120017
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.6 Breast Cancer (Dove Med Press)
- 4.3 Clin Epidemiol
- 2.6 Cancer Manag Res
- 3.2 Infect Drug Resist
- 4.1 Clin Interv Aging
- 6.1 Drug Des Dev Ther
- 4.1 Int J Chronic Obstr
- 8.7 Int J Nanomed
- 2.5 Int J Women's Health
- 3.2 Neuropsych Dis Treat
- 2.4 OncoTargets Ther
- 2.6 Patient Prefer Adher
- 2.6 Ther Clin Risk Manag
- 3.1 J Pain Res
- 3.5 Diabet Metab Synd Ob
- 4.5 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 2.4 Pharmgenomics Pers Med
- 2.6 Risk Manag Healthc Policy
- 4.6 J Inflamm Res
- 2.3 Int J Gen Med
- 3.9 J Hepatocell Carcinoma
- 3.3 J Asthma Allergy
- 2.5 Clin Cosmet Investig Dermatol
- 3.0 J Multidiscip Healthc
已发表论文
左归丸通过减弱 MAPK 介导的小胶质细胞 M1 极化促进多发性硬化的髓鞘再生：一项整合网络药理学与实验验证研究
Authors Zhao P, Li Y, Li W , Han X, Cheng W , Fan M, Xu L, Han J, Liu X
Received 10 October 2025
Accepted for publication 13 January 2026
Published 5 February 2026 Volume 2026:19 572873
DOI https://doi.org/10.2147/JIR.S572873
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Dharmappa Krishnappa
Peiyuan Zhao,1– 3,* Yihao Li,1,* Wenlu Li,1 Xu Han,1 Wen Cheng,1 Mengyang Fan,1 Liuqing Xu,1 Jingxian Han,4 Xihong Liu1
1Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Collaborative Innovation Center for Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Zhengzhou, Henan, People’s Republic of China; 3Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan, People’s Republic of China; 4The 7th People’s Hospital of Zhengzhou, Zhengzhou, Henan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xihong Liu, Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengdong New District, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86 15810191601, Email lxhong423@hactcm.edu.cn
Purpose: Zuo Gui Wan (ZGW) shows clinical potential in treating multiple sclerosis (MS), but its underlying mechanism of action remains elusive. This study aims to elucidate the efficacy and molecular mechanisms of ZGW in a cuprizone (CPZ)-induced demyelination mouse model.
Methods: Adult male C57BL/6J mice were randomized into four groups (n = 12 each), normal control (NC), CPZ model, CPZ + 2.8 g/kg/d ZGW (ZGW-L), and CPZ + 5.6 g/kg/d ZGW (ZGW-H). Demyelination was induced by a 0.2% CPZ diet for 9 weeks. ZGW or saline was administered intragastrically from weeks 6 to 9. Behavioral performance was assessed using the rotarod, elevated plus-maze, and tail suspension tests. Remyelination was evaluated via LFB staining, TEM, and the expression of oligodendrocyte markers (Olig2, CNPase, MOG). Microglial activation/polarization (Iba-1, iNOS, CD86, Arg-1, CD206) and MAPK pathway proteins (p-ERK1/2, p-p38, and p-JNK) were quantified by Western blot or immunofluorescence. The phytochemical profile of ZGW were analyzed using LC-MS, and target prediction was performed using TCMSP, BATMAN-TCM, and SwissTarget Prediction. Network pharmacology, protein-protein interaction (PPI) analysis, and molecular docking were employed to identify core pathways and targets.
Results: ZGW treatment exhibited a dose-dependent improvement in motor coordination and alleviated anxiety- and depression-like behaviors in CPZ mice. Histological and ultrastructural analyses demonstrated significantly enhanced remyelination and increased expression of Olig2, CNPase, and MOG. Network pharmacology and molecular docking analyses identified the MAPK signaling cascade as the principal therapeutic axis, with key ZGW compounds showing high affinity for MAPK3 and TNF-α. In vivo, ZGW suppressed CPZ-induced phosphorylation of ERK1/2, p38, and JNK, reduced Iba-1 expression and M1 markers (iNOS and CD86), but did not significantly alter Arg-1 or CD206.
Conclusion: ZGW promotes remyelination in CPZ-induced demyelination by inhibiting MAPK pathway overactivation and attenuating microglial M1 polarization, thereby modulating the neuroinflammatory milieu.
Keywords: remyelination, microglial polarization, MAPK signaling pathway, traditional Chinese medicine formula
1Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Collaborative Innovation Center for Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Zhengzhou, Henan, People’s Republic of China; 3Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan, People’s Republic of China; 4The 7th People’s Hospital of Zhengzhou, Zhengzhou, Henan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xihong Liu, Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengdong New District, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86 15810191601, Email lxhong423@hactcm.edu.cn
Purpose: Zuo Gui Wan (ZGW) shows clinical potential in treating multiple sclerosis (MS), but its underlying mechanism of action remains elusive. This study aims to elucidate the efficacy and molecular mechanisms of ZGW in a cuprizone (CPZ)-induced demyelination mouse model.
Methods: Adult male C57BL/6J mice were randomized into four groups (n = 12 each), normal control (NC), CPZ model, CPZ + 2.8 g/kg/d ZGW (ZGW-L), and CPZ + 5.6 g/kg/d ZGW (ZGW-H). Demyelination was induced by a 0.2% CPZ diet for 9 weeks. ZGW or saline was administered intragastrically from weeks 6 to 9. Behavioral performance was assessed using the rotarod, elevated plus-maze, and tail suspension tests. Remyelination was evaluated via LFB staining, TEM, and the expression of oligodendrocyte markers (Olig2, CNPase, MOG). Microglial activation/polarization (Iba-1, iNOS, CD86, Arg-1, CD206) and MAPK pathway proteins (p-ERK1/2, p-p38, and p-JNK) were quantified by Western blot or immunofluorescence. The phytochemical profile of ZGW were analyzed using LC-MS, and target prediction was performed using TCMSP, BATMAN-TCM, and SwissTarget Prediction. Network pharmacology, protein-protein interaction (PPI) analysis, and molecular docking were employed to identify core pathways and targets.
Results: ZGW treatment exhibited a dose-dependent improvement in motor coordination and alleviated anxiety- and depression-like behaviors in CPZ mice. Histological and ultrastructural analyses demonstrated significantly enhanced remyelination and increased expression of Olig2, CNPase, and MOG. Network pharmacology and molecular docking analyses identified the MAPK signaling cascade as the principal therapeutic axis, with key ZGW compounds showing high affinity for MAPK3 and TNF-α. In vivo, ZGW suppressed CPZ-induced phosphorylation of ERK1/2, p38, and JNK, reduced Iba-1 expression and M1 markers (iNOS and CD86), but did not significantly alter Arg-1 or CD206.
Conclusion: ZGW promotes remyelination in CPZ-induced demyelination by inhibiting MAPK pathway overactivation and attenuating microglial M1 polarization, thereby modulating the neuroinflammatory milieu.
Keywords: remyelination, microglial polarization, MAPK signaling pathway, traditional Chinese medicine formula