Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel

Liu, Zhanli1; Shan, Zhiming1,2; Yang, Haoyi1,3; Xing, Yanmei1; Guo, Weijie3; Cheng, Jing1; Jiang, Yuanxu1; Cai, Song3; Wu, Chaoran1; Liu, Jessica Aijia4; Cheung, Chi Wai2; Pan, Yunping5

2024-06-01

10.1213/ANE.0000000000006730

ANESTHESIA AND ANALGESIA   影响因子和分区

0003-2999

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). Schr & ouml;dinger 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 Nav channel 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-alpha (normalized mRNA level mean +/- SEM: LPS [8. 93 +/- 0.78] vs LPS + quercetin [3. 77 +/- 0.49], P < .0001). CONCLUSIONS:Identifying Nav as 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.

SCI

英语

第一

National Natural Science Foundation of China["82001188","82201376"] ; Science and Technology Planning Project of Shenzhen[JCYJ20190807154401665] ; Medical Scientific and Technology Foundation of Guangdong Province[C2022117] ; Natural Science Foundation of Guangdong Province[2021A1515011129] ; Shenzhen Science and Technology Innovative Program[20200812143116001] ; Sanming Project of Medicine in Shenzhen[SZSM202011021]

Anesthesiology

Anesthesiology

WOS:001283151000019

LIPPINCOTT WILLIAMS & WILKINS

CLINICAL MEDICINE

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Anesthesiol, Shenzhen, Peoples R China
2.Univ Hong Kong, Lab & Clin Res Inst Pain, Li Ka Shing Fac Med, Sch Clin Med,Dept Anaesthesiol, Hong Kong, Peoples R China
3.Shenzhen Univ, Hlth Sci Ctr, Shenzhen, Peoples R China
4.City Univ Hong Kong, Dept Neurosci, Hong Kong, Peoples R China
5.Shenzhen Stomatol Hosp, Dept Periodontol & Oral Mucosa, 70 Guiyuanbei Rd, Shenzhen 518022, Peoples R China

Liu, Zhanli,Shan, Zhiming,Yang, Haoyi,et al. Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel[J]. ANESTHESIA AND ANALGESIA,2024,138(6).

Liu, Zhanli.,Shan, Zhiming.,Yang, Haoyi.,Xing, Yanmei.,Guo, Weijie.,...&Pan, Yunping.(2024).Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel.ANESTHESIA AND ANALGESIA,138(6).

Liu, Zhanli,et al."Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel".ANESTHESIA AND ANALGESIA 138.6(2024).