Treatment of Liuwei Dihuang Decoction in Experimental Autoimmune Encephalomyelitis in Mice Through TLR4/NF-κB Path-way
10.16466/j.issn1005-5509.2025.09.002
- VernacularTitle:六味地黄汤通过TLR4/NF-κB途径治疗小鼠实验性自身免疫性脑脊髓炎
- Author:
Xiang LIN
1
;
Zhengxia LIU
1
;
Youquan TU
1
Author Information
1. 宁波大学附属妇女儿童医院 宁波 315012
- Publication Type:Journal Article
- Keywords:
experimental autoimmune encephalomyelitis;
multiple sclerosis;
Liuwei Dihuang Decoction;
T lymphocyte subsets;
TLR4/NF-κB signaling pathway;
neurological functional impairment scores;
IL-1β;
IL-6
- From:
Journal of Zhejiang Chinese Medical University
2025;49(9):1094-1104
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To elucidate the role and molecular mechanisms of Liuwei Dihuang Decoction(LWDHD)in the treatment of experimental autoimmune encephalomyelitis(EAE).[Methods]Sixty male C57BL/6 mice were randomly divided into normal group,model group,positive control group[prednisone acetate(PA)],LWDHD low-dose group(7.7 g·kg-1),medium-dose group(15.4 g·kg-1)and high-dose group(30.8 g·kg-1).Mice EAE model was established by using myelin oligodendrocyte glycoprotein 35-55(MOG 35-55)combined with pertussis toxin(PTX)and tuberculin.The mice in LWDHD groups were given LWDHD by gavage for 20 consecutive days,and the mice in positive control group were given PA of 6 mg·kg-1 by gavage.Neurological damage was evaluated by neurological functional impairment scores,hematoxylin-eosin(HE)staining was used to detect pathological changes in brain tissue,interleukin-1β(IL-1β)and interleukin-6(IL-6)levels were detected by enzyme-linked immunosorbent assay(ELISA),and Western blot was utilized to examine the expression of proteins in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway.T lymphocytes were extracted from the spleen of mice and treated with LWDHD containing serum.Flow cytometry was used to evaluate the proportion of CD4+and CD8+T lymphocytes and Western blot was used to detect the effect of LWDHD on the expression of proteins in the TLR4/NF-κB pathway.[Results]Different concentrations of LWDHD significantly improved the neurological function scores in EAE mice(P<0.01),reduced the abnormal proliferation of microglia in the cerebral cortex,and decreased neuronal cell death in the hippocampus.ELISA showed that LWDHD significantly inhibited the secretion of IL-1β and IL-6(P<0.01).Western blot analysis indicated that LWDHD markedly suppressed the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).In cellular experiments,LWDHD containing serum significantly reduced the proportion of CD4+and CD8+T lymphocytes,and inhibited the expression and activation of proteins in the TLR4/NF-κB pathway(P<0.01).[Conclusion]LWDHD significantly inhibits brain inflammatory responses in EAE mice and reduces abnormal proliferation of microglia,which may be associated with the inhibition of protein activation in brain tissue and T lymphocytes via the TLR4/NF-κB pathway.
