Search

Chrysin, one of the most pharmacologically active natural flavonoids, has been extracted from various plants. Mast cells are an important part of innate immunity-mediating anaphylaxis. Pseudo-allergic reactions are currently believed to be associated with the MAS-related GPR family member X2 (MrgX2). In this study, the anti-pseudo allergy effect of chrysin and its underlying mechanisms were studied in vitro and in vivo. Chrysin inhibited passive cutaneous anaphylaxis and systemic pseudo-allergy in vivo. LAD2 cell degranulation, calcium ion (Ca2+) influx, and adenosine 5'-triphosphate (ATP) content were significantly suppressed in a dose-dependent manner. Chrysin suppressed pseudo-allergic reactions through the PLC/IP3/Ca2+ and ERK/STAT3 serine 727 pathways downstream of MrgX2. Therefore, mitochondrial ATP, but not glycolysis, is vital for pseudo-allergic reactions mediated by MrgX2. This study provides new insights for the treatment of pseudo-allergy.

The outbreak of coronavirus disease 2019 (COVID‐19) has induced a large number of deaths worldwide. Angiotensin‐converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019‐nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID‐19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019‐nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the K D value of (4.33 ± 0.09) e−8, (6.29 ± 1.12) e−6, (2.37 ± 0.59) e−5, and (4.85 ± 1.57) e−5 M, respectively. But only ZDV and EFV prevent the 2019‐nCoV spike pseudotyped virus to enter ACE2‐HEK293T cells with an EC50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019‐nCoV infection of ACE2‐HEK293T cells by interacting with ACE2.

Licochalcone A (Lico A) is a natural flavonoid belonging to the class of substituted chalcone that has various biological effects. Mast cells (MCs) are innate immune cells that mediate hypersensitivity and pseudo-allergic reactions. MAS-related GPR family member X2 (MRGPRX2) on MCs has been recognized as the main receptor for pseudo-allergic reactions. In this study, we investigated the anti-pseudo-allergy effect of Lico A and its underlying mechanism. Substance P (SP), as an MC activator, was used to establish an in vitro and in vivo model of pseudo-allergy. The in vivo effect of Lico A was investigated using passive cutaneous anaphylaxis (PCA) and active systemic allergy, along with degranulation, Ca2+ influx in vitro. SP-induced laboratory of allergic disease 2 (LAD2) cell mRNA expression was explored using RNA-seq, and Lico A inhibited LAD2 cell activation by reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence staining. Lico A showed an inhibitory effect on SP-induced MC activation and pseudo-allergy both in vitro and in vivo. The nuclear factor (NF)-κB pathway is involved in MRGPRX2 induced MC activation, which is inhibited by Lico A. In conclusion, Lico A inhibited the pseudo-allergic reaction mediated by MRGPRX2 by blocking NF-κB nuclear migration.