Abstract
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.
Highlights
Urticaria is characterized by the rapid appearance of pale to bright wheals, erythema, and pruritus on the skin (Schaefer, 2017)
We explored whether and how the PF exerted effects on histopathological features either in the morning (ZT02) or evening (ZT14) to establish a urticaria-like lesions (UL) mouse model dosed at four circadian time points
After being challenged with OVA/ aluminium hydroxide solution, an obvious scratching reaction was observed in the mice in the OVA and PF groups at all dosing time points as compared with those in the normal control (NC) groups both modeled in the morning (ZT02) and evening (ZT14)
Summary
Urticaria is characterized by the rapid appearance of pale to bright wheals, erythema, and pruritus on the skin (Schaefer, 2017). Immunoglobulin E (IgE) mediates the accumulation and degranulation of mast cells play a Abbreviations: EPX, eosinophil protein X; HIS, histamine; IgE, Immunoglobulin E; IL, interleukin; IOD, integrated optical density; IFN, interferon; i.p, intraperitoneally; LTB4, leukotriene B4; MCT, mast cell tryptase; NC, normal control; OVA, ovalbumin; PF, paeoniflorin; UL, urticaria-like lesions; ZT, zeitgeber time. Circadian Pharmacological Effects of Paeoniflorin central role in the pathogenesis of urticaria, which results in the release of histamine (HIS) and other inflammatory mediators (Church et al, 2018). Urticaria exacerbates nocturnally, displaying changing patterns in symptom attacks during the day and night (Maurer et al, 2009). A safe, effective, selective, and optimal timing of therapy for urticaria has gained attention
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