[Zhuyu Pills restore Th1/Th2 balance mediated by CD1d/iNKT cell axis to alleviate disorders of sebum and blood lipid metabolism].

Authors

Wei Song, Zheng-Wen Teng, Zhong-Yi Zhang, Si-Jie Dang, Tao Shen, Min Xiao, Yong Zhang

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 8. Pages 2286-2294.

Abstract

This study aims to explore the pathogenesis of the comorbidity of atherosclerosis(AS) accompanied by seborrhea and the intervention effect of Zhuyu Pills. A mouse model of AS with seborrhea was constructed by feeding ApoE~(-/-)mice with a high-fat diet for 12 weeks. The 50 successfully modeled ApoE~(-/-)mice were randomly assigned into 5 groups: model, low-dose, medium-dose, and high-dose(130. 54, 261. 08, and 522. 16 mg·kg~(-1), respectively) Zhuyu Pills, and atorvastatin calcium(10. 40 mg·kg~(-1)), with 10 mice in each group. Ten normal C57BL/6J mice were used as the blank control group. The blank control group and the model group were administrated with an equal volume of normal saline by gavage, while the other groups were administrated with corresponding drugs by gavage once a day for 12 weeks. After the administration was completed, hematoxylin-eosin(HE) staining was performed to observe the pathological changes of the aorta and auricle, and the percentage of aortic plaque area and the inflammation score of the auricle were calculated. The levels of total cholesterol(TC), triacylglycerol(TG), low-density lipoprotein cholesterol(LDL-C), and fasting blood glucose( FBG) in the serum were quantified by biochemical methods. The levels of free non-esterified fatty acids(NEFA) and TG in the auricular sebaceous glands were measured by colorimetric methods. The levels of helper T cell 1(Th1)-type pro-inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin(IL)-6], Th2-type anti-inflammatory cytokines(IL-4 and IL-10), and fasting insulin( FINS) in the serum were assessed by enzyme-linked immunosorbent assay( ELISA). The homeostatic model assessment of insulin resistance(HOMA-IR) was calculated. The changes of invariant natural killer T(iNKT) cells in the thymus, spleen, and liver were detected by flow cytometry. The expression of differentiation cluster 1d(CD1d) in the thymus, spleen, and liver was detected by immunohistochemistry. The protein levels of TNF-α, IL-6, IL-4 and IL-10 in the liver were quantified by Western blot. The results showed that compared with the blank control group, the model group exhibited extensive thickening of the aortic intima, an increase in the percentage of aortic plaque area(P<0. 01), extensive infiltration of inflammatory cells in the auricle, an increase in the inflammation score(P<0. 01), elevated levels of TC, TG, LDL-C, and FBG in the serum(P<0. 01) and NEFA, TG in the auricle(P< 0. 01), raised serum levels of TNF-α, IL-6 and an increase in HOMA-IR(P< 0. 01), lowered serum levels of IL-4, IL-10, and FINS(P<0. 01), an increase in CD1d expression in the thymus, spleen, and liver(P<0. 01), an increase in the proportion of iNKT cells(P<0. 01), up-regulation in the protein levels of TNF-α and IL-6(P<0. 01), and down-regulation in the protein levels of IL-4 and IL-10 in the liver(P<0. 01). Compared with the model group, low, medium, and high doses of Zhuyu Pills as well as atorvastatin calcium decreased the enriched area of aortic plaques and the percentage of plaque area(P<0. 01), attenuated the infiltration of inflammatory cells in the auricle, and reduced the inflammation score(P<0. 01), lowered the levels of TC, TG, LDL-C, and FBG in the serum(P<0. 05, P<0. 01) and NEFA, TG in auricular sebaceous glands(P<0. 05, P<0. 01), lowered the serum levels of TNF-α, IL-6 and decreased the HOMA-IR(P<0. 05, P<0. 01), raised the serum levels of IL-4, IL-10, and FINS(P<0. 05, P<0. 01), inhibited the expression of CD1d in the thymus, spleen, and liver(P<0. 01), decreased the proportion of iNKT cells(P<0. 01), down-regulated the protein levels of TNF-α and IL-6(P<0. 01), and up-regulated the protein levels of IL-4 and IL-10 in the liver(P<0. 01). In conclusion, Zhuyu Pills demonstrate definite therapeutic effects on aortic plaques and seborrhea in mice and can alleviate inflammatory responses by regulating the CD1d/iNKT cell axis-mediated Th1/Th2 balance.

PMID:
42392715
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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