Cinnacassdiol, a novel anti-inflammatory phenylpropanoid from Cinnamomum cassia barks: Insights from an integrated in vitro, in vivo and in silico investigation

Inflammation is acknowledged as a pivotal factor in numerous health problems. Cinnamomum cassia , a classic plant with both medicinal and culinary value, is highly recognized for its significant anti-inflammatory properties. In this study, an undescribed phenylpropanoid-glycosyl derivative, named cinnacassdiol ( CCD ) was obtained from the barks of C. cassia and structurally characterized using a combination of HR-ESI-MS, NMR and quantum calculation of optical rotation (OR). Anti-inflammatory evaluation revealed that CCD significantly inhibited excessive neutrophil migration in multiple zebrafish models. Molecular docking combined with molecular dynamic (MD) simulations prompted the strong binding affinities and favorable energetical stabilization of CCD toward the protein domains of IL-6, TNF- α , IκB α and NF-κB. This prediction was validated in LPS-stimulated zebrafish and RAW 264.7 cell models at both mRNA and protein levels. Overall, this study identified a novel compound from C. cassia and established a robust scientific basis for its development as an anti-inflammatory functional food ingredient. • An undescribed phenylpropanoid-glycosyl derivative, cinnacassdiol ( CCD ), was isolated and structurally characterized from the barks of Cinnamomum cassia . • CCD exhibited distinct anti-inflammatory activities both in vitro and in vivo . • CCD significantly inhibited the expressions of inflammatory cytokines IL-6, TNF-α, IκB α and NF-κB at both mRNA and protein levels. • CCD could be a promising candidate to serve as a functional food ingredient.