Apigenin Attenuates the Allergic Reactions by Competitively Binding to ER With Estradiol

Lu Yao; Zhuoyan Fan; Shiwen Han; Na Sun; Huilian Che

doi:10.3389/fphar.2020.01046

Apigenin Attenuates the Allergic Reactions by Competitively Binding to ER With Estradiol

Front Pharmacol. 2020 Jul 16:11:1046. doi: 10.3389/fphar.2020.01046. eCollection 2020.

Authors

Lu Yao¹, Zhuoyan Fan¹, Shiwen Han¹, Na Sun², Huilian Che¹

Affiliations

¹ Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
² National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, China.

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.

Keywords: MAPK signaling pathway; Th1/Th2 balance; allergic disease; apigenin; estrogen receptor.