Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Original language | English |
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Pages (from-to) | 1324-1336 |
Journal / Publication | Anesthesia and Analgesia |
Volume | 138 |
Issue number | 6 |
Publication status | Published - Jun 2024 |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85194013026&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(2d05366d-5191-4733-b793-b011d19d0926).html |
Abstract
BACKGROUND: Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment.
METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Nav) channel in rat TG neurons.
RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P =.002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Navchannel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P =.006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P =.034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P <.0001).
CONCLUSIONS: Identifying Navas the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.
© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.
METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Nav) channel in rat TG neurons.
RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P =.002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Navchannel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P =.006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P =.034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P <.0001).
CONCLUSIONS: Identifying Navas the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.
© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.
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Citation Format(s)
Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel. / Liu, Zhanli; Shan, Zhiming; Yang, Haoyi et al.
In: Anesthesia and Analgesia, Vol. 138, No. 6, 06.2024, p. 1324-1336.
In: Anesthesia and Analgesia, Vol. 138, No. 6, 06.2024, p. 1324-1336.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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