<p>To address the quality instability of the traditional fermentation process of <i>Massa Medicata Fermentata</i> (LSQ), we designed an innovation strategy for dual-strain co-fermentation LSQ. <i>Rhizopus arrhizus</i>, <i>Bacillus velezensis</i>, <i>Bacillus subtills</i>, and <i>Bacillus cereus</i> were selected as the fermentation strains for the LSQ. After dual-strain co-fermentation, its pro-digestive enzymes and anti-inflammatory activities were significantly enhanced. Particularly, <i>R. arrhizus/B. subtills</i> fermentation group showed the prominent promotion of the enzymatic activities of amyloglucosidase, cellulase and trypsin, with AC200 values &lt; 1.00 and Max fold increase values of 27.39 ± 0.22, 25.39 ± 0.87 and 48.07 ± 1.84, respectively, and anti-inflammatory activity with an IC<sub>50</sub> value of 2.35 ± 0.18 mg/mL. Based on the correlation analysis of differential metabolic profiles and activities, the key pharmacodynamic metabolites were analyzed and validated, such as levomycetin succinatea, <i>β</i>-citrylglutamate, <i>D</i>-glucosaminic acid, nikkomycin and fucose 1-phosphate. Among them, <i>D</i>-glucosaminic acid was positively correlated with the promoting activity of amyloglucosidase, cellulose, enzyme trypsin, pepsin, and the inhibitory activity of NO production, and fucose 1-phosphate and nikkomycin had the prominently positive correlation with the promoting activity of pepsin (<i>p</i> &lt; 0.01). In addition, the docking scores between them and digestive enzyme proteins were all &lt; −&#xa0;5. A new strategy involving the dual-strain fermentation of LSQ was investigated, and clarified the LSQ fermentation strain-constituent-pharmacological activity correlations, which provides a valuable reference for delving into the LSQ fermentation mechanism.</p> Graphical abstract <p></p>

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A new strategy for the fermentation of Massa Medicata Fermentata by combining multiple strains of fermentation and their fermentation mechanisms

  • Wanqiu Liu,
  • Ying Liu,
  • Jie Zhang,
  • Huangyao Zhu,
  • Siqi Fan,
  • Jingwen Ha,
  • Yuxuan Lu,
  • Yizhu Wang,
  • Wenyuan Liu,
  • Ma Mi,
  • Feng Feng,
  • Jian Xu

摘要

To address the quality instability of the traditional fermentation process of Massa Medicata Fermentata (LSQ), we designed an innovation strategy for dual-strain co-fermentation LSQ. Rhizopus arrhizus, Bacillus velezensis, Bacillus subtills, and Bacillus cereus were selected as the fermentation strains for the LSQ. After dual-strain co-fermentation, its pro-digestive enzymes and anti-inflammatory activities were significantly enhanced. Particularly, R. arrhizus/B. subtills fermentation group showed the prominent promotion of the enzymatic activities of amyloglucosidase, cellulase and trypsin, with AC200 values < 1.00 and Max fold increase values of 27.39 ± 0.22, 25.39 ± 0.87 and 48.07 ± 1.84, respectively, and anti-inflammatory activity with an IC50 value of 2.35 ± 0.18 mg/mL. Based on the correlation analysis of differential metabolic profiles and activities, the key pharmacodynamic metabolites were analyzed and validated, such as levomycetin succinatea, β-citrylglutamate, D-glucosaminic acid, nikkomycin and fucose 1-phosphate. Among them, D-glucosaminic acid was positively correlated with the promoting activity of amyloglucosidase, cellulose, enzyme trypsin, pepsin, and the inhibitory activity of NO production, and fucose 1-phosphate and nikkomycin had the prominently positive correlation with the promoting activity of pepsin (p < 0.01). In addition, the docking scores between them and digestive enzyme proteins were all < − 5. A new strategy involving the dual-strain fermentation of LSQ was investigated, and clarified the LSQ fermentation strain-constituent-pharmacological activity correlations, which provides a valuable reference for delving into the LSQ fermentation mechanism.

Graphical abstract