Exploring the biological tissue toxicity and related toxic components of Euodiae Fructus through the multi-tissue spectrum-toxicity relationship.

Abstract

Euodiae Fructus is recorded in ancient Chinese herbal texts as having "small toxicity", with "soup washing" noted as a detoxification method. However, the specific organs affected and the conditions required for detoxification remain unclear. This study systematically evaluated the toxicity of Euodiae Fructus on serum and various organs (liver, heart, spleen, lung, kidney, and brain) and clarified the parameters of hot-water washing. Decoction components were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), with the fingerprint peak areas from various decoctions constituting the spectral profile. The total relative levels of the serum toxicity index and tissue injury indices were defined as "toxicity." A spectral-toxicity relationship was established using partial least squares regression, from which regression equations, coefficients, and variable importance in projection were obtained. Toxicity analysis indicated that Euodiae Fructus primarily affects the liver, spleen, lung, kidney, and brain. Moreover, rapid hot-water washing performed three times significantly reduced its toxicity. A total of 32 toxic compounds were identified, predominantly including alkaloids, triterpenes, organic acids, volatile oils, and flavonoids. These findings provide an experimental basis for the rational use of Euodiae Fructus and offer methodological insights for the pharmacological investigation of traditional Chinese medicine.