Xinyue Zhang

Natural compounds have experienced increasing clinical application, but their association with rapid-onset anaphylactoid reactions (ARs) present a significant challenge to their safe use. These ARs, clinically resembling Type I hypersensitivity, are non-IgE-mediated and involve direct mast cell activation, primarily through the human Mas-related G protein-coupled receptor X2 (MRGPRX2). We computationally screened a natural compound library for MRGPRX2 activation. A human MRGPRX2-expressing cell model was established. Cell viability assays (0–80 μM) were performed to determine appropriate drug concentrations. Compared to the controls, Baohuoside I (10 μM), along with Kaempferol-3-O-rutinoside, Epigallocatechin gallate (EGCG), Isochlorogenic Acid B, Baicalin, Andrographolide, Isorhamnetin, and Dehydroandrographolide (all at 20 μM), significantly increased intracellular calcium flux (p < 0.05) and boosted tryptase and β-hexosaminidase secretion (ELISA) (p < 0.05) in mast cells. Furthermore, the degranulation induced by these compounds was inhibited by the MRGPRX2 inhibitor Z3578 at 20 μM. Neutral red staining was employed to observe cellular morphological changes. Specific compounds capable of mediating ARs through MRGPRX2 activation on mast cells were identified. This contributes to safer and more effective drug use by elucidating the potential triggers of ARs.

In the regulatory market, it is not uncommon for ginseng radix et rhizoma (GR) to be adulterated with panacis quinquefolii radix (PR). Amid the digital transformation, this study puts forward a new method for the identification of GR adulterated with PR. Ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to detect multiple batches of GR and PR to obtain mass spectrometry data. The common ions were isolated from multiple batches of GR and PR, serving as GR and PR’s “ion matrices”. Furthermore, GR and PR’s “ion matrices” were used to eliminate intersecting ion data to extract the top-100 ions as GR and PR “matrix identity cards” (MICs). Then, GR and PR’s MICs were employed as a reference for identification, yielding contrast credibility (CC) as feedback. The results indicated that leveraging the MICs of GR and PR enables efficient and precise digital identification of the two herbs: pure GR showed CC ≥ 95% when matched with GR MIC (≤2% with PR MIC), pure PR showed CC ≥ 93% with PR MIC (≤3% with GR MIC), and non-parametric analysis confirmed significant differences between groups (p < 0.01). Even in 5% PR-adulterated samples, CC ranged from 24% to 28% (avg. 25.8%) when matched with PR MIC, leading to a 26% adulteration detection threshold. Moreover, two adulterated batches were identified among ten GR blind samples, which was consistent with verification via PR-specific pseudo-ginsenoside F₁₁. This research is practically valuable for distinguishing between GR and PR, combating adulteration, and reinforcing GR quality management. It also informs the digital identification of GR via UPLC-QTOF-MS and “MICs”, contributing to the digital quality control of traditional Chinese medicines (TCMs).