Histamine H1 receptor cell membrane chromatography online high‐performance liquid chromatography with mass spectrometry method reveals houttuyfonate as an activator of the histamine H1 receptor

Allergy is an abnormal reaction of the body to an allergen. Histamine is responsible for many of the acute symptoms of allergic diseases. Many of the allergic and inflammatory actions of histamine are mediated by the histamine H1 receptor. In the present study, we established a two‐dimensional histamine H1 receptor/cell membrane chromatography with online high‐performance liquid chromatography and mass spectrometry method for screening potential histamine‐activating components in a traditional Chinese medicine injection. The specification of the method was validated by screening, separating, and identifying a mixed standard solution of diphenhydramine hydrochloride, gefitinib, tamsulosin, and nitrendipine. The Yujin injection, an example of traditional Chinese medicine injection, was screened and potential allergic components acting on the histamine H1 receptor were identified. A Ca²⁺ flux assay showed that houttuyfonate and Yujin injection induced calcium release in a dose‐dependent manner. This suggests that houttuyfonate is an activator of the histamine H1 receptor. The mechanism of houttuyfonate activation involves phosphorylation of the inositol‐1,4,5‐trisphosphate receptor. In conclusion, this two‐dimensional method can rapidly detect and enrich target components isolated from the Yujin injection. This indicates that individuals with an overexpression of the histamine H1 receptor should be aware of possible allergic reactions when receiving the Yujin injection.