Active absorption of ginsenoside Rg1 <i>in vitro</i> and <i>in vivo</i>: the role of sodium-dependent glucose co-transporter 1

Xiong, Jing; Sun, Minjie; Guo, Zhixiong; Huang, Luosheng; Wang, Shujing; Meng, Boyu; Ping, Qineng

doi:10.1211/jpp.61.03.0014

Cited by 8 publications

(14 citation statements)

References 29 publications

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“… 28 − 30 Caco-2 cells are known to express active transporters, including sugar transporters, such as SGLT1, GLUT2, and GLUT5. 10 A study by Liu et al also reported that a sugar transporter, SGLT1, is responsible for the transport of glycosides in Caco-2 cells. 31 Analyzing our permeability assay data with the literature reports in mind, it can be interpreted that the glycosylated flavonoids assessed here may be actively transported, possibly by sugar transporters across Caco-2 monolayers.…”

Section: Resultsmentioning

confidence: 98%

“…These saponins are actively transported by suitable transport proteins, such as sugar transporters, or can be effluxed across the monolayers by efflux pumps such as P-gp and MRP-2. 10 , 32 − 36 We know that Caco-2 cells express active transporters including sugar transporters such as SGLT1 (responsible for the transport of glycosides), 31 GLUT2 and GLUT5. 10 Analysis of our permeability assay data in light of these literature reports suggests that the glycosylated saponins assessed here may be actively transported by sugar transporters across Caco-2 monolayers.…”

Section: Resultsmentioning

confidence: 99%

“… 10 , 32 − 36 We know that Caco-2 cells express active transporters including sugar transporters such as SGLT1 (responsible for the transport of glycosides), 31 GLUT2 and GLUT5. 10 Analysis of our permeability assay data in light of these literature reports suggests that the glycosylated saponins assessed here may be actively transported by sugar transporters across Caco-2 monolayers. The low permeability of saponins 13 and 15 may be attributed to the fact that these saponins are effluxed across Caco-2 monolayers by suitable efflux pumps such as P-gp and MRP-2.…”

Section: Resultsmentioning

confidence: 99%

“… 6 − 8 Caco-2 cells provide an excellent physical and biochemical mimic of the human intestinal epithelial membrane. 5 When the cells are cultured following specific protocols 9 and they reach expected differentiation and confluency, they express all the major transport proteins present in the human small intestine such as active transporters including sugar transporters, e.g., SGLT1, GLUT2, and GLUT5, 10 thus allowing passive diffusion as well as active and passive transport to be investigated. 11 They also express efflux proteins such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP-2).…”

Section: Introductionmentioning

confidence: 99%

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Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb

Ahmed

Leach²,

Wohlmuth

et al. 2020

ACS Omega

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Gynostemma pentaphyllum (the immortal herb) has been an important component of Chinese Traditional Medicine for millennia. Recent clinical studies have revealed that the plant exhibits numerous beneficial biological activities, making it of interest to the pharmaceutical industry. An extract of the herb contains over 200 individual secondary metabolites including flavonol glycosides and dammarane saponins. To focus attention on the compounds most likely to be responsible for the biological activities, this study predicts the potential oral bioavailability of nine dammarane saponins and five flavonol glycosides from G. pentaphyllum using the Caco-2 cell monolayer permeability model. Two flavonoids, 8 and 9 , and four saponins, 10 , 11 , 12 , and 14 , exhibited high permeability across the monolayers. The results indicated that a higher degree of glycosylation-facilitated permeability, suggestive of active transport. This study demonstrates the utility of the Caco-2 permeability assay as a method of identifying possible bioavailable compounds from medicinal herbal extracts.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb

Ahmed

Leach²,

Wohlmuth

et al. 2020

ACS Omega

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“…For example, both in vitro and in vivo studies have shown that the transport of ginsenoside Rb1 across the blood-brain barrier was mediated by glucose transporter 1 (GLUT1) 28. Similarly, a previous study revealed that ginsenoside Rg1 was actively transported via sodium-coupled glucose co-transporter 1 (SGLT1) into the intestine 29. Thus, ginsenoside has the potential to work as an active targeting ligand to facilitate the accumulation of drug-loading liposomes at the tumor site via interaction with the GLUT of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Novel ginsenoside-based multifunctional liposomal delivery system for combination therapy of gastric cancer

et al. 2019

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The clinical treatment of gastric cancer (GC) is hampered by the development of anticancer drug resistance and the unfavorable pharmacokinetics, off-target toxicity, and inadequate intratumoral accumulation of the current chemotherapy treatments. Ginsenosides combined with paclitaxel (PTX) have been shown to exert synergistic inhibition of human GC cell proliferation. In the present study, we developed a novel multifunctional liposome system, in which ginsenosides functioned as the chemotherapy adjuvant and membrane stabilizer. These had long blood circulation times and active targeting abilities, thus creating multifunctionality of the liposomes and facilitating drug administration to the GC cells. Methods: Three ginsenosides with different structures were used to formulate the unique nanocarrier, which was prepared using the thin-film hydration method. The stability of the ginsenoside liposomes was determined by particle size analysis using dynamic light scattering. The long circulation time of ginsenoside liposomes was compared with that of conventional liposome and polyethylene glycosylated liposomes in vivo . The active targeting effect of ginsenoside liposomes was examined with a GC xenograft model using an in vivo imaging system. To examine the antitumor activity of ginsenoside liposomes against GC, MTT, cell cycle, and apoptosis assays were performed on BGC-823 cells in vitro and PTX-loaded ginsenoside liposomes were prepared to evaluate the therapeutic efficacy on GC in vivo . Results: The ginsenosides stabilized the liposomes in a manner similar to cholesterol. We confirmed the successful delivery of the bioactive combination drugs and internalization into GC cells via analysis of the glucose-related transporter recognition and longer blood circulation time. PTX was encapsulated in different liposomal formulations for use as a combination therapy, in which ginsenosides were found to exert their inherent anticancer activity, as well as act synergistically with PTX. The combination therapy using these targeted liposomes significantly suppressed GC tumor growth and outperformed most reported PTX formulations, including Lipusu ® and Abraxane ® . Conclusion: We established novel ginsenoside-based liposomes as a tumor-targeting therapy, in which ginsenoside functioned not only as a chemotherapy adjuvant, but also as a functional membrane material. Ginsenoside-based liposomes offer a novel platform for anticancer drug delivery and may lead to a new era of nanocarrier treatments for cancer.

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Increased effects of ginsenosides on the expression of cholesterol 7α-hydroxylase but not the bile salt export pump are involved in cholesterol metabolism

et al. 2012

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An extract from red ginseng [steamed and dried roots of Panax ginseng C.A. Meyer (RGE)] has been shown to have various actions on physiological functions. The mechanisms by which RGE promotes cholesterol metabolism in the liver are unclear, but RGE decreases the plasma levels of cholesterol. We investigated whether RGE affected the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed the upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with RGE. Treatment with RGE exhibited decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol compared with hypercholesterolemia without RGE. In-vitro studies also showed the upregulation of CYP7A1 mRNA and protein levels by the addition of RGE to rat primary hepatocytes. The mRNA levels of BSEP exhibited few changes. The sustained levels of the liver X receptor (LXR) in vivo and the increased levels of LXR in vitro on RGE treatment could be involved in the upregulation of CYP7A1. To clarify the effects of 11 ginsenosides including RGE on the mRNA levels of CYP7A1 and BSEP, we performed in-vitro experiments using rat primary hepatocytes. The ginsenosides Ro, Rg3, Re, Rg1, and Rg2 exhibited increased mRNA levels of CYP7A1. These results suggest that several ginsenosides including RGE promoted cholesterol metabolism due to upregulation of CYP7A1.

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Active absorption of ginsenoside Rg1 in vitro and in vivo: the role of sodium-dependent glucose co-transporter 1

Abstract: The data suggested that adrenaline enhanced the absorption of Rg1 by regulating sodium-dependent glucose co-transporter 1.

Cited by 8 publications

References 29 publications

Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb

Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb

Novel ginsenoside-based multifunctional liposomal delivery system for combination therapy of gastric cancer

Increased effects of ginsenosides on the expression of cholesterol 7α-hydroxylase but not the bile salt export pump are involved in cholesterol metabolism

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