Exploration of the pharmacological components and therapeutic mechanisms in treatment of Alzheimer's disease with Polygonati Rhizoma and its processed product using combined analysis of metabolomics, network pharmacology, and gut microbiota
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SUBMITTER: Xiaojuan L
PROVIDER: S-EPMC11336570 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8766719 | biostudies-literature
Project description:Alzheimer's disease (AD) has become a worldwide disease affecting human health and resulting in a heavy economic burden on the healthcare system. Polygonati rhizoma (PR), a kind of traditional Chinese medicine (TCM), is known to improve learning and memory abilities. However, its AD-treating material basis and therapeutic potential for the treatment of AD have remained unclear. Therefore, the present study aimed to uncover the key active ingredients of PR and its therapeutic potential for the treatment of AD. First, we used comparative metabolomics to identify the potential key active ingredients in the edible and medicinal PR. Second, network pharmacology was used to decipher the effects and potential targets of key active ingredients in the PR for the treatment of AD, and molecular docking was further used to identify the binding ability of those active ingredients with AD-related target of AChE. The rate of acetylcholinesterase (AChE) inhibition, oxidative stress, neuroprotective effects, and anti-inflammatory activity were assessed in vitro to screen the potential active ingredients in the PR with therapeutic potential against AD. Finally, APPswe/PS1dE9 AD mice were used to screen the therapeutic components in the PR. Seven overlapping upregulated differential metabolites were identified as the key active ingredients, among which cafestol, isorhamnetin, and rutin have AChE inhibitory activity, anti-inflammatory activity, and neuroprotective effects in vitro validation assays. Furthermore, in vivo results showed that cafestol, isorhamnetin, and rutin displayed several beneficial effects in AD transgenic mice by reducing the number of Aβ-positive spots and the levels of inflammatory cytokines, inhibiting the AChE activity, and increasing the antioxidant levels. Each compound is involved in a different function in the early stages of AD. In conclusion, our results corroborate the current understanding of the therapeutic effects of PR on AD. In addition, our work demonstrated that the proposed network pharmacology-integrated comparative metabolomics strategy is a powerful way of identifying key active ingredients and mechanisms contributing to the pharmacological effects of TCM.
| S-EPMC9385993 | biostudies-literature
Project description:A purified polysaccharide with a galactose backbone (SPR-1, Mw 3,622 Da) was isolated from processed Polygonati Rhizoma with black beans (PRWB) and characterized its chemical properties. The backbone of SPR-1 consisted of [(4)-β-D-Galp-(1]9 → 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp, with a branch chain of R1: β-D-Galp-(1 → 3)-β-D-Galp-(1→ connected to the →4,6)-β-D-Galp-(1→ via O-6, and a branch chain of R2: α-D-Glcp-(1 → 6)-α-D-Glcp-(1→ connected to the →4,6)-α-D-Glcp-(1→ via O-6. Immunomodulatory assays showed that the SPR-1 significantly activated macrophages, and increased secretion of NO and cytokines (i.e., IL-1β and TNF-α), as well as promoted the phagocytic activities of cells. Furthermore, isothermal titration calorimetry (ITC) analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant (K D) of 18.8 μM. It was suggested that SPR-1 activated the immune response through Toll-like receptor 4 (TLR4) signaling and downstream responses. Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response, and also provided an easily accessible way that can be used for PR deep processing.
| S-EPMC11342111 | biostudies-literature
Project description:Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.
| S-EPMC8526013 | biostudies-literature
Project description:BackgroundKeyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and underlying mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological mechanisms and components of KP-induced liver injury through animal experiments, UPLC-QTOF/MS combined with network pharmacology.MethodsFirstly, based on the immune stress mouse model, liver function parameters and hematoxylin-eosin (H&E) staining were detected to investigate KP-induced liver injury. The UPLC-QTOF/MS method was used to identify the components of KP. CTD database and literature mining were further applied to screen nonliver protective components. Subsequently, the nonliver protective components and their corresponding targets and targets of hepatotoxicity were analyzed by the method of network pharmacology. Finally, key targets from networked pharmacology were examined by the enzyme-linked immunosorbent assay (ELISA) and molecular docking.ResultsOur results indicated that KP had hepatotoxicity in male Kunming mice, which could favor hepatocyte necrosis and infiltration of inflammatory cells. A total of 70 nonliver protective compounds were identified and screened. The results of network pharmacology illustrated that methoxsalen, obacunone, limonin, and dictamnine might be the main compounds that caused liver damage. The potential hepatotoxicity mechanisms of KP might be through the IL17 and apoptosis pathways to regulate IL6, TNFα, CASP3, and CASP8 targets, thereby causing inflammation, excessive release of factors, and hepatocyte necrosis. The results of the ELISA experiments indicated that KP could increase the release of IL6 and TNFα inflammatory factors in liver tissues. Molecular docking suggested that methoxsalen, obacunone, limonin, and dictamnine had moderate binding ability with CASP3 and CASP8.ConclusionIn this study, the material basis and potential pharmacological mechanisms of KP-induced liver injury were preliminarily explored. Our research provides the initial theoretical basis for reducing the toxicity of KP.
| S-EPMC9744617 | biostudies-literature
Project description:Rhizoma Polygonati (huangjing in Chinese, ) is a medicine food homology herb used as a component of traditional Chinese medicine treating COVID-19 in the current pandemic emergency in China but the mechanisms remain elusive. Here using TCMSP and Swiss Target Prediction databases to sort out the potential targets of the main chemical components and GenCLiP3, NCBI, and GeneCard databases to search for COVID-19 related targets, the chemical compound-target-pathway network was analyzed. Each component was molecularly docked with host cell target angiotensin converting enzyme II, SARS-CoV-2 targets Spike protein, RNA-dependent RNA polymerase, or 3CL hydrolase. Our results showed a higher affinity of the compound diosgenin and (+)-Syringaresinol-O-beta-D-glucoside binding to the three SARS-CoV-2 proteins compared to the other compounds tested. Thus, our data suggest that potential compounds in Rhizoma Polygonati may act on different targets with viral and cancer related signaling and have a great potential in treatment of COVID-19.
| S-EPMC7427583 | biostudies-literature
Project description:The present study aimed to prepare polysaccharides from the pomace of Polygonatum rhizome and characterize their structural features and biological activities. After hot water extraction and DEAE-52 cellulose fractionation, a neutral polysaccharide (PKP) was obtained with 91.85% sugars and 0.45% proteins. Structural characterization indicated that PKP contained a main fraction with a molecular weight of 4.634 × 103 Da and was composed of →1)-β-D-Fruf-(2→ and →6)-β-D-Fruf-(2→ residues. PKP was a semi-crystalline polymer, and the Congo red assay suggested the presence of triple-helix structure in PKP. PKP exhibited moderate radical scavenging activity (including 15.55% inhibition of DPPH, 21.48% inhibition of ABTS, and 22.52% inhibition of ·OH) and could effectively protect MRC-5 cells from H2O2-induced oxidative damage at 0.01 mg/mL through inhibiting apoptosis, decreasing SA-β-galactosidase activity, and downregulating the expression levels of p16 and p53. Therefore, PKP could be used in functional foods and pharmaceuticals as an antioxidant. This study provides an attractive method for utilizing polysaccharides from waste materials.
| S-EPMC11402156 | biostudies-literature
Project description:Migraine is a common neurological disorder that manifests as recurrent attacks of unilateral and throbbing headache. Conioselinum anthriscoides "Chuanxiong" (Apiaceae; Chuanxiong rhizoma) and Cyperus rotundus L. (Cyperaceae; Cyperi rhizoma) (CRCR), is a classic prescription for treating migraine. This study aimed to reveal the potential mechanisms of CRCR extract against migraine using integrated analysis of metabolomics and network pharmacology. Behavioral changes in the nitroglycerin rat migraine model were determined from von Frey withdrawal response. Untargeted serum metabolomics was used to identify the differentially expressed metabolites and metabolic pathways. The differentially expressed metabolites were analyzed to obtain the corresponding targets by a compound-reaction-enzyme-gene network. Network pharmacology was used to construct a compound-target-pathway network. The common targets of metabolomics and network pharmacology were further analyzed. Metabolomics analysis identified 96 differentially expressed metabolites and 77 corresponding targets. Network pharmacology analysis identified 201 potential targets for CRCR against migraine. By intersecting 77 targets with 201 targets, monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), and catechol-O-methyltransferase (COMT) were identified as the common targets, and MAO-A, MAO-B, and COMT were involved in the tyrosine metabolism pathway. Further experiments demonstrated that the contents of MAO-A and COMT were significantly increased in serum and brainstem tissue of the migraine rats. CRCR extract significantly decreased the contents of MAO-A and COMT, while no significant difference was found in MAO-B. Metabolomics analysis indicated that the contents of 3,4-dihydroxyphenylacetate (DOPAC) and 3-(4-hydroxyphenyl)pyruvate (HPP) were significantly increased in the migraine rats, and CRCR extract caused significant decreases in DOPAC and HPP. Interestingly, DOPAC and HPP were two differentially expressed metabolites involved in the tyrosine metabolism pathway. Correlation analysis showed that DOPAC and HPP were highly positively correlated with MAO-A and COMT. Taken together, two key differentially expressed metabolites (DOPAC and HPP), two key targets (MAO-A and COMT), and one relevant metabolic pathway (tyrosine metabolism) showed great importance in the treatment of migraine. This research could provide a new understanding of the potential mechanism of CRCR against migraine. More attentions should be paid into the tyrosine metabolism pathway in future studies.
| S-EPMC8987590 | biostudies-literature
Project description:BACKGROUND Acori Tatarinowii Rhizoma (ATR), a traditional Chinese herbal medicine, is used to treat Alzheimer's disease (AD), which is a worldwide degenerative brain disease. The aim of this study was to identify the potential mechanism and molecular targets of ATR in AD by using network pharmacology. MATERIAL AND METHODS The potential targets of the active ingredients of ATR were predicted by PharmMapper, and the targets of Alzheimer's disease were searched by DisGeNET. All screened genes were intersected to obtain potential targets for the active ingredients of ATR. The protein-protein interaction network of possible targets was established by STRING, GO Enrichment, and KEGG pathway enrichment analyses using the Annotation of DAVID database. Next, Cytoscape was used to build the "components-targets-pathways" networks. Additionally, a "disease-component-gene-pathways" network was constructed and verified by molecular docking methods. In addition, the active constituents ß-asarone and ß-caryophyllene were used to detect Aß₁₋₄₂-mediated SH-SY5Y cells, and mRNA expression levels of APP, Tau, and core target genes were estimated by qRT-PCR. RESULTS The results showed that the active components of ATR participate in related biological processes such as cancer, inflammation, cellular metabolism, and metabolic pathways and are closely related to the 13 predictive targets: ESR1, PPARG, AR, CASP3, JAK2, MAPK14, MAP2K1, ABL1, PTPN1, NR3C1, MET, INSR, and PRKACA. The ATR active components of ß-caryophyllene significantly reduced the mRNA expression levels of APP, TAU, ESR1, PTPN1, and JAK2. CONCLUSIONS The targets and mechanism corresponding to the active ingredients of ATR were investigated systematically, and novel ideas and directions were provided to further study the mechanism of ATR in AD.
| S-EPMC7304315 | biostudies-literature
Project description:Natural products from culture collections have enormous impact in advancing discovery programs for metabolites of biotechnological importance. These discovery efforts rely on the metabolomic characterization of strain collections. Many emerging approaches compare metabolomic profiles of such collections, but few enable the analysis and prioritization of thousands of samples from diverse organisms while delivering chemistry specific read outs. In this work we utilize untargeted LC-MS/MS based metabolomics together with molecular networking to. This approach annotated 76 molecular families (a spectral match rate of 28 %), including clinically and biotechnologically important molecules such as valinomycin, actinomycin D, and desferrioxamine E. Targeting a molecular family produced primarily by one microorganism led to the isolation and structure elucidation of two new molecules designated maridric acids A and B. Molecular networking guided exploration of large culture collections allows for rapid dereplication of know molecules and can highlight producers of uniques metabolites. These methods, together with large culture collections and growing databases, allow for data driven strain prioritization with a focus on novel chemistries.
| S-EPMC5556696 | biostudies-literature