Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase‐9/2 in mice

Fan, Yixin; Hu, Liang; Zhu, Suhua; Han, Yuan; Liu, W.‐t.; Yang, Yanjing; Li, Q.‐p.

doi:10.1002/ejp.1116

Cited by 30 publications

(14 citation statements)

References 53 publications

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“…While (+)-naloxone is inactive at opioid receptors, one of the main sites of interaction of the immune system with persistent pain has been identified as neuro-immune crosstalk at the glial-opioid interface [12, 13]. Indeed, glial cells are involved in opioid actions [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Machine-learned analysis of global and glial/opioid intersection–related DNA methylation in patients with persistent pain after breast cancer surgery

et al. 2019

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BackgroundGlial cells in the central nervous system play a key role in neuroinflammation and subsequent central sensitization to pain. They are therefore involved in the development of persistent pain. One of the main sites of interaction of the immune system with persistent pain has been identified as neuro-immune crosstalk at the glial-opioid interface. The present study examined a potential association between the DNA methylation of two key players of glial/opioid intersection and persistent postoperative pain.MethodsIn a cohort of 140 women who had undergone breast cancer surgery, and were assigned based on a 3-year follow-up to either a persistent or non-persistent pain phenotype, the role of epigenetic regulation of key players in the glial-opioid interface was assessed. The methylation of genes coding for the Toll-like receptor 4 (TLR4) as a major mediator of glial contributions to persistent pain or for the μ-opioid receptor (OPRM1) was analyzed and its association with the pain phenotype was compared with that conferred by global genome-wide DNA methylation assessed via quantification of the methylation in the retrotransposon LINE1.ResultsTraining of machine learning algorithms indicated that the global DNA methylation provided a similar diagnostic accuracy for persistent pain as previously established non-genetic predictors. However, the diagnosis can be based on a single DNA based marker. By contrast, the methylation of TLR4 or OPRM1 genes could not contribute further to the allocation of the patients to the pain-related phenotype groups.ConclusionsWhile clearly supporting a predictive utility of epigenetic testing, the present analysis cannot provide support for specific epigenetic modulation of persistent postoperative pain via methylation of two key genes of the glial-opioid interface.

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Section: Introductionmentioning

confidence: 99%

Machine-learned analysis of global and glial/opioid intersection–related DNA methylation in patients with persistent pain after breast cancer surgery

et al. 2019

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“…It also could inhibit the proliferation of primary and T-HESCs and induce cell cycle arrest of the latter in the G2/M phase in vitro [37]. Paeonia lactifora has hematopoietic functions, anti-in ammatory activity, and immunological properties.In P. lactifora, paeoni orin could inhibit the plantar incision-induced microglia TLR4/MMP-9/2/IL-1β signaling pathway and suppresses postoperative pain [38].…”

Section: Potential Mechanism Of Elc Treatmentmentioning

confidence: 98%

Exploring the Modulatory Mechanism of Eleng Capsule in the Treatment of Endometriosis Based on Integrated Strategy of Transcriptomics Combined With Network Pharmacology

Zheng¹,

Wang²,

Gu³

et al. 2020

Preprint

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BackgroundEndometriosis causes severe chronic pelvic pain and infertility. Chinese medicine plays an active role in the treatment of endometriosis. ELeng Capsule(ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. The previous studies have shown that ELC inhibits endometriosis. However, the mechanisms of action of ELC have not been characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC.Methods Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis(UPLC-Q-TOF/MS) was used to identify the compounds in ELC.And network pharmacology was used to analyze the network of targets and identified compounds of ELC. Apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5'-triphosphate (dUTP) nick-end labeling (TUNEL) assay.The protein expression of VEGFA,VEGFB,VEGFC and α-SMA in the ectopic endometrium were identified by immunohistochemistry(IHC).The level of VEGFA,VEGFB and IL1-β in serum were used by ELISA. Further, RNA-sequencing was used to identify differentially expressed genes (DEGs) in ELC. Biological functions and pathways were determined through the Gene Ontology(GO) and Kyoto encyclopedia of genes and genomes pathway(KEGG) analyses. In addition, Gene Set Enrichment Analysis (GSEA) analysis was used to further analyze the genetic network and modular genetics. ResultsWe had identified 26 new bioactive compounds in ELeng Capsule by UPLC-Q-TOF/MS analysis. The KEGG pathways of ELC associtaed targets related to neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the vascular endothelial growth factor signaling pathway by network pharmacology analysis.Further, ELC could induce cell apoptosis, inhibit angiogenesis through reduce the expression of VEGFA and VEGFC, and inhibit the fibrosis through reduce the expression of α-SMA in ectopic lesions(P＜0.05). In addition, the development of endometriosis in the rat model may be related to mechanisms of inflammation,epithelial-mesenchymal transition(EMT) by RNA-sequencing. And the targets in the treatment of ELC were predominantly associated with actin and cytoskeleton,EMT,focal adhesion,and inflammatory immunity based on the DEGs analysis. In additon, the GSEA analysis showed that the treatment of ELC was associated with the Notch signaling pathway, Hippo signaling pathway, etc.ConclusionELeng Capsules exerted beneficial effects against endometriosis, potentially by induce apoptosis,modulating the angiogenesis,cytoskeleton, epithelial-mesenchymal transition(EMT), and cell junction-associated pathways,etc. These findings could provide evidence for an innovative treatment strategy and novel therapeutic targets for endometriosis.

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“…have been class ifi ed as fl avonoids, hydrolysable tannins (polyphenols), and monoterpene glycosides. Paeoniflorin could inhibit the plantar incisioninduced microglia TLR4/matrix metalloproteinase (MMP-9)/ MMP2/IL-1b signaling pathway and suppress postoperative pain in mice (Fan et al, 2018). Paeoniflorigenone could induce apoptosis and has antiproliferative effects in the cancer cell lines (Huang et al, 2017).Paeonol has a n t i p y r e t i c , a n a l g e s i c , a n t i t u m o r , antioxidation, antiinflammatory, and immunoregulatory properties (Zhang L. et al, 2019).…”

Section: The Combining Rule and Synergy Effects Of Hps And Prescriptionsmentioning

confidence: 99%

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

Zheng

et al. 2020

Front. Pharmacol.

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could also regulate VEGF signaling, toll-like reporter signaling, NF-kB signaling, MAPK signaling, PI3K-Akt signaling, and the HIF-1 signaling pathway, among others. Synergies often exist in herb pairs and herbal prescriptions. In conclusion, we identified some important targets, target pairs, and regulatory networks, using bioinformatics and data mining. The combination of data mining and network pharmacology may offer an efficient method for drug discovery and development from herbal medicines.

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Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase‐9/2 in mice

Cited by 30 publications

References 53 publications

Machine-learned analysis of global and glial/opioid intersection–related DNA methylation in patients with persistent pain after breast cancer surgery

Machine-learned analysis of global and glial/opioid intersection–related DNA methylation in patients with persistent pain after breast cancer surgery

Exploring the Modulatory Mechanism of Eleng Capsule in the Treatment of Endometriosis Based on Integrated Strategy of Transcriptomics Combined With Network Pharmacology

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

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