Efficient Thermal Deglycosylation of Ginsenoside Rd and Its Contribution to the Improved Anticancer Activity of Ginseng

Abstract

The root of ginseng is a famous functional food and a herbal medicine. Research into the development of a method for increasing the pharmaceutical effect of ginseng by conversion of ginsenosides, the major active components of ginseng, by high-temperature and high-pressure thermal processing has been conducted. However, changes in the structures of each ginsenoside by heat processing and their contributions to anticancer activity have not yet been fully elucidated. Here, we investigated whether anticancer activity of ginsenosides, such as Rb1, Rb2, Rc, Rd, and Re, was associated with changes in the structures of each ginsenoside by heat processing in human stomach cancer AGS cells. Upon heat processing at 120 °C, most peaks of ginsenosides Rb1, Rb2, Rc, and Rd disappeared and the contents of less-polar ginsenosides 20(S,R)-Rg3, Rk1, and Rg5 were newly detected. From the quantitative analysis of ginsenosides, the generated amounts of less-polar ginsenosides were the highest after heat processing of ginsenoside Rd. After heat processing, the diol-type ginsenosides Rb1, Rb2, Rc, and Rd gained significant antiproliferative activity. In particular, ginsenoside Rd induced the strongest cell death among the diol-type ginsenosides, whereas the triol-type gisenoside Re showed weak antiproliferative activity. Ginsenoside Rd-induced cell death was associated with caspase-dependent apoptosis. Taken together, these results demonstrate that deglycosylation of Rd contributes to improved anticancer activity of ginseng and provide new insight on the mechanism of increased anticancer effects of ginsenosides upon heat processing.

Protective Effects of Processed Ginseng and Its Active Ginsenosides on Cisplatin-Induced Nephrotoxicity: In Vitro and in Vivo Studies

“…11,18,19 Ginsenoside Rg3 is converted to Rg5 and Rk1 by further dehydration at the carbon-20 position by high pressure and temperature. 13,19 Using LLC-PK1 renal epithelial cells as the in vitro model, we compared the protective activities of WG, MG, MG−MeOH, MG−H 2 O, ginsenoside Rg3 epimers, and ginsenoside Rg5/Rk1 against cisplatin-induced oxidative renal damage. The ginsenoside stereoisomers were used as mixtures because of the difficulty in preparing a single ingredient with high purity.…”

“…Ginsenosides were identified and quantified using a previously reported method. 13 An analytical reversedphase HPLC system comprised of a solvent degasser (Agilent, G1322A), binary pump (Agilent, G1312C), and model 380 evaporative light scattering detector (ELSD, Agilent) was used in the analysis. The standard solutions containing 1−100 μg of each ginsenoside were injected onto the HPLC column, with all calibration curves showing good linearity (R 2 > 0.995).…”

“…Ginsenosides are generally divided into protopanaxadiol and protopanaxatriol groups based on the chemical structures of aglycone moieties ( Figure 1). 11,13 In our recent research on the protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, and Rd, the sugar moieties at carbon-20 were removed by thermal processing and the aglycones were changed into Rg3, Rg5, and Rk1 ( Figure 1). 13 Microwave thermal processing has been used to process a wide range of products, including foods.…”

Semi-synthesis of Twelve Known 20<i>Z</i>/<i>E</i> Pseudo-Ginsenosides and Their Comparative Study of Antioxidative Activity in Free Radical Induced Hemolysis of Rabbit Erythrocytes

“…Pharmacological studies on ginsenosides have reported neuroprotective, anti-HIV, antioxidant and anticancer effects. [23][24][25] The major active components ginsenosides that was used in traditional Chinese medicine has been proved to be antioxidants against AAPH-induced hemolysis of erythrocytes. 26) In the previous study, many dammarane-type derivatives have been prepared and investigated for their activities.…”

Identification and Characterization of a Ginsenoside-Transforming β-Glucosidase from Pseudonocardia sp. Gsoil 1536 and Its Application for Enhanced Production of Minor Ginsenoside Rg2(S)

“…As secondary metabolite compounds, the minor ginsenosides have some chemical reactivity that the major ginsenosides do not. Furthermore, there is emerging evidence that the minor ginsenosides have more important pharmaceutical effects, such as anti-cancer, anti-diabetic, anti-oxidative, and anti-aging effects, than the glycosylated major ginsenosides [10], [11], [13], [14], [15].…”