Table3_Circadian Pharmacological Effects of Paeoniflorin on Mice With Urticaria-like Lesions.xlsx

Paeoniflorin (PF) is a monoterpene glucoside with various biological properties, and it suppresses allergic and inflammatory responses in a rat model of urticaria-like lesions (UL). In the present study, we treated OVA-induced mice presenting UL with PF at four circadian time points (ZT22, ZT04, ZT10, and ZT16) to determine the optimal administration time of PF. The pharmacological effects of PF were assessed by analyzing the scratching behavior; histopathological features; allergic responses such as immunoglobulin E (IgE), leukotriene B4 (LTB4), and histamine (HIS) release; inflammatory cell infiltration [mast cell tryptase (MCT) and eosinophil protein X (EPX)]; and mRNA levels of inflammatory cytokines such as interleukin (IL)-12, IL-6, interferon-γ (IFN-γ), and IL-4. It was demonstrated that PF significantly alleviated scratching behavior and histopathological features, and ZT10 dosing was the most effective time point in remission of the condition among the four circadian time points. Moreover, PF decreased the serum levels of IgE, LTB4, and HIS, and PF administration at ZT10 produced relatively superior effectiveness. PF treatment, especially dosing at ZT10, significantly reduced the number of mast cells and granules and diminished the infiltration of MCT and EPX in the skin tissues of mice with UL. Furthermore, the oral administration of PF effectively decreased the inflammatory cytokine levels of IL-12 mRNA. In conclusion, different administration times of PF affected its efficacy in mice with UL. ZT10 administration demonstrated relatively superior effectiveness, and it might be the optimal administration time for the treatment of urticaria.

芍药苷（Paeoniflorin, PF）是一类具有多种生物活性的单萜葡萄糖苷（monoterpene glucoside），可在荨麻疹样损伤（urticaria-like lesions, UL）大鼠模型中抑制过敏与炎症反应。本研究针对卵清蛋白（OVA）诱导的UL模型小鼠，于四个昼夜授时时辰点（ZT22、ZT04、ZT10、ZT16）给予PF干预，旨在明确PF的最优给药时辰。本研究通过分析小鼠的搔抓行为、组织病理学特征、过敏反应指标（包括免疫球蛋白E（IgE）、白三烯B4（LTB4）、组胺（HIS）释放水平）、炎症细胞浸润情况[肥大细胞类胰蛋白酶（MCT）与嗜酸性粒细胞蛋白X（EPX）表达]，以及白细胞介素（IL）-12、IL-6、干扰素-γ（IFN-γ）、IL-4等炎症细胞因子的mRNA表达水平，对PF的药理学效应进行评估。研究结果显示，PF可显著改善小鼠的搔抓行为与组织病理学异常，四个给药时辰中，ZT10给药的病情缓解效果最为显著。此外，PF可降低小鼠血清中IgE、LTB4与HIS的水平，且ZT10给药的干预效果相对最优。PF处理，尤其是ZT10给药方式，可显著减少UL模型小鼠皮肤组织中的肥大细胞数量与脱颗粒颗粒，并降低MCT与EPX的浸润程度。进一步研究发现，口服PF可有效下调IL-12 mRNA的炎症细胞因子表达水平。综上，PF的不同给药时辰会影响其对UL模型小鼠的治疗效能，其中ZT10给药展现出相对最优的干预效果，或为荨麻疹治疗的最佳给药时辰。