2. Academic Validation
  3. Isoliquiritigenin inhibited complete Freund's adjuvant-induced chronic inflammatory pain via the CCL7/CCR2/ERK pathway in dorsal root ganglia neurons of mice

Isoliquiritigenin inhibited complete Freund's adjuvant-induced chronic inflammatory pain via the CCL7/CCR2/ERK pathway in dorsal root ganglia neurons of mice

  • Int Immunopharmacol. 2026 Feb 1:170:116059. doi: 10.1016/j.intimp.2025.116059.
Yi-Min Ren 1,  Yu Chen 2,  Chang-Mao Jiang 3,  Xiong Chen 4,  Hong-Jin Qin 3,  Zhu Wei 3,  Xue Rao 3,  Yu-Chen Wang 3,  Ning-Ze Jiang 3,  Jin-Yuan Luo-Qian 5,  Ying-Nan Song 5,  Xiao-Hua Zou 1,  Jiang Zheng 6,  Hong-Jin Chen 7
Affiliations

Affiliations

  • 1 College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; Guizhou Medical University Key Laboratory of Anesthesia and Pain Mechanism Research, Guizhou Province, Guiyang, 550004, China.
  • 2 College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; School of Basic Medicine, School of Pharmacy, Guizhou Medical University, Guizhou, Guiyang 550004, China; Division of Pain Management, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guizhou Province, Guiyang 550004, China; State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Guizhou Medical University, Guiyang 550004, China.
  • 3 College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang 550004, China.
  • 4 Department of Wound Repair, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
  • 5 Center for Tissue Engineering and Stem Cell Research, Translation Medicine Research Center，Guizhou Biomanufacturing Laboratory, Guizhou Medical University, Guiyang 561113, China.
  • 6 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Guizhou Medical University, Guiyang 550004, China. Electronic address: [email protected].
  • 7 Center for Tissue Engineering and Stem Cell Research, Translation Medicine Research Center，Guizhou Biomanufacturing Laboratory, Guizhou Medical University, Guiyang 561113, China; Department of Pharmacology, School of Basic Medical Sciences, Guizhou Medical University, GuiAn 561113, Guizhou, China. Electronic address: [email protected].
PMID: 41418643 DOI: 10.1016/j.intimp.2025.116059
Abstract

Chronic inflammatory pain (CIP) poses a significant medical challenge, with current pharmacological treatments often associated with considerable side effects. The identification of effective therapeutic targets and the development of novel agents remain major hurdles. Exploring neuroimmune interactions and utilizing network pharmacology to uncover compounds capable of simultaneously modulating pain and inflammation presents a promising strategy. In this study, the therapeutic efficacy, potential targets, and underlying mechanisms of isoliquiritigenin (ISL) were investigated in a mouse model of CIP induced by complete Freund's Adjuvant (CFA) paw pad injection. Single-dose ISL (20 or 60 mg/kg) attenuated CFA-induced hypersensitivity in an acute screening experiment, after which we investigated sustained efficacy using ISL (10 mg/kg) once daily for 7 days. ISL treatment significantly reduced paw swelling, mechanical allodynia, and thermal hyperalgesia. Additionally, ISL lowered the levels of IL-6, TNF-α, and VCAM-1 in both dorsal root ganglia (DRG) and skin tissues, along with a significant reduction in ERK phosphorylation. Network pharmacology analysis and molecular docking suggested CCR2 as a potential target of ISL. Further investigation revealed that ISL attenuated CCL7-induced CCR2 signaling activation. To validate the involvement of CCR2, siRNA-mediated knockdown of CCR2 was performed via DRG injection. This intervention suppressed ISL's analgesic and anti-inflammatory effects in CIP mice and CCL7 paw pad injection-induced pain and inflammation. Moreover, activation of ERK using tert-butylhydroquinone in CCR2 knockdown mice exacerbated CFA-induced inflammatory responses. These findings suggest that ISL alleviates CIP by targeting the CCL7/CCR2 axis and suppressing ERK-mediated inflammation.

Keywords

CCL7; CCR2; Chronic inflammation pain; Dorsal root ganglia neurons; Isoliquiritigenin.

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