Codonopsis pilosula polysaccharide alleviates rotenone-induced murine brain organoids death through downregulation of gene body DNA methylation modification in the ZIC4/PGM5/CAMTA1 axis
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SUBMITTER: Chen H
PROVIDER: S-EPMC10698575 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:BackgroundCodonopsis pilosula (Franch.) Nannf. is one of the most widely used medicinal plants. Although chemical and pharmacological studies have shown that codonopsis polysaccharides (CPPs) are bioactive compounds and that their composition is variable, their biosynthetic pathways remain largely unknown. Next-generation sequencing is an efficient and high-throughput technique that allows the identification of candidate genes involved in secondary metabolism.Principal findingsTo identify the components involved in CPP biosynthesis, a transcriptome library, prepared using root and other tissues, was assembled with the help of Illumina sequencing. A total of 9.2 Gb of clean nucleotides was obtained comprising 91,175,044 clean reads, 102,125 contigs, and 45,511 unigenes. After aligning the sequences to the public protein databases, 76.1% of the unigenes were annotated. Among these annotated unigenes, 26,189 were assigned to Gene Ontology categories, 11,415 to Clusters of Orthologous Groups, and 18,848 to Kyoto Encyclopedia of Genes and Genomes pathways. Analysis of abundance of transcripts in the library showed that genes, including those encoding metallothionein, aquaporin, and cysteine protease that are related to stress responses, were in the top list. Among genes involved in the biosynthesis of CPP, those responsible for the synthesis of UDP-L-arabinose and UDP-xylose were highly expressed.SignificanceTo our knowledge, this is the first study to provide a public transcriptome dataset prepared from C. pilosula and an outline of the biosynthetic pathway of polysaccharides in a medicinal plant. Identified candidate genes involved in CPP biosynthesis provide understanding of the biosynthesis and regulation of CPP at the molecular level.
| S-EPMC4342239 | biostudies-literature
Project description:Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer's disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.
| S-EPMC6277749 | biostudies-literature
Project description:Aging is a biological process that leads to the progressive deterioration and loss of physiological functions in the human body and results in an increase in morbidity and mortality, and aging-related disease is a major global problem that poses a serious threat to public health. Polysaccharides have been shown to delay aging by reducing oxidative damage, suppressing inflammatory responses, and modulating intestinal microbiota. Our previous studies have shown that polysaccharide CPP-1 extracted from the root of Codonopsis pilosula possesses noticeable anti-oxidant activity in vitro. Thus, in our study, we tested the anti-aging effect of CPP-1 in naturally aging mice (in vivo). Eighteen C57/BL mice (48-week-old, male) were divided into a control group, high-dose CPP-1 group (20 mg/mL), and low-dose CPP-1 group (10 mg/mL). We discovered that CPP-1 can exert a reparative effect on aging stress in the intestine and liver, including alleviating inflammation and oxidative damage. We revealed that CPP-1 supplementation improved the intestinal microbiota composition and repaired the intestinal barrier in the gut. Furthermore, CPP-1 was proved to modulate lipid metabolism and repair hepatocyte injury in the liver by influencing the enterohepatic axis associated with the intestinal microbiota. Therefore, we concluded that CPP-1 prevents and alleviates oxidative stress and inflammatory responses in the intestine and liver of aging mice by modulating the intestinal microbiota-related gut-liver axis to delay aging.
| S-EPMC10525188 | biostudies-literature
Project description:Four new acetylenes (1-4) and one new unsaturated ω-hydroxy fatty acid (5), together with 5 known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradecenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of 1 was assigned by comparison of the experimental circular dichroism (CD) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher׳s method based on the MPA determination rule of Δδ RS values for diols.
| S-EPMC4629234 | biostudies-literature
Project description:BackgroundNon-small cell lung cancer (NSCLC) represents a prevalent and challenging malignancy, often posing difficulties in treatment due to late-stage diagnosis and limited therapeutic options.ObjectiveThis study aims to elucidate the impact of Codonopsis pilosula polysaccharide (CPP) on NSCLC, exploring its potential anticancer molecular mechanisms.Materials and methodsPurchase A549 cells and treat them with varying concentrations of CPP, dividing them into groups. Use CCK-8 assays for cell proliferation and TUNEL assays for apoptosis detection. Perform Western blot (WB) to detect NF-κB p65, pNF-κB p65, and pyroptosis-related proteins. Measure ROS, inflammatory factors, and LDH levels using kits. Observe pyroptosis morphology under a microscope. Inoculate A549 cells subcutaneously into nude mice to create a xenograft model and treat them with daily CPP injections. Collect tumor tissues, measure tumor volume and mass. Perform TUNEL immunohistochemistry for apoptosis and H&E staining for tumor histology. Detect pyroptosis-related proteins with Western blot and immunohistochemistry, and assess inflammatory factors using ELISA and immunohistochemistry.ResultsThe research reveals a concentration-dependent inhibitory effect of CPP on A549 cell viability, with optimal efficacy observed at 40 μmol/L CPP. CPP demonstrates the capacity to induce apoptosis, mediate NF-κB activation, and accumulate reactive oxygen species (ROS). Notably, CPP promotes pyroptosis in A549 cells and in vivo, upregulating pyroptosis-related proteins. In vivo administration of CPP significantly inhibits tumor growth, accompanied by notable morphological and histological alterations. Additionally, both in vitro and in vivo studies confirm elevated levels of IL-1β and IL-18 in tumor tissues following CPP treatment.Discussion and conclusionIn conclusion, CPP, as a multifaceted agent, suppresses the progression of NSCLC by inducing NLRP3/GSDMD-dependent pyroptosis. This research provides valuable insights into the therapeutic potential of CPP and stimulates further exploration for its integration into future NSCLC treatments.
| S-EPMC11442958 | biostudies-literature
Project description:Codonopsis Radix (CR) is an important traditional Chinese medicine used for the treatment of spleen deficiency syndrome (SDS). Codonopsis pilosula polysaccharides (CPP) in CR are considered to be responsible for tonifying the spleen function; however, the mechanisms of the polysaccharides have remained unclear. This study aimed to investigate the treatment mechanisms of CPP in SDS mice using a combinational strategy of 16S rRNA gene sequencing and targeted metabolomics. Here, studies demonstrated that CPP had invigorating effect in vivo in Sennae Folium-induced SDS in mice by organ indexes, D-xylose determination, gastrointestinal hormones levels and goblet cells observation. Antibiotic treatment revealed that the intestinal microbiota was required for the invigorating spleen effect of CPP. Furthermore, gut microbiota analysis found that CPP significantly enriched probiotic Lactobacillus and decreased the abundance of some opportunistic pathogens, such as Enterococcus and Shigella. The metabolic profile analysis of the colonic content revealed that 25 chemicals were altered significantly by CPP, including amino acids, organic acids, fatty acids, carbohydrates and carnitine etc., which are mainly related to "energy conversion" related processes such as amino acids metabolism, tricarboxylic acid cycle, and nitrogen metabolism. Spearman's correlation assays displayed there were strong correlations among biochemical indicators-gut microbiota-metabolomics. In summary, these results provided a new perspective for CPP improving SDS by regulating energy metabolism related bacteria and pathways.
| S-EPMC9086242 | biostudies-literature
Project description:Codonopsis pilosula subsp. tangshen is one of the most important medicinal herbs used in traditional Chinese medicine. Correct identification of materials from C. pilosula subsp. tangshen is critical to ensure the efficacy and safety of the associated medicines. Traditional DNA molecular markers could distinguish Codonopsis species well, so we need to develop super or specific molecular markers. In this study, we reported the plastome of Codonopsis pilosula subsp. tangshen (Oliv.) D.Y. Hong conducted phylogenomic and comparative analyses in the Codonopsis genus for the first time. The entire length of the Codonopsis pilosula subsp. tangshen plastome was 170,672 bp. There were 108 genes in the plastome, including 76 protein-coding genes, 28 transfer RNA (tRNA), and four ribosomal RNA (rRNA) genes. Comparative analysis indicated that Codonopsis pilosula subsp. tangshen had an unusual large inversion in the large single-copy (LSC) region compared with the other three Codonopsis species. And there were two dispersed repeat sequences at both ends of the inverted regions, which might mediate the generation of this inversion. We found five hypervariable regions among the four Codonopsis species. PCR amplification and Sanger sequencing experiments demonstrated that two hypervariable regions could distinguish three medicinal Codonopsis species. Results obtained from this study will support taxonomic classification, discrimination, and molecular evolutionary studies of Codonopsis species.
| S-EPMC9342729 | biostudies-literature
Project description:Three new sesquiterpene glycosides, named codonopsesquilosides A-C (1-3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1-3, their aglycones, and model compounds based on quantum-mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed.
| S-EPMC4724660 | biostudies-literature
