Enhancing the anti-inflammatory efficacy of polysaccharides through processing techniques: a case study on <i>Atractylodes macrocephala</i>

The dried rhizome of <i>Atractylodes macrocephala</i> Koidz., or Bai-Zhu, is commonly used in Traditional Chinese Medicine (TCM) for its gastrointestinal and metabolic benefits. The processing of Bai-Zhu with Aurantii Fructus Immaturus (AFI) enhances its therapeutic effects, though the underlying molecular mechanisms remain unclear. This study compared the chemical composition and bioactivity of AFI-processed Bai-Zhu polysaccharides (ABZP) and unprocessed Bai-Zhu polysaccharides (BZP). Chemical analysis showed that AFI processing increased polysaccharide yield with minimal changes in molecular weight and structure. In the activity evaluation, both BZP and ABZP improved insulin sensitivity and reduced lipid accumulation, with ABZP exhibiting stronger anti-inflammatory effects in C2C12 myotubes. Mechanistic studies indicated that ABZP modulated the PI3K/Akt and NF-κB pathways, enhancing anti-inflammatory responses. Moreover, proteomic analysis reveals that ABZP induces a more refined and potentially safer molecular response compared to BZP. These findings highlight the importance of traditional processing in optimising therapeutic outcomes for metabolic and inflammatory disorders.