Transformation of ginsenoside Rh4 and its aglycone from the total saponins of stems and leaves of Panax ginseng by Aspergillus tubingensis.

Graphical abstract Highlights • Rare ginsenosides were successfully bio-transformed by Aspergillus tubingensis. • Rh4 aglycone increased over 100 folds than that in the original TSSLG. • MCL-1 was explored as anticancer target of Rh4 and its aglycone. Abstract 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. [ABSTRACT FROM AUTHOR]