Abstract

In recent years, many traditional Chinese medicine injections based on Panax notoginseng saponin (PNS) have been reported to cause anaphylaxis. Previous studies on the anaphylactic saponins of PNS and their mechanism are inadequate. In this study, potential anaphylactic saponins were obtained by the separation of PNS and preparation of each individual component through comprehensive techniques, such as liquid chromatography, preparative chromatography, HPLC, NMR, and MS. The anaphylactic abilities of these saponins were tested using RBL-2H3 cells via a β-hexosaminidase release rate test. The results for the mechanism of anaphylaxis were obtained by a proteomic analysis using RBL-2H3 cells. The results indicate that, among all the saponins prepared, gypenoside LXXV and notoginsenoside T5 showed strong anaphylactic abilities and notoginsenoside ST-4 and ginsenoside Rk3 showed weak anaphylactic abilities. These 4 saponins can induce anaphylaxis via direct stimulation of effector cells. The gene oncology enrichment analysis results showed that, among these saponins, only gypenoside LXXV was related to organelles of the endoplasmic reticulum and Golgi apparatus and biological processes in response to organic cyclic compounds. Four proteins in RBL-2H3 cells with the accession numbers A0A0G2JWQ0, D3ZL85, D4A5G8, and Q8K3F0 were identified as crucial proteins in the anaphylactic process. This research will help traditional Chinese medicine injection manufacturers strengthen their quality control and ensure the safety of anaphylactic saponins.

Highlights

  • IntroductionTraditional Chinese medicine (TCM) injection, an innovative form of drug therapy, has become increasingly popular [1, 2]

  • Over the past decade, traditional Chinese medicine (TCM) injection, an innovative form of drug therapy, has become increasingly popular [1, 2]

  • According to related adverse drug reaction (ADR) reports, the ADR rate of TCM injections has risen in the past several years [3]

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Summary

Introduction

Traditional Chinese medicine (TCM) injection, an innovative form of drug therapy, has become increasingly popular [1, 2]. Xu et al [5, 10] studied the anaphylactoid reaction induced by Xuesaitong injection and discovered that >10 kDa molecules could activate classical complement pathways through direct stimulation to cause anaphylaxis; Tween-80 can activate the complement system through classical and alternative pathways; and tannic acid can induce anaphylactoid reactions through coactivation of the complement system, the kallikrein-kinin system, and coagulation. Another mechanism is direct stimulation, which occurs through either direct G protein activation or opioid receptors [7]. Some TCM injections can directly induce β-hexosaminidase and histamine release through mast cell degranulation [7]

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