• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.182-189
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• 1998

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

• Korean Journal of Medicinal Crop Science
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• v.26 no.2
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• pp.148-156
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• 2018

Background: Hot steaming is known to be effective in improving the biological activities of plant extracts by breaking down useful compounds to low molecular weight ones. Methods and Results: This study aimed to develop an optimal extraction and steam processing method for enhancing the low molecular ginsenoside contents of the adventitious roots culture of wild mountain ginseng. The total ginsenoside was optimally extracted when 70% EtOH was used at $50^{\circ}C$, whereas low molecule ginsenoside such as Rg2, Rh1, Rh4 and Rk1 could be extracted using 70% EtOH at $70^{\circ}C$. The adventitious roots culture of wild mountain ginseng is known to contain four major ginsenosides, i.e., Rb2, Rb1, Rg1 and Rd, however new ginsenosides Rg6, Rh4, Rg3, Rk1 and Rg5 were new abundantly obtaind after steam processing method was applied. The contents of total ginsenosides were the highest when thermal steam processing was conducted at $120^{\circ}C$ for 120 min. Unlike ginsenosides such as Rg1, Re, Rb1, Rc, Rb2, and Rh1, which decreased after steam processing, Rg3, Rk1, and Rg5 increased after thermal processing. Steam processing significanltly reduced the content of Rb1, increased that of Rg6 by about ten times than that in the adventitious roots culture of wild mountain ginseng. Conclusions: Our study showed that the optimal extraction and steam processing method increased the content of total ginsenosides and allowed the extraction of minor ginsenosides from major ones.

• 한국약용작물학회:학술대회논문집
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• 2011.09a
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.80-86
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• 2013

Korean red ginseng has been shown to possess a variety of biological activities. However, little is known about antiviral activity of ginsenosides of Korean red ginseng. Here, we investigated the protective effect by oral administration of various ginsenosides on the lethal infection of haemagglutinating virus of Japan (HVJ) in mice. In a lethal infection model in which almost all mice infected with HVJ died within 15 days, the mice were administered orally (per os) with 1 mg/mouse of dammarane-type (ginsenoside-Rb1, -Rb2, -Rd, -Re, and -Rg2) or oleanolic acid-type (ginsenoside-Ro) ginsenosides 3, 2, and 1 d before virus infection. Ginsenoside-Rb2 showed the highest protective activity, although other dammarane-type and oleanolic acid-type ginsenosides also induced a significant protection against HVJ. However, neither the consecutive administration with a lower dosage (300 ${\mu}g$/mouse) nor the single administration of ginsenoside-Rb2 (1 mg/mouse) was active. In comparison of the protective activity between ginsenoside-Rb2 and its two hydrolytic products [20(S)- and 20(R)-ginsenoside-Rg3], 20(S)-ginsenoside-Rg3, but not 20(R)-ginsenoside-Rg3, elicited a partial protection against HVJ. The protective effect of ginsenoside-Rb2 and 20(S)-ginsenoside-Rg3 on HVJ infection was confirmed by the reduction of virus titers in the lungs of HVJ-infected mice. These results suggest that ginsenoside-Rb2 is the most effective among ginsenosides from red ginseng to prevent the lethal infection of HVJ, so that this ginsenoside is a promising candidate as a mucosal immunoadjuvant to enhance antiviral activity.

• Preventive Nutrition and Food Science
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• v.14 no.3
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• pp.201-207
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• 2009

In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

• Journal of Ginseng Research
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• v.42 no.4
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• pp.412-418
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• 2018

Background: Ginsenoside Rg3(S) and compound K (C-K) are pharmacologically active components of ginseng that promote human health and improve quality of life. The aim of this study was to produce Rg3(S) and C-K from ginseng extract using recombinant Lactococcus lactis. Methods: L. lactis subsp. cremoris NZ9000 (L. lactis NZ9000), which harbors ${\beta}$-glucosidase genes (BglPm and BglBX10) from Paenibacillus mucilaginosus and Flavobacterium johnsoniae, respectively, was reacted with ginseng extract (protopanaxadiol-type ginsenoside mixture). Results: Crude enzyme activity of BglBX10 values comprised 0.001 unit/mL and 0.003 unit/mL in uninduced and induced preparations, respectively. When whole cells of L. lactis harboring pNZBglBX10 were treated with ginseng extract, after permeabilization of cells by xylene, Rb1 and Rd were converted into Rg3(S) with a conversion yield of 61%. C-K was also produced by sequential reactions of the permeabilized cells harboring each pNZBgl and pNZBglBX10, resulting in a 70% maximum conversion yield. Conclusion: This study demonstrates that the lactic acid bacteria having specific ${\beta}$-glucosidase activity can be used to enhance the health benefits of Panax ginseng in either fermented foods or bioconversion processes.

• The Journal of the Convergence on Culture Technology
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• v.4 no.4
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• pp.317-324
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• 2018

This study was carried out to investigate the optimum conditions for extraction of ginsenoside active ingredients from red ginseng residue and mugwort bark extract produced by manufacturing alcoholic and water extract from red ginseng residue and mugwort bark extract. Extraction efficacy of ginsenoside active ingredients from extracted red ginseng residue and mugwort bark extract was higher than that before extracting. We suggests that red ginseng residue and mugwort bark extract produced by manufacturing alcholic and water extract of red ginseng and mugwort has higher potencies in the utilization of waste materials.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.171-180
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• 2024

Background: Epimers of ginsenoside Rg3 (Rg3) have a low bioavailability and are prone to deglycosylation, which produces epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The aim of this study was to compare the efficacy and potency of these molecules as anti-cancer agents. Methods: Crystal violet staining was used to study the anti-proliferatory action of the molecules on a human epithelial breast cancer cell line, MDA-MB-231, and human umbilical vein endothelial cells (HUVEC) and compare their potency. Cell death and cell cycle were studied using flow cytometry and mode of cell death was studied using live cell imaging. Anti-angiogenic effects of the drug were studied using loop formation assay. Molecular docking showed the interaction of these molecules with vascular endothelial growth factor receptor-2 (VEGFR2) and aquaporin (AQP) water channels. VEGF bioassay was used to study the interaction of Rh2 with VEGFR2, in vitro. Results: HUVEC was the more sensitive cell line to the anti-proliferative effects of S-Rh2, S-PPD and R-PPD. The molecules induced necroptosis/necrosis in MDA-MB-231 and apoptosis in HUVEC. S-Rh2 was the most potent inhibitor of loop formation. In silico molecular docking predicted a good binding score between Rh2 or PPD and the ATP-binding pocket of VEGFR2. VEGF bioassay showed that Rh2 was an allosteric modulator of VEGFR2. In addition, SRh2 and PPD had good binding scores with AQP1 and AQP5, both of which play roles in cell migration and proliferation. Conclusion: The combination of these molecules might be responsible for the anti-cancer effects observed by Rg3.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.458-468
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• 2023

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

• Preventive Nutrition and Food Science
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• v.14 no.2
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• pp.156-161
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• 2009

Effects of extrusion conditions (barrel temperature and moisture content) and fermentation time on the antioxidant properties of root hair of tissue cultured raw mountain ginseng (MG) were investigated. The barrel temperature/ moisture combinations were: $110^{\circ}C$/25% (MG1), $140^{\circ}C$/25% (MG2), $110^{\circ}C$/35% (MG3) and $140^{\circ}C$/35% (MG4). Red ginseng (RG) was also investigated. The contents of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and polyphenolic increased after fermentation in RG and even more in MG, while extruded ginseng samples exhibited little change. The increases noted with MG and RG occurred during the first 4 days of fermentation. DPPH radical scavenging activity decreased after extrusion and was significantly higher in MG (20.93%) than RG (1.63%) on the first day of fermentation. DPPH radical scavenging activity in the barrel temperature/moisture combinations were 19.01% (MG1), 14.45% (MG2), 20.37% (MG3) and 15.78% (MG4). The content of polyphenolic compounds in ginseng samples displayed a similar trend. Acidic polysaccharide in RG and MG1${\sim}$MG4 were higher than MG, but decreased during fermentation. Crude saponin in RG and MG1${\sim}$MG4 decreased after 15 days of fermentation, while increasing in MG.