Anti-Oxidant and Anti-Inflammatory Substance Generated Newly in Paeoniae Radix Alba Extract Fermented with Plant-Derived Lactobacillus brevis 174A.
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ABSTRACT:
SUBMITTER: Shakya S
PROVIDER: S-EPMC8300999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota.
| S-EPMC9878331 | biostudies-literature
Project description:The Radix Bupleuri and Radix Paeoniae Alba herb-pair (RRH) are the most classic compatible drug pair for the treatment of hepatitis. However, the underlying mechanism remains unclear. Therefore, network pharmacology and molecular docking were conducted to investigate the prospective therapeutic constituents, targets, and pharmacological mechanisms of RRH in the treatment of hepatitis. The active components of RRH from the TCMSP database and disease-related targets from the OMIM, PharmGkb, GeneCards, TTD, and DrugBank databases were identified. The "drug-target-disease" network diagram and protein-protein interaction (PPI) network were constructed using Cytoscape (v3.8.0) and Online STRING 11.0. GO and KEGG pathway enrichment analyses were performed using R version 4.1.2, and molecular docking was performed to verify the results. We placed 176 overlapping cross genes into Online STRING 11.0 and obtained 14 core targets. A "Component-Target-GO-KEGG" network diagram was constructed, which was composed of 7 components, 14 targets, 10 biological processes, and 10 signal pathways. A total of 2413 GO biological processes and 174 KEGG pathways were explored for hepatitis treatment. Quercetin, kaempferol, isorhamnetin, and beta-sitosterol, which are the main bioactive components, were employed to bind the disease's hub targets, ensuring fulfillment of spatial and energy matching. The anti-hepatitis mechanism of RRH may be associated with several targets including RELA, AKT1, JUN, MAPK1, TP53, CCND1, MYC, NFKBIA, CDKN1A, and their respective signaling pathways. The main bioactive components in RRH, including quercetin, kaempferol, isorhamnetin, and beta-sitosterol, were used to bind the hub targets of the disease, which may provide insights into drug development for hepatitis.
| S-EPMC10695497 | biostudies-literature
Project description:Objective: We aimed to explore and verify the mechanism underlying the action of the active ingredients of Paeoniae Radix Alba (PRA) in the treatment of rheumatoid arthritis (RA). Methods: The protein targets of PRA’s six active ingredients and RA were identified. Then, the intersection of the two groups was studied. The drug–target network was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to analyze these genes. Furthermore, we validated our predictions of the potential targets through a docking study. Finally, the anti-inflammatory effect of Palbinone (PB), one of the active ingredients of PRA, was tested by conducting in vitro and in vivo studies. Results: Six active ingredients of PRA were identified, and 103 overlapping genes were discovered. Functional enrichment analysis indicated that the genes are mostly enriched in IL-17 signaling pathway, Th17 cell differentiation, and the FoxO, ErbB, and TNF signaling pathways. 10 hub genes and two gene cluster modules were identified by Cytoscape. Molecular docking analysis proved that PB was able to bind to the ATP binding site of Janus kinase (JAK)1, thereby acting as a potential inhibitor of JAK1. In vitro and in vivo studies demonstrated that PB exerts its anti-inflammatory role via the inhibition of JAK1. Conclusion: We constructed a multitarget pharmacological network of PRA in RA treatment. PB, one of the active compounds of PRA, was demonstrated to be a promising inhibitor of JAK1.
| S-EPMC9527307 | biostudies-literature
Project description:ObjectiveThe mechanism of action and potential targets of Paeoniae RadixAlba (Baishao, B) in the treatment of adjuvant-induced arthritis (AIA) rats are explained using metabolomics and network pharmacology techniques, and the research evidence for the development of anti-rheumatoid arthritis (RA) drugs is enriched.MethodsThe rats were injected with Freund's complete adjuvant (CFA) to induce arthritis. We then measured the general physical characteristics, examined their X-rays and histopathology to evaluate the pathological condition of the inflammation models, and conducted metabolomics studies on the change in urine metabolism caused by CFA. The lyophilized powder of B at a dose of 2.16 g/kg was orally administered to the rats continuously for 28 days, and the therapeutic effect was evaluated. Network pharmacology prediction shows that B contains the target action of the ingredient, and the simulation of the target molecular docking, in combination with the metabolomics analysis results, shows that B has a potential role in the treatment of AIA rats.ResultsB can reduce the paw swelling and pathological changes in rats caused by CFA, reverse the levels of 12 urine biomarkers, and regulate histidine metabolism, phenylalanine metabolism, arginine, proline metabolism, pyrimidine metabolism, etc. The prediction of the active ingredient target in B indicates that it may act as an inflammatory signaling pathway in anti-RA, among them being paeoniflorin, palbinone, beta-sitosterol, kaempferol, and catechin, which are the significant active ingredients.ConclusionThe metabolomics results revealed the markers and metabolic mechanisms of urinary metabolic disorders in rats with AIA, demonstrated the efficacy of the therapeutic effect of B, and identified the key ingredients in B, providing theoretical support for the subsequent development and utilization of B.
| S-EPMC9609690 | biostudies-literature
Project description:The use of yeast assist kefir fermentation, but also can cause food spoilage if uncontrolled. Hence, in this study, the microbial composition of an existing commercial kefir starter was modified to produce a functional starter, where Lactobacillus acidophilus KCNU and Lactobacillus brevis Bmb6 were used to replace yeast in the original starter to produce non-yeast kefir-like fermented milk. The functional starter containing L. acidophilus KCNU and L. brevis Bmb6 demonstrated excellent stability with 1010 CFU/g of total viable cells throughout the 12 weeks low-temperature storage. The newly developed functional starter also displayed a similar fermentation efficacy as the yeast-containing control starter, by completing the milk fermentation within 12 h, with a comparable total number of viable cells (108 CFU/mL) in the final products, as in control. Sensory evaluation revealed that the functional starter-fermented milk highly resembled the flavor of the control kefir, with enhanced sourness. Furthermore, oral administration of functional starter-fermented milk significantly improved the disease activity index score by preventing drastic weight-loss and further deterioration of disease symptoms in DSS-induced mice. Altogether, L. acidophilus KCNU and L. brevis Bmb6 have successfully replaced yeast in a commercial starter pack to produce a kefir-like fermented milk beverage with additional health benefits. The outcome of this study provides an insight that the specific role of yeast in the fermentation process could be replaced with suitable probiotic candidates.
| S-EPMC7372993 | biostudies-literature
Project description:Combination of Aconiti Lateralis Radix Praeparata (FZ) and Paeoniae Radix Alba (BS) shows a significant effect in rheumatoid arthritis (RA). This study aimed to investigate the efficacy enhancing and toxicity reducing mechanism of combination of them in adjuvant-induced arthritis (AIA) rats by metabolomics. Rats were randomly divided into seven groups, including A (healthy control), B (model control), C1 (therapy group), C2 (efficacy enhancing group), D1 (toxicity group), and D2 (toxicity reducing group), and dexamethasone group was used as positive control. The plasma biochemical indexes showed that therapeutic dose of lipid-soluble alkaloids of FZ could significantly inhibit the concentrations of IL-1β, TNF-α, and IFN-γ in AIA rats, and combination with total glucosides of peony could further reduce the concentration of IL-1β. Then, UPLC-LTQ/Orbitrap MS with untargeted metabolomics was performed to identify the possible metabolites and pathways. Through multivariate data analysis of therapeutic dose groups (A vs. B vs. C1 vs. C2) and multivariate data analysis of toxic dose groups (A vs. B vs. D1 vs. D2), 10 and 7 biomarkers were identified based on biomarker analysis, respectively. After inducing AIA model, the plasma contents of spermidine, vanillylmandelic acid, catechol, and linoleate were increased significantly, and the contents of citric acid, L-tyrosine, L-phenylalanine, leucine, L-tryptophan, and uridine 5'-monophosphate (UMP) were decreased significantly. High dose of lipid-soluble alkaloids of FZ could increase the plasma contents of L-lysine, L-arginine, and deoxycholic acid, while the plasma contents of UMP, carnitine, N-formylanthranilic acid, and adenosine were decreased significantly. The pathway analysis indicated that therapeutic dose of lipid-soluble alkaloids of FZ could regulate energy and amino acid metabolic disorders in AIA rats. However, toxic dose could cause bile acid, fat, amino acid, and energy metabolic disorders. And combination with total glucosides of peony could enhance the therapeutic effects and attenuate the toxicity induced by lipid-soluble alkaloids of FZ.
| S-EPMC6442482 | biostudies-literature
Project description: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.
| S-EPMC7189569 | biostudies-literature
Project description:Background:Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain. Methods:RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data. Results:Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of "meridian tropism" in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory. Conclusions:Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.
| S-EPMC7245909 | biostudies-literature
Project description:Chinese herbs have long been used to treat allergic disease, but recently the development was greatly impeded by the lack of good methods to explore the mechanism of action. Here, we showed the effects of Chinese herb Radix Paeoniae alba were identified and characterized by a mast cell activation assay that involves electronic impedance readouts for dynamic monitoring of cellular responses to produce time-dependent cell responding profiles (TCRPs), and the anti-allergic activities were further confirmed with various conventional molecular and cell biology tools. We found Radix P. alba can dose-dependently inhibit TCPRs, and have anti-allergic function in vitro and in vivo. Radix P. alba suppressed mast cell degranulation not only inhibiting the translocation of granules to the plasma membrane, but also blocking membrane fusion and exocytosis; and that there may be other anti-allergic components in addition to paeoniflorin. Our results suggest that Radix P. alba regulated mast cell activation with multiple targets, and this approach is also suitable for discovering other mast cell degranulation-targeting Chinese herbs and their potential multi-target mechanisms.
| S-EPMC4873249 | biostudies-literature
Project description:Restless legs syndrome (RLS) is a neurological motor disorder with a high prevalence. The treatment efficacy of RLS is unsatisfactory. Radix Paeoniae Alba (RPA) can effectively treat RLS symptoms such as the discomfort of the legs. RPA has great potential for the development of new medications for RLS. Hence, we explored the mechanism of RPA in the treatment of RLS using network pharmacology and molecular docking. The active components and targets of RPA were obtained from the Traditional Chinese Medicine System Pharmacology database and analysis platform and PharmMapper platform. The RLS-related targets were found in GeneCards, OMIM, DrugBank, and DisGeNET databases. The overlapping targets of RPA and RLS were then collected. The "active components-overlapping targets" network was built, and network topology analysis was performed. Furthermore, Cytoscape 3.9.1 software was used to screen the key components of RPA in the treatment of RLS. Protein-protein interaction was performed using the Search Tool for the Retrieval of Interacting Genes. The gene ontology functions and Kyoto Encyclopedia of Genes and Genomes signaling pathways were analyzed using ClusterProfiler, PathView, and other R packages to reveal the main mechanism of RPA in treating RLS. Component and protein structures were downloaded from the Traditional Chinese Medicine System Pharmacology and Protein Data Bank databases, respectively. The AutoDock 4.2.6 software was used for molecular docking. A total of 12 active components and 109 targets of RPA, as well as 2387 RLS-related targets, were collected. Following that, 47 overlapping targets were obtained. Furthermore, 5 key components and 12 core targets were screened. The results of gene ontology functions were as follows: 2368 biological processes, 264 molecular functions, and 164 cellular components. A total of 207 Kyoto Encyclopedia of Genes and Genomes signaling pathways were obtained, including the lipid and atherosclerosis pathway, the endocrine resistance pathway, the prolactin signaling pathway, and the IL-17 signaling pathway. The components and the core targets completed molecular docking stably. RPA has multi-component, multi-target, and multi-pathway characteristics in treating RLS, which could provide a basis for future research and improve clinical efficacy.
| S-EPMC9678500 | biostudies-literature