The Hypoglycemic and Hypocholesterolemic Activity of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus Cell Culture Biomass in Rats with High-Fat Diet-Induced Obesity

Abstract

Obesity, and its consequences for human health, is a huge and complicated problem that has no simple solution. The constant search for natural and safe compounds with systemic action that can be used for obesity prophylactics and treatment is hampered by the limited availability and variable quality of biomass of wild medicinal plants. Plant cell biotechnology is an alternative approach for the sustainable production of vegetative biomass or individual phytochemicals with high therapeutic potential. In this study, the suspension cell biomass of the medicinal plants, Dioscorea deltoidea Wall., Tribulus terrestris L., and Panax japonicus (T. Nees) C.A. Mey, produced in 20 L and 630 L bioreactors, were tested for therapeutic effects in rat models with alimentary-induced obesity. Three-month intake of water infusions of dry cell biomass (100 mg/g body weight) against the background of a hypercaloric diet reduced weight gain and the proportion of fat mass in the obese animals. In addition, cell biomass preparation reduced the intracellular dehydration and balanced the amounts of intra- and extracellular fluids in the body as determined by bioimpedance spectroscopy. A significant decrease in the glucose and cholesterol levels in the blood was also observed as a result of cell biomass administration for all species. Hypocholesterolemic activity reduced in the line P. japonicus > D. deltoidea > T. terrestris/liraglutide > intact group > control group. By the sum of parameters tested, the cell culture of D. deltoidea was considered the most effective in mitigating diet-induced obesity, with positive effects sometimes exceeding those of the reference drug liraglutide. A safety assessment of D. deltoidea cell phytopreparation showed no toxic effect on the reproductive function of the animals and their offspring. These results support the potential application of the biotechnologically produced cell biomass of medicinal plant species as safe and effective natural remedies for the treatment of obesity and related complications, particularly for the long-term treatment and during pregnancy and lactation periods when conventional treatment is often contraindicated.

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

“…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].…”

Plants, Cells, Algae, and Cyanobacteria In Vitro and Cryobank Collections at the Institute of Plant Physiology, Russian Academy of Sciences—A Platform for Research and Production Center

“…Extensively used to study the regulation of steroidal glycoside biosynthesis in cell cultures [60]. Bioreactor-produced cell biomass was assessed for elemental composition [73], toxicology [82], and demonstrated positive effects in rats with induced type 2 diabetes mellitus and obesity [82,83].…”

“…Cell strain adapted for large-scale bioreactor cultivation [71] with a total content of ginsenosides (Rg 1 , malonyl-Rg 1 , Rb 1 , malonyl-Rb 1 , Rb 2 /Rb 3 , malonyl-Rb 2 /Rb 3 , Rd, malonyl-Rd, Rf, R 0 , chikusetsusaponin IVa) of 3.46% DW [85]. Bioreactor-produced cell biomass exhibited hypoglycemic and hypocholesterolemic activity in rats with diet-induced obesity [82].…”

“…Cell strain adapted for laboratory bioreactor cultivation with a total content of furostanol glycosides 0.1% DW [75]. Bioreactor-produced cell biomass positively affected rats with induced type 2 diabetes mellitus and obesity [82,83].…”

“…Phytopreparations based on cell cultures of Dioscorea deltoidea (strain DM-05-03), Panax japonicus (strain 62), and Tribulus terrestris (strain 8) exhibited a range of positive effects in rats with induced type 2 diabetes mellitus and obesity [ 82 , 83 ]. The toxicological evaluation of D. deltoidea cell biomass [ 82 ] and its elemental composition [ 73 ] were the first steps toward certification for commercial application.…”