Zhuyu Pills restore Th1/Th2 balance via CD1d/iNKT axis, alleviating atherosclerosis and seborrhea in ApoE mice.
Background
The comorbidity of atherosclerosis (AS) and seborrhea presents a significant clinical challenge, often linked to systemic inflammation and metabolic dysfunction. Current treatments for these conditions often target individual symptoms, leaving an unmet need for comprehensive interventions addressing underlying immune and metabolic imbalances. Th1/Th2 immune imbalance, characterized by an overactive pro-inflammatory Th1 response, is implicated in both conditions. Furthermore, invariant natural killer T (iNKT) cells, regulated by CD1d molecules, play a crucial role in modulating this immune balance and influencing lipid metabolism, making them a promising therapeutic target.
Study Design
Researchers constructed a mouse model of atherosclerosis with seborrhea by feeding ApoE~(-/-) mice a high-fat diet for 12 weeks. 50 successfully modeled mice were randomized into 5 groups: model, low-dose (130.54 mg/kg), medium-dose (261.08 mg/kg), and high-dose (522.16 mg/kg) Zhuyu Pills, and atorvastatin calcium (10.40 mg/kg). A blank control group of 10 normal C57BL/6J mice was also included. All treatments were administered by gavage once daily for 12 weeks. Primary endpoints included aortic and auricle pathology via HE staining, serum lipids (TC, TG, LDL-C), FBG, auricular sebaceous gland NEFA and TG via colorimetric methods, serum cytokines (TNF-α, IL-6, IL-4, IL-10) and FINS via ELISA, HOMA-IR calculation, iNKT cell changes via flow cytometry, and CD1d expression via immunohistochemistry.
Results
Zhuyu Pills effectively alleviated both atherosclerosis and seborrhea in the high-fat diet-fed ApoE mice. Treatment with Zhuyu Pills significantly reduced the percentage of aortic plaque area and the inflammation score of the auricle compared to the model group. Furthermore, Zhuyu Pills improved systemic metabolic parameters, decreasing serum levels of total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG). The intervention also mitigated local sebaceous gland dysfunction, reducing free non-esterified fatty acids (NEFA) and TG levels in the auricular sebaceous glands. Critically, Zhuyu Pills restored the Th1/Th2 immune balance, implying a reduction in pro-inflammatory Th1-type cytokines like TNF-α and IL-6, and an increase in anti-inflammatory Th2-type cytokines such as IL-4 and IL-10. This beneficial effect was mediated by modulating invariant natural killer T (iNKT) cells and differentiation cluster 1d (CD1d) expression in immune organs. While the abstract strongly indicates these positive outcomes, specific quantitative results (e.g., exact percentages of reduction, p-values) were not provided within the abstract text itself. > Zhuyu Pills restored Th1/Th2 immune balance and modulated iNKT cells and CD1d expression, leading to significant alleviation of atherosclerosis and seborrhea in ApoE mice.
Why It Matters
This study highlights Zhuyu Pills as a potential multi-target therapeutic for the complex interplay between atherosclerosis and seborrhea, conditions often co-occurring with metabolic dysregulation. The finding that it restores Th1/Th2 balance via the CD1d/iNKT axis suggests a novel immunomodulatory mechanism, moving beyond symptomatic relief to address underlying inflammatory drivers. For individuals experiencing both lipid metabolism disorders and skin issues, this traditional Chinese medicine offers a holistic approach. While preclinical, these results open avenues for exploring natural compounds that can simultaneously impact cardiovascular health and dermatological conditions. Further research is needed to translate these findings into human protocols, but it underscores the potential for immune-modulating strategies in complex metabolic diseases.