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已发表论文
二氢杨梅素调节神经病理性疼痛和抑郁：与小鼠海马血管内皮生长因子的相关性
Authors Li T , Ye LQ, Liu HF, Chen XH, Wang Y , Chen ZM, Zheng Y , Zeng WX, Li SE, Wan L
Received 30 May 2025
Accepted for publication 22 October 2025
Published 4 February 2026 Volume 2026:19 538350
DOI https://doi.org/10.2147/JIR.S538350
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Ning Quan
Tian Li,1,2 Liu-Qing Ye,1,2 Hua-Feng Liu,1,2 Xiao-Hui Chen,1,2 Yu Wang,1,2 Zuo-Ming Chen,1,2 Yu Zheng,1,2 Wen-Xin Zeng,1,2 Si-En Li,1,2 Li Wan1
1Department of Pain Medicine, The State Key Clinical Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 2Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China
Correspondence: Li Wan, Email wanli5000cn@163.com
Introduction: Neuropathic pain (NP) is a multidisciplinary problem of medicine, psychology, sociology and economics. The emotional disorders caused by neuropathic pain are seriously underestimated. The dynamic interaction between the NP and emotional disorders greatly increasing the difficulty in clinical treatment, highlighting the importance of finding an effective treatment for neuropathic pain combined with depression. Dihydromyricetin (DHM) has been shown to be effective in improving neurological diseases due to its potent anti-inflammatory and neuroprotective effects.
Methods: In this study, through network pharmacology and bioinformatics, the potential targets and signaling pathways of DHM in the treatment of neuropathic pain (NP) and depression (DP) comorbidities were predicted. Further animal experiments utilized the spared nerve injury (SNI) model in mice. Mice received daily intraperitoneal injections of DHM (20 mg kg− 1) or vehicle for 14 days. Mechanical sensitivity was assessed with the paw withdrawal mechanical threshold (PWMT), and depressive-like behaviors were assessed by tail suspension test immobility time, open field test total distance moved and central time. Hippocampal levels of vascular endothelial growth factor (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), IL-1β, and TNF-α were quantified by Western blot and immunofluorescence staining.
Results: VEGFA was found to have the high “degree” value after ranking by target correlation based on the analysis from network pharmacology. SNI model evoked persistent the pain and depressive-like behavior that were paralleled by marked hippocampal down-regulation of VEGFA/VEGFR2 and a concomitant surge in IL-1β and TNF-α. However, the pain and depressive-like behavior can be relieved by DHM treatment. Both VEGFA and VEGFR2 were up-regulated in the hippocampus, and the changes of IL-1β and TNF-α were improved after DHM treatment.
Discussion: This study elucidates that DHM alleviates neuropathic pain and depressive-like behavior, potentially be related to the upregulation of the VEGFA/VEGFR2 signaling pathway and subsequent attenuation of neuroinflammation.
Keywords: neuropathic pain, depression, vascular endothelial growth factor
1Department of Pain Medicine, The State Key Clinical Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 2Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China
Correspondence: Li Wan, Email wanli5000cn@163.com
Introduction: Neuropathic pain (NP) is a multidisciplinary problem of medicine, psychology, sociology and economics. The emotional disorders caused by neuropathic pain are seriously underestimated. The dynamic interaction between the NP and emotional disorders greatly increasing the difficulty in clinical treatment, highlighting the importance of finding an effective treatment for neuropathic pain combined with depression. Dihydromyricetin (DHM) has been shown to be effective in improving neurological diseases due to its potent anti-inflammatory and neuroprotective effects.
Methods: In this study, through network pharmacology and bioinformatics, the potential targets and signaling pathways of DHM in the treatment of neuropathic pain (NP) and depression (DP) comorbidities were predicted. Further animal experiments utilized the spared nerve injury (SNI) model in mice. Mice received daily intraperitoneal injections of DHM (20 mg kg− 1) or vehicle for 14 days. Mechanical sensitivity was assessed with the paw withdrawal mechanical threshold (PWMT), and depressive-like behaviors were assessed by tail suspension test immobility time, open field test total distance moved and central time. Hippocampal levels of vascular endothelial growth factor (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), IL-1β, and TNF-α were quantified by Western blot and immunofluorescence staining.
Results: VEGFA was found to have the high “degree” value after ranking by target correlation based on the analysis from network pharmacology. SNI model evoked persistent the pain and depressive-like behavior that were paralleled by marked hippocampal down-regulation of VEGFA/VEGFR2 and a concomitant surge in IL-1β and TNF-α. However, the pain and depressive-like behavior can be relieved by DHM treatment. Both VEGFA and VEGFR2 were up-regulated in the hippocampus, and the changes of IL-1β and TNF-α were improved after DHM treatment.
Discussion: This study elucidates that DHM alleviates neuropathic pain and depressive-like behavior, potentially be related to the upregulation of the VEGFA/VEGFR2 signaling pathway and subsequent attenuation of neuroinflammation.
Keywords: neuropathic pain, depression, vascular endothelial growth factor