Saponins of ginseng products: a review of their transformation in processing.

The primary processed product of Panax ginseng C.A. Meyer (P. ginseng) is red ginseng. As technology advances, new products of red ginseng have arisen. Red ginseng products, e.g., traditional red ginseng, sun ginseng, black ginseng, fermented red ginseng, and puffed red ginseng, are commonly used in herbal medicine. Ginsenosides are the major secondary metabolites of P. ginseng. The constituents of P. ginseng are significantly changed during processing, and several pharmacological activities of red ginseng products are dramatically increased compared to white ginseng. In this paper, we aimed to review the ginsenosides and pharmacological activities of various red ginseng products, the transformation law of ginsenosides in processing, and some clinical trials of red ginseng products. This article will help to highlight the diverse pharmacological properties of red ginseng products and aid in the future development of red ginseng industrialization.

Exploring the common pathogenesis of Alzheimer's disease and type 2 diabetes mellitus via microarray data analysis.

Background: Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated. Purpose: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM. Methods: Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs). Results: The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aß and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases. Conclusion: The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.

Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Coptidis Rhizoma for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is becoming a more prevalent public health issue in today's culture. The experimental study of Coptidis Rhizoma (CR) and its chemical components in AD treatment has been widely reported, but the principle of multi-level and multi-mechanism treatment of AD urgently needs to be clarified. Objective: This study focuses on network pharmacology to clarify the mechanism of CR's multi-target impact on Alzheimer's disease. Methods: The Phytochemical-compounds of CR have been accessed from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Symmap database or HPLC determination. The values of Oral Bioavailability (OB) ≥ 30% and Drug Like (DL) ≥ 0.18 or blood ingredient were used to screen the active components of CR; the interactive network of targets and compounds were constructed by STRING and Cytoscape platform, and the network was analyzed by Molecular Complex Detection (MCODE); Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) and metabolic pathway enrichment of targets were carried out with Metascape, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and MetaboAnalyst platform; Based on CytoHubba, the potential efficient targets were screened by Maximal Clique Centrality (MCC) and Degree, the correlation between potential efficient targets and amyloid ß-protein (Aß), Tau pathology was analyzed by Alzdata database, and the genes related to aging were analyzed by Aging Altas database, and finally, the core targets were obtained; the binding ability between ingredients and core targets evaluated by molecular docking, and the clinical significance of core targets was assessed with Gene Expression Omnibus (GEO) database. Results: 19 active components correspond to 267 therapeutic targets for AD, of which 69 is potentially effective; in module analysis, RELA, TRAF2, STAT3, and so on are the critical targets of each module; among the six core targets, RELA, MAPK8, STAT3, and TGFB1 have clinical therapeutic significance; GO function, including 3050 biological processes (BP), 257 molecular functions (MF), 184 cellular components (CC), whose functions are mainly related to antioxidation, regulation of apoptosis and cell composition; the HIF-1 signaling pathway, glutathione metabolism is the most significant result of 134 KEGG signal pathways and four metabolic pathways, respectively; most of the active components have an excellent affinity in docking with critical targets. Conclusion: The pharmacological target prediction of CR based on molecular network pharmacology paves the way for a multi-level networking strategy. The study of CR in AD treatment shows a bright prospect for curing neurodegenerative diseases.

The Pharmacological Mechanism of Xiyanping Injection for the Treatment of Novel Coronavirus Pneumonia (COVID-19): Based on Network Pharmacology Strategy.

Purpose: The possible mechanism of Xiyanping injection treatment COVID-19 is discussed through the network pharmacology. Methods: Obtaining the chemical structure of Xiyanping injection through the patent application and obtaining control compounds I, II, III, IV, V, Yanhuning injection (VI, VII), Chuanhuning injection (VIII, IX), 10 compounds were analyzed by D3Targets-2019-nCoV. The human anti-COVID-19 gene in COVID-19 DisGeNET was intersected with the CTD Andrographolide target gene and then combined with D3Targets-2019-nCoV, resulting in 93 genes, using the Venny 2.1 platform. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. The GO, KEGG, and tissue of the target were analyzed using the Metascape platform and DAVID platform. The gene expression in the respiratory system was analyzed using the ePlant platform. The CB-Dock is used for the docking verification and degree values of the first 20 genes. Results: Finally, 1599 GO and 291 KEGG results were obtained. GO is mostly associated with the cell stress response to chemicals, the cell response to oxidative stress, and the cell response to reactive oxygen species. In total, 218 KEGG pathway concentrations were related to infection and other diseases and 73 signaling pathways mostly related to inflammation and immune pathways, such as TNF signaling pathway and MAPK signaling pathway. The molecular docking results show that Xiyanping injection, compound III, has a good docking relationship with 20 target proteins such as HSP90AA1. Tissue has 22 genes that are pooled in the lungs. Conclusion: Xiyanping injection may inhibit the release of various inflammatory factors by inhibiting intracellular pathways such as MAPK and TNF. It acts on protein targets such as HSP90AA1 and plays a potential therapeutic role in COVID-19. Thus, compound III may be treated as a potential new drug for the treatment of COVID-19 and the Xiyanping injection may treat patients with COVID-19 infection.

Study on the mechanism of treating COVID-19 with Shenqi Wan based on network pharmacology.

PURPOSE: Through the method of network pharmacology, the active components and targets of Shenqi Wan (SQW) were excavated, the relationship with novel Coronavirus pneumonia (COVID-19) was discussed, and the possible mechanism of SQW in the treatment of COVID-19 was revealed from the aspects of multicomponents, multitargets, and multipathways. METHODS: Firstly, the active components of SQW were screened from traditional Chinese medicine systems pharmacology database and analysis platform and the 2020 edition of Chinese Pharmacopeia, and the related targets of the components were obtained. Then the disease targets related to COVID-19 were screened from GeneCards and Online Mendelian Inheritance in Man. Venny was used to map the relationship between component-target and disease-target, and String was used to analyze the interaction of common targets. The network was constructed and analyzed by Cytoscape, the function of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) genes was enriched by Metascape, and the molecular docking was verified by CB-Dock. RESULTS: Finally, 45 active components of SQW were obtained, and 72 potential targets were related to COVID-19, angiotensin-converting enzyme 2 (ACE2), interleukin (IL)-6, nitric oxide synthase (NOS3) and, C-reactive protein (CRP),may be the key targets. GO enrichment of 1715 projects, such as lipopolysaccharide stress response, active oxygen metabolism, positive regulation of cell migration, and other GO enrichment. About 136 KEGG pathways, tumor necrosis factor signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor 1-α signaling pathway were obtained. Molecular docking showed that kaempferol, quercetin, luteolin, astragaloside, calyx isoflavone glucoside, matrine, and other COVID-19-related targets such as ACE2, chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), prostaglandin-endoperoxide synthase 2 (PTGS2) have good binding ability. CONCLUSION: According to the above results, it is suggested that SQW may play a role in the treatment of COVID-19 by directly or indirectly combining kaempferol, quercetin, and luteolin with ACE2, 3CLpro, PLpro, and PTGS2 to regulate multiple biological functions and signaling pathways.

[Study on mechanism of combination of Platycodonis Radix and Lilii Bulbus with homology of medicine and food in treating pneumonia].

To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.

Uncovering the mechanism of the effects of Paeoniae Radix Alba on iron-deficiency anaemia through a network pharmacology-based strategy.

BACKGROUND: Paeoniae Radix Alba, the root of the plant Paeonia lactiflora Pall, is a common blood-enriching drug in traditional Chinese medicine. Its effectiveness in the clinical treatment of anaemia is remarkable, but its potential pharmacologic mechanism has not been clarified. METHODS: In this study, the potential pharmacologic mechanism of Paeoniae Radix Alba in the treatment of iron-deficiency anaemia was preliminarily elucidated through systematic and comprehensive network pharmacology. RESULTS: Specifically, we obtained 15 candidate active ingredients from among 146 chemical components in Paeoniae Radix Alba. The ingredients were predicted to target 77 genes associated with iron-deficiency anaemia. In-depth analyses of these targets revealed that they were mostly associated with energy metabolism, cell proliferation, and stress responses, suggesting that Paeoniae Radix Alba helps alleviate iron-deficiency anaemia by affecting these processes. In addition, we conducted a core target analysis and a cluster analysis of protein-protein interaction (PPI) networks. The results showed that four pathways, the p53 signalling pathway, the IL-17 signalling pathway, the TNF signalling pathway and the AGE-RAGE signalling pathway in diabetic complications, may be major pathways associated with the ameliorative effects of Paeoniae Radix Alba on iron-deficiency anaemia. Moreover, molecular docking verified the credibility of the network for molecular target prediction. CONCLUSIONS: Overall, this study predicted the functional ingredients in Paeoniae Radix Alba and their targets and uncovered the mechanism of action of this drug, providing new insights for advanced research on Paeoniae Radix Alba and other traditional Chinese medicines.