Caffeic acid phenethyl ester inhibits pseudo-allergic reactions via inhibition of MRGPRX2/MrgprB2-dependent mast cell degranulation

Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner

“…Differences between LPS-treated and control groups were considered statistically significant at a level where the p-value was below 0.05. Statistical significance used the two-part Student t-test or One-Way Variance Analysis (ANOVA), as described previously [43], to determine statistical significance using the SPSS17.0 software system (IBM, Chicago, IL, USA). Differences between LPS-treated and control groups were considered statistically significant at a level where the p-value was below 0.05.…”

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

“…Exogenous ligands of MRGPRX2 include the cationic polymer compound 48/80 (C48/80), which is commonly used in receptor functional assays, and a variety of drugs approved by the Food and Drug Administration (FDA), such as fluoroquinolones (e.g., ciprofloxacin), neuromuscular blocking agents (e.g., rocuronium, atracurium), opioids (e.g., morphine), and many others [ 4 , 9 , 28 ]. MRGPRX2 can also be activated or inhibited by other exogenous agents, such as bacterial quorum sensing proteins, insect venoms [ 3 , 29 , 30 ], or many different plant xenobiotics ( Figure 1 ) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]; representatives of which are described in the following part of this review.…”

“…Interestingly, the authors also performed a molecular docking study, in which they demonstrated that rosmarinic acid interacts with MRGPRX2 and associates with its G proteins at the intracellular site ( Figure 3 ) [ 72 ]. Conversely, another study [ 40 ] indicated that rosmarinic acid is a weak inhibitor (IC 50 = 1.8 mM) of C48/80-induced activation of MCs. However, the study was conducted in other cell lines, namely primary cell culture of mouse peritoneal mast cells (MPMC) and MRGPRX2-HEK293 cells, and the concentration of rosmarinic acid used in the study were significantly lower (10 µM versus 25–100 µM in the previous studies), which could have a big impact on data results.…”

“…However, the study was conducted in other cell lines, namely primary cell culture of mouse peritoneal mast cells (MPMC) and MRGPRX2-HEK293 cells, and the concentration of rosmarinic acid used in the study were significantly lower (10 µM versus 25–100 µM in the previous studies), which could have a big impact on data results. Additionally, the study did not provide additional evidence supporting weak performance of rosmarinic acid on MC activation [ 40 ]. On the other hand, the authors also performed molecular docking and showed that rosmarinic acid was not expected to interact with the MRGPRX2 binding pocket [ 40 ].…”

“…Additionally, the study did not provide additional evidence supporting weak performance of rosmarinic acid on MC activation [ 40 ]. On the other hand, the authors also performed molecular docking and showed that rosmarinic acid was not expected to interact with the MRGPRX2 binding pocket [ 40 ]. In conclusion, additional studies should be conducted to elucidate the effect of rosmarinic acid on MRGPRX2-mediated MC functions.…”