Structure–Activity Differences of Chlorogenic Acid and Its Isomers on Sensitization via Intravenous Exposure

Abstract

Chlorogenic acid (CGA) is found in many plants that are used as medicinal substances in traditional Chinese medicine injectables (TCMIs). However, to date, there is controversy as to whether CGA is the major cause of TCMIs-related hypersensitivity administered intravenously. Therefore, the aim of this study was to evaluate the potential sensitization of CGA and structure-activity differences between its isomers using an intravenous exposure mouse model. The results showed that popliteal lymph nodes proliferation was significantly induced by CGA and its isomers. Both CGA and isochlorogenic acid A (iso-CGA A) significantly enhanced the secretion of trinitrophenyl (TNP) ovalbumin-specific immunoglobulin (Ig)G1; and iso-CGA B significantly induced TNP-specific IgG1, IgM, and IgG2b secreting. Furthermore, the results of quantitative structure-activity relationship analysis suggested that chemical structure factors, including atomic mass, electronegativity, atom shape and size, atom distribution, atomic weight, and atomic polarizabilities, the ionic currents, were significantly correlated with the potential sensitization of CGA and its isomers. In summary, when administered intravenously, the strength and type of sensitization may be correlated with structure differences in the CGA family.

Prediction of allergic reaction risk of Shenmai injection based on real‐world evidence coupled with UPLC–Q‐TOF‐MS

“…In the hapten hypothesis of drug hypersensitivity, the critical step is the formation of adducts (drug–protein conjugates) (Lin, Gong, et al, 2012). Organic acids are parent components that are highly reactive toward nucleophiles.…”

“…According to statistics, more than 90% of CHI‐induced AR cases were related to CHI containing organic acids, and most clinicians considered organic acids as the cause of allergic diseases (Lin, Gong, et al, 2012). In addition, an intravenous mouse model showed that organic acids were potential sensitizers, which triggered immune‐mediated drug hypersensitivity by significantly enhancing the secretion of IgE (Lin, Sun, et al, 2012).…”

RhoA/ROCK Signaling Pathway Mediates Shuanghuanglian Injection-Induced Pseudo-allergic Reactions

“…Most clinicians considered chlorogenic acid as the chief culprit as its antigenic properties were identified since 1960s ( Freedman et al, 1961 ; Freedman, 1964 ). In addition, most of the adverse reactions related to Chinese medicinal injections seemed to be because of chlorogenic acid containing preparations ( Lin et al, 2012 , 2013 ). Previous studies demonstrated that chlorogenic acid and its conversion product-cryptochlorogenic acid could directly evoke mast cell degranulation and β-hexosaminidase release, triggering pseudo-allergic reactions ( Huang et al, 2010 ; Li et al, 2013 ; Wang et al, 2015 ).…”

Evaluation of the Potential Sensitization of Chlorogenic Acid: A Meta-Analysis

“…In this work, two studies were included in meta-analysis of PLNA parameters; one proved a positive reaction by using an intravenous mouse model [14, 35], while another showed a negative result by subcutaneous administration. The inconsistent results of PLN cellularity and IgG1 AFCs were pooled by meta-analysis and the pooled results showed that CGA might significantly increase PLN cellularity and induce IgG1 AFCs formation.…”