The polar high molecular weight fraction of the Agaricus blazei Murill extract, AndoSan™, reduces the activity of the tumor-associated protease, legumain, in RAW 264.7 cells

J Med Food. 2015 Apr;18(4):429-38. doi: 10.1089/jmf.2014.0018. Epub 2014 Aug 19.


AndoSan™ is an extract of Agaricus blazei Murill (AbM; 82.4%), Hericium erinaceum (14.7%), and Grifola frondosa (2.9%). The main ingredient of AndoSan, AbM, is rich in different forms of β-glucans. Since these exhibit potent antitumor activity and have immunomodulatory effects, the stimulatory effect of AndoSan on the production of different cytokines, chemokines, and leukocyte growth factors has predominantly been attributed to β-glucans. AndoSan has been claimed to consist of 90% carbohydrate, of which 2.8% is β-glucans, but in this study, we show that the carbohydrate content is only 2% of the dry weight, corresponding to 0.09% β-glucan per mL of AndoSan. Fractionation of AndoSan, followed by carbohydrate analysis and HPLC analysis revealed that most of the glucose was concentrated in the polar high molecular weight fraction of AndoSan (ethanol insoluble water extract [EIWE]-A) and that this extract was able to significantly inhibit the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform to reach an enzymatically active form. In this study, we demonstrate that both the polar and nonpolar AndoSan fractions are able to inhibit the autoactivation of prolegumain, and that the polar fractions of AndoSan are the most potent inhibitors of the active form of the enzyme.

Keywords: Agaricus brasiliensis; RAW 264.7; legumain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricus / chemistry*
  • Animals
  • Biological Factors / chemistry*
  • Complex Mixtures / chemistry*
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism*
  • Enzyme Inhibitors / chemistry*
  • Kinetics
  • Macrophages / chemistry
  • Macrophages / enzymology*
  • Mice
  • RAW 264.7 Cells
  • beta-Glucans / chemistry


  • AndoSan
  • Biological Factors
  • Complex Mixtures
  • Enzyme Inhibitors
  • beta-Glucans
  • Cysteine Endopeptidases
  • asparaginylendopeptidase