Combined Cornus Officinalis and Paeonia Lactiflora Pall Therapy Alleviates Rheumatoid Arthritis by Regulating Synovial Apoptosis via AMPK-Mediated Mitochondrial Fission.
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ABSTRACT:
SUBMITTER: Huang L
PROVIDER: S-EPMC8062904 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cornus officinalis Sieb et. Zucc and Paeonia lactiflora Pall. have exhibited favorable therapeutic effects against rheumatoid arthritis (RA), but the specific mechanisms of their active compounds remain unclear. The aim of this study was to comprehensively analyze the therapeutic mechanisms of selected active compounds in Cornus officinalis (loganin, ursolic acid, and morroniside) and Paeonia lactiflora (paeoniflorin and albiflorin) via network pharmacology. The pharmacological properties of the five active compounds were evaluated and their potential target genes were identified by database screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analysis were performed to determine the enriched molecular pathways associated with the active compounds. Using network pharmacology tools, eight genes (IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3) were identified as common targets between RA and the five active compounds. Molecular docking simulation revealed the compound-target relationship between the five active compounds and three selected targets from the eight common ones (LGALS3, STAT3, and VEGFA). The compound-target relationships were subsequently validated via preliminary in vivo experiments in a rat model of collagen-induced arthritis. Rats subjected to collagen-induced arthritis showed increased protein expression of LGALS3, STAT3, and VEGFA in synovial tissues. However, treatment using Cornus officinalis or/and Paeonia lactiflora, as well as their most drug-like active compounds (ursolic acid or/and paeoniflorin, respectively, identified based on pharmacological properties), attenuated the expression of these three targets, as previously predicted. Collectively, network pharmacology allowed the pharmacological and molecular roles of Cornus officinalis and Paeonia lactiflora to be systematically revealed, further establishing them as important candidate drugs in the treatment and management of RA.
| S-EPMC8097135 | biostudies-literature
Project description:The complete chloroplast genome sequence of Paeonia lactiflora was obtained by de novo assembly using next-generation sequencing. The circular molecule of the genome constituted of four parts, with 152,731?bp in the complete chloroplast genome, including a large single-copy (LSC) region of 84,402?bp, a small single-copy (SSC) region of 16,969?bp, and two inverted repeat (IRa and IRb) regions of 25,680?bp each. The genome annotation predicted a total of 111 genes, including 77 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis showed the close taxonomical relationship to P. veitchii.
| S-EPMC7706810 | biostudies-literature
Project description:Paeonia lactiflora has been listed as an Endangered species in Russian Federation. The complete plastome was assembled from Next-Generation Sequencing data. It is 152,747?bp in length. It consists of a pair of Inverted Repeat regions (25,651?bp), separated by a small single copy region of 17,033?bp and a large single copy region of 84,412?bp. The plastome encoded 128 genes, including 83 protein coding genes, 37 tRNA, eight rRNA genes, four pseudogenes, and is characterized by loss of the rpl32 and infA genes. Phylogenetic analysis of Paeoniaceae plastomes revealed that P. lactiflora clustered with Eurasian peonies (section Paeoniae).
| S-EPMC7799943 | biostudies-literature
Project description:Stem bending caused by mechanical failure is a major constraint for high-quality herbaceous peony (Paeonia lactiflora Pall.) cut flowers, but little is known about the underlying factors. In this study, two P. lactiflora cultivars, Xixia Yingxue (bending) and Hong Feng (upright), were used to investigate differences in stem bending. The results showed that the stem mechanical strength of Hong Feng was significantly higher than that of Xixia Yingxue, and the thickening of the secondary cell wall and the number of thickened secondary cell wall layers in Hong Feng were significantly higher than those in Xixia Yingxue. Moreover, compared with Xixia Yingxue, Hong Feng showed greater lignification of the cell wall and lignin deposition in the cell walls of the sclerenchyma, vascular bundle sheath and duct. All three types of lignin monomers were detected. The S-lignin, G-lignin, and total lignin contents and the activities of several lignin biosynthesis-related enzymes were higher in Hong Feng than in the other cultivar, and the S-lignin content was closely correlated with stem mechanical strength. In addition, 113,974 full-length isoforms with an average read length of 2106 bp were obtained from the full-length transcriptome of P. lactiflora stems, and differential expression analysis was performed based on the comparative transcriptomes of these two cultivars. Ten lignin biosynthesis-related genes, including 26 members that were closely associated with lignin content, were identified, and multiple upregulated and downregulated transcription factors were found to positively or negatively regulate lignin biosynthesis. Consequently, lignin was shown to provide mechanical support to P. lactiflora stems, providing useful information for understanding the formation of P. lactiflora stem strength.
| S-EPMC7769982 | biostudies-literature
Project description:Chalcone isomerase gene (CHI) is a key gene that regulates the formation of yellow traits in petals. To reveal transcriptional regulatory mechanisms of CHI gene in petals of Paeonia lactiflora, we investigated the CHI expression using qPCR, the pigment content by HPLC, and methylation levels using BSP+Miseq sequencing in 'Huangjinlun' variety during different developmental stages including flower-bud stage (S1), initiating bloom (S2), bloom stage (S3), and withering stage (S4). Results showed that the expression level of CHI gene at S2 stage was significantly higher than that at other stages (P<0.05), and at S4 stage was extremely significantly lower than other stages (P<0.01). Besides, total anthocyanin, anthoxanthin, and flavonoid contents in petals presented a similar trend with CHI expression during developmental stages. A total of 16 CpG sites varying methylation levels were detected in CHI gene core promoter region, of which the methylation levels at mC-4 and mC-16 sites were extremely significantly negatively correlated with CHI mRNA expression (P<0.01). mC-16 site is located in the binding region of C/EBP? transcription factor, suggesting that methylation at the mC-16 site may inhibit the binding of C/EBP? to CHI promoter DNA, thereby regulating the tissue-specific expression of CHI gene. Our study revealed the expression pattern of CHI gene in petal tissues of P. lactiflora at different developmental stages, which is related to promoter methylation. Moreover, the important transcription regulation element-C/EBP? was identified, providing theoretical reference for in-depth study on the function of CHI gene in P. lactiflora.
| S-EPMC6137250 | biostudies-literature
Project description:The herbaceous peony (Paeonia lactiflora Pall.) is a well-known ornamental flowering and pharmaceutical plant found in China. Its high medicinal value has long been recognized by traditional Chinese medicine (as Radix paeoniae Alba and Radix paeoniae Rubra), and it has become economically valued for its oilseed in recent years; like other Paeonia species, it has been identified as a novel resource for the ?-linolenic acid used in seed oil production. However, its genome has not yet been sequenced, and little transcriptome data on Paeonia lactiflora are available. To obtain a comprehensive transcriptome for Paeonia lactiflora, RNAs from 10 tissues of the Paeonia lactiflora Pall. cv Shaoyou17C were used for de novo assembly, and 416,062 unigenes were obtained. Using a homology search, it was found that 236,222 (approximately 57%) unigenes had at least one BLAST hit in one or more public data resources. The construction of co-expression networks is a feasible means for improving unigene annotation. Using in-house transcriptome data, we obtained a co-expression network covering 95.13% of the unigenes. Then we integrated co-expression network analyses and lipid-related pathway genes to study lipid metabolism in Paeonia lactiflora cultivars. Finally, we constructed the online database HpeNet (http://bioinformatics.cau.edu.cn/HpeNet) to integrate transcriptome data, gene information, the co-expression network, and so forth. The database can also be searched for gene details, gene functions, orthologous matches, and other data. Our online database may help the research community identify functional genes and perform research on Paeonia lactiflora more conveniently. We hope that de novo transcriptome assembly, combined with co-expression networks, can provide a feasible means to predict the gene function of species that do not have a reference genome.
| S-EPMC7641121 | biostudies-literature
Project description:The MYB transcription factor (TF) is crucial for plant growth, development, and response to abiotic stress, but it is rarely reported in the herbaceous peony (Paeonia lactiflora Pall.). Here, an MYB TF gene was isolated, and based on our prior mRNA data from P. lactiflora samples, it was treated with drought stress (DS). Its complete cDNA structure was 1314 bp, which encoded 291 amino acids (aa). Furthermore, using sequence alignment analysis, we demonstrated that PlMYB108 was an R2R3-MYB TF. We also revealed that PlMYB108 was primarily localized in the nucleus. Its levels rose during DS, and it was positively correlated with drought tolerance (DT) in P. lactiflora. In addition, when PlMYB108 was overexpressed in tobacco plants, the flavonoid content, antioxidant enzyme activities, and photosynthesis were markedly elevated. Hence, the transgenic plants had stronger DT with a higher leaf water content and lower H2O2 accumulation compared to the wild-type (WT) plants. Based on these results, PlMYB108 is a vital gene that serves to increase flavonoid accumulation, reactive oxygen species (ROS), scavenging capacity, and photosynthesis to confer DT. The results would provide a genetic resource for molecular breeding to enhance plant DT.
| S-EPMC8584830 | biostudies-literature
Project description:BackgroundPaeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway.Materials and methodsLiquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico.ResultsFour major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression.ConclusionThe potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.
| S-EPMC4562737 | biostudies-literature
Project description:Herbaceous peony (Paeonia lactiflora Pall.), one of the world's most important ornamental plants, is highly susceptible to Botrytis cinerea, and improving resistance to this pathogenic fungus is a problem yet to be solved. MicroRNAs (miRNAs) play an essential role in resistance to B. cinerea, but until now, no studies have been reported concerning miRNAs induction in P. lactiflora. Here, we constructed and sequenced two small RNA (sRNA) libraries from two B. cinerea-infected P. lactiflora cultivars ("Zifengyu" and "Dafugui") with significantly different levels of resistance to B. cinerea, using the Illumina HiSeq 2000 platform. From the raw reads generated, 4,592,881 and 5,809,796 sRNAs were obtained, and 280 and 306 miRNAs were identified from "Zifengyu" and "Dafugui", respectively. A total of 237 conserved and 7 novel sequences of miRNAs were differentially expressed between the two cultivars, and we predicted and annotated their potential target genes. Subsequently, 7 differentially expressed candidate miRNAs were screened according to their target genes annotated in KEGG pathways, and the expression patterns of miRNAs and corresponding target genes were elucidated. We found that miR5254, miR165a-3p, miR3897-3p and miR6450a might be involved in the P. lactiflora response to B. cinerea infection. These results provide insight into the molecular mechanisms responsible for resistance to B. cinerea in P. lactiflora.
| S-EPMC4584336 | biostudies-literature
Project description:Herbaceous peony (Paeonia lactiflora Pall.) is popular worldwide because of its gorgeous flower colour, and the yellow flower is the rarest. However, its mechanism of yellow formation is still unexplored from the post-translational level. In this study, the anatomy of the petal, cell sap pH and metal elements were investigated in bicoloured flower cultivar 'Jinhui' with red outer-petal and yellow inner-petal, and the yellow formation was influenced by the anatomy of petal, while not by the cell sap pH and metal elements. Subsequently, microRNAs sequencing (miRNA-seq) was used to identify small RNAs (sRNAs). A total of 4,172,810 and 3,565,152 specific unique sRNAs were obtained, 207 and 204 conserved miRNAs and 38 and 42 novel miRNAs were identified from red outer-petal and yellow inner-petal, respectively, which were confirmed by subcloning. Among these miRNAs, 163 conserved and 28 novel miRNAs were differentially expressed in two wheel of petals. And 5 differentially expressed miRNAs and their corresponding target genes related to yellow formation were screened, and their dynamic expression patterns confirmed that the yellow formation might be under the regulation of miR156e-3p-targeted squamosa promoter binding protein-like gene (SPL1). These results improve the understanding of miRNA regulation of the yellow formation in P. lactiflora.
| S-EPMC5357961 | biostudies-literature