Model-based fed-batch cultivation of Viola odorata plant cells exhibiting antimalarial and anticancer activity
R, B.; Veeramani, M.; Aadinath, W.; Muthuvijayan, V.; Singh, S.; Srivastava, S.
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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
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