Rare ginsenoside Rh-4 and its aglycone are present in low levels in Panax ginseng. This study focused on achieving ginsenoside Rh-4 and its aglycone by microbial transformation of the total saponins of stems and leaves of P. ginseng (TSSLG). A total of 78 fungal strains isolated from the rhizosphere soil of P. ginseng, and one of them, Aspergillus tubingensis, was found to be capable of biotransformation of TSSLG to ginsenoside Rh4 and its aglycone with high efficiency, especially the content of ginsenoside Rh4 aglycone was enhanced 100 folds over than that in the original TSSLG. Compared with ginsenoside Rg3 (named ShenYi capsule as antitumor drug in China), ginsenoside Rh4 aglycone exhibited stronger antitumor activity against human cancer cell lines SGC-7901, KB-A-1 and HT-1080. The possible biotransformation pathways of ginsenoside Rh4 and its aglycone were speculated according to the chemical structures. The anticancer binding-target, myeloid cell leukemia 1 protein (MCL-1), was explored using molecular docking analysis and the possible combination mechanism was discussed.

antitumor activity, molecular docking, biotransformation, Panax ginseng, ginsenoside, myeloid cell leukemia 1 protein

• Compound ID: 21807
  

  D-Glcp-(1-6)-Subst Subst = Rh4 aglycon = SMILES C/C(C)=C\C\C=C(C)\C3CC[C@@]4(C)C2C{6}[C@H](O)C1C(CC{3}[C@H](O)[C@]1(C)C)C2C{12}[C@@H](O)C34

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  Structure type: oligomer ; 643.4180 [M+Na]+
  C36H60O8
  Trivial name: ginsenoside Rh4
  Compound class: glycoside
  
   
  
  Aspergillus tubingensis CBS 103.12
  CSDB ID 49039 (all data & tools)