Abstract
Apigenin (API) is a natural phytoestrogen with properties including anti-inflammatory and other abilities. This study aims to 1) systematically validate that excessive estrogen exacerbates allergic reactions; 2) explore the anti-allergic effects and mechanisms of API. We conduct a survey of college students, indicating that of the 505 effective results, 70 individuals were self-reported allergic and 74.1% of them were women, which proved the gender difference in allergic reactions. BALB/c mice are grouped into the negative control group (N-Ctrl), the OVA-sensitized group (P-Ctrl), the estrogenized OVA-sensitized group (E2), and three treatment groups administrating different dose of API (E2 + API/L/M/H). In vivo data indicated that API treatment significantly inhibited the enhancement of estradiol on clinical symptoms. Moreover, we found that high doses of API inhibited Th2 type humoral response and mast cell degranulation levels in vivo and in vitro. Additionally, medium, and high doses of API significantly reduced the potentiation of estradiol on ER expression, attenuated the transmission of estrogen/ER signaling, thereby inhibiting the phosphorylation of ERK1/2 and JNK1/2/3 in the MAPK. Besides, we found that API competitively bound to ER with estradiol, and showed a weak selectivity to ERβ. Overall, we identified API can be beneficial in allergic disease.
Highlights
Food allergy refers to a hypersensitivity disorder in which the immune system abnormally reacts to non-infectious environmental substances (Galli et al, 2008), often induces a series of allergic disease complications, such as urticaria, asthma, and diarrhea, which could seriously affect quality of life (Ballegaard et al, 2019)
Our study demonstrated that excess E2 induced the enhancement of allergic reactions in vivo and in vitro, while API showed the opposite effects
As shown in GRAPHICAL ABSTRACT, the main mechanisms of anti-allergic effect of API are summarized as followed: API (1) regulates the Th cell differentiation, which decreased the elevated level of Th2-related cytokine to restore Th1/Th2 immune balance; (2) affects the OVA-specific antibody producing by B cells; (3) inhibits the degranulation of mast cells and the release of inflammatory cytokines through inhibiting MAPK signaling pathway by competitively binding ER with E2
Summary
Food allergy refers to a hypersensitivity disorder in which the immune system abnormally reacts to non-infectious environmental substances (Galli et al, 2008), often induces a series of allergic disease complications, such as urticaria, asthma, and diarrhea, which could seriously affect quality of life (Ballegaard et al, 2019). It has been recognized by the World Health Organization (WHO) as a major global food safety issue (Wang et al, 2019) and seriously affected about as many as 10% of children globally (Abrams et al, 2020). The compound which can inhibit mast cell degranulation (Mwakalukwa et al, 2019) or release of inflammatory cytokines is considered to have anti-allergic activity
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