Effect of Phytopreparations Based on Bioreactor-Grown Cell Biomass of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus on Carbohydrate and Lipid Metabolism in Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
- Panax japonicus (T. Nees) C.A. Mey., strain 62, in cell culture passport and some earlier publications referenced to as P. japonicus var. repens [33];
- Dioscorea deltoidea Wall. ex Griseb., super-producer of furostanol-type steroidal glycosides, strain DM-05–03 [26];
- Tribulus terrestris L., strain Tter8 [27].
2.2. Bioreactor Cultivation of Cell Suspensions, Biomass Preparation and Phytochemical Analysis
- Laboratory-scale bioreactors: 20 L (15 L working volume) glass bubble-type bioreactors custom-designed at the Department of cell biology and biotechnology, Institute of Plant Physiology, Moscow, Russia;
- Industrial-scale bioreactors: 630 L (550 L working volume) bubble-type bioreactors of 1T series (CUC “EBEE”, Yoshkar-Ola, Russia) with air supply through ring-type gas distributor ∅ 750 mm (Supplementary Materials Figure S1).
2.3. Evaluation of the Hypoglycemic Activity of Cell Biomass Preparations
2.3.1. Laboratory Animal Husbandry
2.3.2. Collection and Evaluation of Biological Material
2.3.3. Adrenaline Model of Hyperglycemia
2.3.4. Experimental Type 2 Diabetes Model (T2DM)
2.4. Statistical Data Processing
3. Results
3.1. Cell Culture Growth in Bioreactors and Their Biochemical Composition
3.2. Hypoglycemic Activity of Cell Culture Biomass in an Adrenaline Hyperglycemia Model
3.3. Activity of Cell Biomass Phytopreparations in Experimental STZ-Induced Model of Type 2 Diabetes Mellitus
3.4. Results of Histological Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Manipulation | Day of the Experiment 1 | |||||||
---|---|---|---|---|---|---|---|---|
0 2 | 1–42 | 43 | 44 (24 h STZ) | 45 (48 h STZ) | 46 (72 h STZ) | 47–53 1st Week of Treatment | 54–60 2nd Week of Treatment | |
High-fat diet | + | + | + | + | + | + | + | |
STZ administration 35 mg/kg | + | |||||||
Visual check for pathology development | + | + | + | + | + | |||
Drug administration | + | + | ||||||
Body weight measurement | + | + (21,42) | + (60) | + (60) | ||||
Blood-glucose-concentration measurement | + (42) | + | + | + | + (53) | + (60) | ||
Measuring the concentration of glucose in urine | + | + (42) | + | + | + (53) | + (60) | ||
Daily urine volume measurement | + | + (42) | + | + | + (53) | + (60) | ||
Blood cholesterol and triglyceride level measurement | + (42) | + | + (60) | |||||
Euthanasia | + (60) | |||||||
Histological examination | + (60) |
Cell Culture | Bioreactor Volume | Cell Viability, V (%) | Maximum Accumulation of Dry Weight, Mmax_dw (g/L) | Productivity, Pi_Max (g/(l⋅Day) | Specific Growth Rate, µdw, (Day−1) |
---|---|---|---|---|---|
D. deltoidea | 630 L | 83.5 ± 4.8 | 9.10 ± 2.76 | 0.37 ± 0.07 | 0.11 ± 0.03 |
T. terrestris | 20 L | 99.0 ± 1.0 | 14.0 ± 0.10 | 1.10 ± 0.20 | 0.3 ± 0.05 |
P. japonicus | 630 L | 84.2 ± 3.6 | 8.16 ± 1.84 | 0.31 ± 0.04 | 0.09 ± 0.02 |
Cell Culture | Bioreactor Volume | Bioactive Metabolites 1 | Total Content of Detected Bioactive Metabolites (% of Dry Cell Weight) |
---|---|---|---|
D. deltoidea | 630 L | Furostanol-type glycosides (deltoside, 25 (S)-protodioscin, protodioscin) [21,30] 2 | 4.62 ± 0.53 |
T. terrestris | 20 L | Furostanol-type steroidal glycosides [27,31] Caffeoylquinic acid, quinic acid (this study) | 0.10 ± 0.03 not determined |
P. japonicus | 630 L | Ginsenosides Rg1, malonyl-Rg1, Rb1, malonyl-Rb1, Rb2/Rb3, malonyl-Rb2/Rb3, Rd, malonyl-Rd, Rf, R0, chikusetsusaponin IVa) [28,29] | 3.46 ± 0.68 |
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Povydysh, M.N.; Titova, M.V.; Ivanov, I.M.; Klushin, A.G.; Kochkin, D.V.; Galishev, B.A.; Popova, E.V.; Ivkin, D.Y.; Luzhanin, V.G.; Krasnova, M.V.; et al. Effect of Phytopreparations Based on Bioreactor-Grown Cell Biomass of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus on Carbohydrate and Lipid Metabolism in Type 2 Diabetes Mellitus. Nutrients 2021, 13, 3811. https://doi.org/10.3390/nu13113811
Povydysh MN, Titova MV, Ivanov IM, Klushin AG, Kochkin DV, Galishev BA, Popova EV, Ivkin DY, Luzhanin VG, Krasnova MV, et al. Effect of Phytopreparations Based on Bioreactor-Grown Cell Biomass of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus on Carbohydrate and Lipid Metabolism in Type 2 Diabetes Mellitus. Nutrients. 2021; 13(11):3811. https://doi.org/10.3390/nu13113811
Chicago/Turabian StylePovydysh, Maria N., Maria V. Titova, Igor M. Ivanov, Andrey G. Klushin, Dmitry V. Kochkin, Boris A. Galishev, Elena V. Popova, Dmitry Yu. Ivkin, Vladimir G. Luzhanin, Marina V. Krasnova, and et al. 2021. "Effect of Phytopreparations Based on Bioreactor-Grown Cell Biomass of Dioscorea deltoidea, Tribulus terrestris and Panax japonicus on Carbohydrate and Lipid Metabolism in Type 2 Diabetes Mellitus" Nutrients 13, no. 11: 3811. https://doi.org/10.3390/nu13113811