Toxicological evaluation of ginsenoside-rich cell culture biomass of Panax japonicus produced in a large-scale bioreactor system

Bioreactor Systems for Plant Cell Cultivation at the Institute of Plant Physiology of the Russian Academy of Sciences: 50 Years of Technology Evolution from Laboratory to Industrial Implications

“…6 and 7, Table 1) for plant cell suspension cultivation. Our studies confirmed that these bioreactors were the most favorable for the cultivation of undifferentiated plant cells and had fewer disadvantages compared to bioreactors of other types [21,80,[87][88][89][90].…”

“…The maximum duration of semi-continuous cultivation in the industrial bioreactor reached 170 days. During the scaling up of the cultivation process to industrial volumes, all strains maintained an active synthesis of target metabolites (ginsenosides, furostanol-type glycosides, triterpene glycosides of the oleanane type, and taxanes) at a sufficiently high level, mostly corresponding to those recorded for flask cultures [21,87,171,172]. A minor decrease in the productivity of secondary metabolites and a reduction in all physiological parameters was observed only for the pilot (75 L) bioreactor with a single point sparger combined with mechanical agitation, which was likely due to cell culture response to intense shear stress.…”

“…In our studies, this problem was approached by stepwise analysis of the critical parameters reflecting the physiological state of plant cell cultures at all stages of the upscaling process, from flasks to industrial bioreactors. The development and optimization of the technology for the industrial cultivation of suspension cell cultures was mainly focused on Dioscorea deltoidea, Polyscias filicifolia, Panax japonicus, and Taxus wallichiana [21,[87][88][89]124,169]. For these cell cultures, changes in growth dynamics and the accumulation of secondary metabolites between the different stages of the upscaling process (Figure 4) were identified and critically analyzed.…”

“…The semi-continuous cultivation was selected for upscaling as the most flexible and productive regime both in terms of biomass and secondary metabolite yield (Table 2). Bubble-type bioreactors (total volume 20-630 L, Figure 4) were chosen for the upscaling scheme based on the highest growth and biosynthetic characteristics of the cell strains observed in this type of bioreactors [83,87,88,124]. Bioreactors with a 20 L volume were inoculated directly from flasks.…”

“…Triterpene glycosides of the oleanane type: PFS, ladyginoside A, polysciosides A-E Bioreactor-produced cell biomass has documented adaptogenic and anti-teratogenic activities and is currently used in commercial food supplements [89,174,175] *-upscaling scheme as in The cell biomass of Dioscorea deltoidea and Panax japonicus produced in industrial bioreactors contained essential macro-(K, Ca, Mg, Na) and micro-(Zn, Mn, Fe, B, Al, Cu) elements in dietary safe concentrations [21,87]. Toxicology analysis on in vivo models revealed little or no effect of the cell biomass of these cultures on the animal state, organ weights, and the hematological and biochemical parameters of the blood [21,87]. Phytopreparations based on the cell culture extracts of bioreactor-produced P. japonicus, D. deltoidea, and Tribulus terrestris L. also demonstrated positive effects in rats with induced type 2 diabetes mellitus and diet-induced obesity [171,172].…”