College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, Hangzhou, China.
College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, Hangzhou, China.
J Ethnopharmacol. 2024 Nov 15;334:118545. doi: 10.1016/j.jep.2024.118545. Epub 2024 Jul 16.
ETHNOPHARMACOLOGICAL RELEVANCE: Qinghao-Biejia herb pair (QB) is the core herb pair of "Jieduquyuziyin prescription" and is one of the commonly used herb pairs for the clinical treatment of systemic lupus erythematosus (SLE). Previous studies have shown that QB reduces the expression of inflammatory cytokines like IL-6 and TNF-α in the serum and kidney of MRL/lpr mice. Additionally, it inhibits the expression of TLR4 and MyD88 in the kidney and aorta and reduces the deposition of renal complement C3 and aortic plaque after treatment. These findings suggest that QB has a preventive and therapeutic effect on lupus rats. AIM OF THE STUDY: This study sought to investigate the mechanisms underlying the anti-SLE combined with atherosclerosis activity of the Qinghao-Biejia herb pair. MATERIALS AND METHODS: Drug targets for QB were identified using the HERB database, while targets associated with SLE and atherosclerosis were retrieved from the GeneCards database. The intersection of these drug and disease targets was then analyzed using a protein-protein interaction (PPI) network with GO and KEGG pathway enrichment analysis. In vivo, apolipoprotein E-deficient (ApoE) mice were induced to develop SLE-AS by intraperitoneal injection of pristane and continued feeding of a high-fat diet. The changes in relevant indexes were observed after 12 weeks of gavage treatment with hydroxychloroquine, QB, Q (Qinghao alone), and B (Biejia alone). Bone marrow-derived macrophages from ApoE mice and Raw 264.7 macrophages were used to explore the mechanisms of QB treatment. RESULTS: The levels of inflammatory cytokines in serum and pathological liver changes in mice were improved to varying degrees in the treatment groups. Additionally, there was a reduction in aortic atheromatous plaque formation and some improvement in cholesterol efflux. Furthermore, QB suppressed the expression of inflammatory cytokines in M1 macrophages, suggesting a role in regulating macrophage polarization. CONCLUSION: QB demonstrates clear efficacy for treating SLE-AS, and its therapeutic mechanism may involve the regulation of macrophage phenotypes by promoting cholesterol efflux.
民族药理学相关性：青蒿-鳖甲药对（QB）是“解毒祛瘀滋阴方”的核心药对，也是临床治疗系统性红斑狼疮（SLE）常用药对之一。既往研究表明，QB 可降低 MRL/lpr 小鼠血清和肾脏中白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）等炎症细胞因子的表达，同时抑制肾脏和主动脉中 TLR4 和 MyD88 的表达，减少肾脏补体 C3 和主动脉斑块的沉积。这些发现提示 QB 对狼疮大鼠具有防治作用。
研究目的：本研究旨在探讨青蒿-鳖甲药对对狼疮合并动脉粥样硬化（SLE-AS）的作用机制。
材料与方法：采用 HERB 数据库鉴定 QB 的药物靶点，从 GeneCards 数据库中检索与 SLE 和动脉粥样硬化相关的靶点，采用蛋白质-蛋白质相互作用（PPI）网络分析这些药物和疾病靶点的交集，并进行 GO 和 KEGG 通路富集分析。体内实验采用腹腔注射角鲨烯诱导载脂蛋白 E 缺陷（ApoE）小鼠发生 SLE-AS，继续给予高脂饮食喂养。经过 12 周的羟氯喹、QB、Q（青蒿）和 B（鳖甲）灌胃治疗后，观察相关指标的变化。采用 ApoE 小鼠骨髓来源的巨噬细胞和 Raw264.7 巨噬细胞探讨 QB 治疗的作用机制。
结果：治疗组小鼠血清中炎症细胞因子水平及肝脏病理改变均得到不同程度改善，主动脉粥样硬化斑块形成减少，胆固醇流出增加。此外，QB 抑制 M1 型巨噬细胞中炎症细胞因子的表达，提示其可能通过调节巨噬细胞表型发挥作用。
结论：QB 对 SLE-AS 具有明确的治疗作用，其治疗机制可能与促进胆固醇流出，调节巨噬细胞表型有关。
Acta Pharmacol Sin. 2016-9
J Neuroinflammation. 2025-8-1
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