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This study provides valuable insights into the domestication processes of honeysuckle (Lonicera japonica Thunb.), a semi-evergreen twining vine in the Caprifoliaceae family that is important in traditional Chinese medicine for its flower buds and potential as a dietary supplement. The definition of domestication syndrome for honeysuckle remains unclear due to its perennial and asexual reproduction mode, resulting in a lack of information on domestication-related traits. Therefore, this study aims to compare and analyze differences in morphology, resistance, and biochemical composition between wild and cultivated varieties.