Novel Antileukemic Active Constituent in a Unique Sichuan Pepper Called "Dingtan hua jiao"

A unique Sichuan pepper derived from Zanthoxylum planispinum var. dintanensis, Dingtan hua jiao, is both edible and has medicinal functions. Although Dingtan hua jiao has been enjoyed as a condiment, its medicinal value has not been clarified. By using modern natural product research techniques, 16 novel tetrahydrofuran lignans (1-16), Zanplanispines A-P, along with 20 known compounds (17-36), were isolated from Dingtan hua jiao of Guizhou Province, China. The structures and absolute configurations of the compounds were determined by comprehensive spectral analyses, including infrared (IR) spectroscopy, ultraviolet (UV) spectroscopy, high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, and theoretical electronic circular dichroism (ECD) calculations. The toxicity of most of the obtained compounds was evaluated against the HL-60 cell line. The results showed that 11 natural lignans inhibited the proliferation of HL-60 cells to varying degrees, especially compound 3, which had the greatest inhibitory effect (IC₅₀ of 9.95 μmol/L). Further mechanistic studies revealed that compound 3 could induce HL-60 cell cycle arrest in the S phase and apoptosis, revealing that Dingtan hua jiao, and especially some of its chemical components, might have very important medicinal value for leukemia treatment.