Model-based fed-batch cultivation of Viola odorata plant cells exhibiting antimalarial and anticancer activity

Viola odorata is used in the indigenous medicine to treat respiratory tract disorders and is limited in availability. Bioprocess principles can be applied to develop sustainable methods to produce high-quality V. odorata biomass. To this effect, a modified stirred tank reactor and a balloon-type bubble column reactor were used to improve biomass production. Nutrient feeding strategies were developed using first principle-based mathematical modelling to achieve higher cell density in the reactor. Experimental validation of the fed-batch model-predicted strategy resulted in a two-fold enhancement in biomass production (32.2 g DW L-1) at the bioreactor level. Also, bioreactor-cultivated biomass extracts were tested for in vitro hemolytic, cytotoxic, anti-inflammatory, and in vivo antiplasmodial activities. This is the first report on fed-batch cultivation in bioreactors and the antiplasmodial activity of V. odorata. Overall, the bioactive potential of the in vitro-generated biomass extracts is found to be similar to that in the natural plant biomass extracts. HighlightsO_LICultivation of V. odorata cell suspension culture using a modified stirred tank and balloon-type bubble column bioreactors. C_LIO_LIBatch kinetic models were developed and extrapolated into a fed-batch model. C_LIO_LIEnhanced biomass production (32.2 g DW L-1) in bioreactors using a nutrient-feeding strategy. C_LIO_LIExtracts showed anti-inflammatory effects and up to 80 % inhibition of parasite growth, with no hemolytic activity. C_LIO_LIConfirmed antiplasmodial activity in vivo, effective alongside artesunate. C_LIO_LIIn vitro-generated biomass extracts showed comparable bioactive potential to that of natural plants. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/618783v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@171c39aorg.highwire.dtl.DTLVardef@1e0eda5org.highwire.dtl.DTLVardef@121eddorg.highwire.dtl.DTLVardef@1a86215_HPS_FORMAT_FIGEXP M_FIG C_FIG