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

Circadian Pharmacological Effects of Paeoniflorin on Mice With Urticaria-like Lesions.
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芍药苷对荨麻疹样病变小鼠的昼夜药理作用

DOI:
10.3389/fphar.2021.639580
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发表时间:
2021
影响因子:
5.6
通讯作者:
Zeng J
Zeng J
中科院分区:
医学2区
文献类型:
--
作者:
Peng L;Wen L;Zhang J;Zhang X;Wei Q;Guo J;Zeng J

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芍药苷 (PF) 是一种具有多种生物学特性的单萜葡萄糖苷,可抑制荨麻疹样病变 (UL) 大鼠模型的过敏和炎症反应。在本研究中,我们在四个昼夜节律时间点(ZT22、ZT04、ZT10 和 ZT16)对 OVA 诱导出现 UL 的小鼠进行 PF 治疗,以确定 PF 的最佳给药时间。通过分析抓挠行为评估PF的药理作用;组织病理学特征;过敏反应,例如免疫球蛋白 E (IgE)、白三烯 B4 (LTB4) 和组胺 (HIS) 释放;炎症细胞浸润[肥大细胞类胰蛋白酶(MCT)和嗜酸性粒细胞蛋白X(EPX)];炎症细胞因子的 mRNA 水平,例如白细胞介素 (IL)-12、IL-6、干扰素-γ (IFN-γ) 和 IL-4。结果表明,PF显着减轻抓挠行为和组织病理学特征,ZT10给药是四个昼夜节律时间点中缓解病情最有效的时间点。此外,PF 降低了 IgE、LTB4 和 HIS 的血清水平,并且在 ZT10 时给予 PF 产生了相对优越的效果。 PF 治疗,尤其是 ZT10 剂量,显着减少了 UL 小鼠皮肤组织中肥大细胞和颗粒的数量,并减少了 MCT 和 EPX 的浸润。此外,口服PF可有效降低IL-12 mRNA的炎症细胞因子水平。总之,PF的不同给药时间影响其对UL小鼠的疗效。 ZT10给药表现出相对优越的疗效,可能是治疗荨麻疹的最佳给药时间。
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.
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