two diseases. Finally, the regulatory effect of SPN on the key active target of allotherapy for AD and anemia was verified by PCR. After the screening, 17 active components and 92 action targets of SPN were obtained. The degree values of components and the first 15 targets are NFKB1, IL10, PIK3CA, PTGS2, SRC, ECFR, CASP3, MTOR, IL1B, ESR1, AKT1, HSP90AA1, IL6, TNF, and Toll-like receptor, it is mainly related to inflammatory response, immune regulation and antioxidation. SPN improved the climbing ability, olfactory memory ability, and Aβ42 content in the brain of Aβ flies, and significantly reduced the expression of TNF and Toll-like receptor in the brain after treatment. SPN can significantly improve the blood routine index and organ index of anemia rats, and also significantly reduce the expression of TNF and Toll-like receptor in the brain after treatment. SPN can regulate the expression of TNF and Toll-like receptor to achieve the same treatment of AD and anemia.

Mengnan L ，Xianwen Y ，Shuyan Z ，Shuiqing C ，Wenjuan X ，Xuan W ，Jia W ，Chunshuai L ，Linlin Y ，Xinfang X ，Xiangri L ... -  《-》

Steamed Panax notoginseng attenuates renal anemia in an adenine-induced mouse model of chronic kidney disease.

Panax notoginseng (PN) (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a "blood-tonifying" function according to the traditional use. However, its pharmacological effect and mechanism on alleviating renal anemia (RA) are still unclear. The study aims to investigate the effect of steamed Panax notoginseng (SPN) to attenuate RA and its underlying mechanism based on the model of adenine-induced RA mice. Seventy mice were randomly divided into seven groups of ten: the control group, model group, the erythropoietin (EPO) group, the Fufang E'jiao Jiang (FEJ) group, the high-dose steamed PN (H-SPN) group, the middle-dose steamed PN (M-SPN) group, and the low-dose steamed PN (L-SPN) group. The adenine induction RA model was applied to assess the "blood enriching" function of SPN. The blood routine indexes, erythrocyte fragility, pathologic morphology of kidney tissue and the expression levels of related cytokines and proteins in the mice were detected after 3-week administration with SPN and positive drugs. Our study provided evidences that SPN could ameliorate RA. Compared with the control group, SPN could attenuate RA by significantly increasing the numbers of peripheral blood cells (p < 0.01), improving the erythrocyte fragility (p < 0.01), and restoring the expression of EPO mRNA in the kidneys and EPO receptor mRNA in bone marrow nucleated cells. The expression of TGF-β1 mRNA was declined and the expression of HGF mRNA was significantly increased in a dose-dependent way after the treatment of SPN. Additionally, the expression of Bcl-2 and Bcl-2/Bax ratio in the kidneys were significantly increased. In contrast, there was a highly significant decrease in the expression of Bax (p < 0.01), following SPN treatment. SPN could alleviate RA by promoting the overall hematopoiesis and inhibiting the progress of renal injury in mice.

Gao M ，Zhang Z ，Zhang Y ，Li M ，Che X ，Cui X ，Wang M ，Xiong Y ... -  《-》

[Mechanism of Panax notoginseng saponins in treating diabetic kidney disease based on network pharmacology and experimental verification].

Wang YC ，Geng RY ，Yang JH ，Ma C ，Dai W ，Guo YL ，Zhang HT ，Xu ZX ，Li XY ，Ma XX ，Hu JP ，Wen LM ... -  《-》

Integration of Network Pharmacology and Molecular Docking Technology Reveals the Mechanism of the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease.

So far, only a few researchers have systematically analyzed the constituents of the traditional Chinese medicine prescription Xixin Decoction (XXD) and its potential mechanism of action in treating Alzheimer's disease (AD). This study aimed to explore the potential mechanism of XXD in the treatment of AD using network pharmacology and molecular docking. The compounds of XXD were searched within the Traditional Chinese Medicine System Pharmacology Database (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) databases. Overlapping AD-related targets obtained from the two databases and the predicted targets of XXD obtained from SwissTargetPrediction platform were imported into the STRING database to build PPI networks including hub targets; Cytoscape software was used to construct the herb-compound-target network while its plug-in CytoNCA was used to screen the main active compounds of XXD. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses explored the core biological mechanism and pathways via the Metascape platform. In addition, we used AutoDock Vina and PyMOL software to investigate the molecular docking of main compounds to hub targets. We determined 114 active compounds, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets.Protein-protein interaction (PPI) network identified 9 hub targets. The hub targets were found to be majorly enriched in several biological processes (positive regulation of kinase activity, positive regulation of cell death, regulation of MAPK cascade, trans-synaptic signaling, synaptic signaling, etc.) and the relevant pathways of Alzheimer's disease, including neuroactive ligand-receptor interaction, dopaminergic synapse, serotonergic synapse, and the MAPK signaling pathway, etc. The pathway-target-compound network of XXD for treating AD was then constructed. 8 hub targets exhibited good binding activity with 9 main active compounds of XXD in molecular docking. In this study, we found multi-compound-multi-target-multi-pathway regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. XXD may play a therapeutic role through regulating the Alzheimer's disease pathway, its downstream PI3K/Akt signaling pathway or the MAPK signaling pathway, thereby treating AD. This provides new insights for further experiments on the pharmacological effects of XXD.

Zhang Z ，Xu J ，Ma S ，Lin N ，Hou M ，Wei M ，Li T ，Shi J ... -  《-》

Molecular mechanisms of Huanglian Jiedu decoction in treating Alzheimer's disease by regulating microbiome via network pharmacology and molecular docking analysis.

Huanglian Jiedu decoction (HLJDD) is a famous traditional Chinese medicine prescription, which is widely used in the treatment of Alzheimer's disease (AD). However, the interaction between bioactive substances in HLJDD and AD-related targets has not been well elucidated. A network pharmacology-based approach combined with molecular docking was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HLJDD against AD, through the regulation of microbial flora. Bioactives and potential targets of HLJDD, as well as AD-related targets, were retrieved from Traditional Chinese Medicine Systems Pharmacology Analysis Database (TCMSP). Key bioactive components, potential targets, and signaling pathways were obtained through bioinformatics analysis, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was performed to predict the binding of active compounds with core targets. 102 bioactive ingredients of HLJDD and 76 HLJDD-AD-related targets were screened. Bioinformatics analysis revealed that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, (R)-canadine may be potential candidate agents. AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9 and CASP3 could become potential therapeutic targets. 15 important signaling pathways including the cancer pathway, VEGF signaling pathway, and NF-κB signaling pathway might play an important role in HLJDD against AD. Moreover, molecular docking analysis suggested that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, and (R)-canadine combined well with AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9, CASP3, respectively. Our results comprehensively illustrated the bioactives, potential targets, and possible molecular mechanisms of HLJDD against AD. HLJDD may regulate the microbiota flora homeostasis to treat AD through multiple targets and multiple pathways. It also provided a promising strategy for the use of traditional Chinese medicine in treating human diseases.

Zheng R ，Shi S ，Zhang Q ，Yuan S ，Guo T ，Guo J ，Jiang P ... -  《Frontiers in Cellular and Infection Microbiology》