• Journal of Ginseng Research
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• v.44 no.6
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• pp.808-814
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• 2020

Background: Korean Red Ginseng extract (RGE) has been reported to act as an inflammasome modulator. Ginsenosides, saponin molecules of RGE, selectively inhibit activation of NLRP3 and AIM2 inflammasomes, while non-saponin molecules of RGE upregulate inflammasome components associated with the initiation of NLRP3 inflammasome activation. In this study, we investigated the effect of non-saponin components of RGE on AIM2 inflammasome activation. Methods: The role of non-saponins of RGE on AIM2 inflammasomes was tested in mouse bone marrow-derived macrophages, a human monocyte-like cell line, and a mouse animal model. Cells or mice were transfected with dsDNA or inoculated with Listeria monocytogenes to activate AIM2 inflammasomes. Several indices of inflammasome activation were examined via immunoblot or ELISA analysis. Results: The non-saponin fraction and saponin-eliminating fraction (SEF) of RGE selectively attenuated the activation of AIM2 inflammasomes, but not that of NLRP3 or NLRC4 inflammasomes. Fructose-arginine, an amino-sugar, was shown to be effective against AIM2 inflammasome activation. Conclusion: Non-saponins of RGE, such as fructose-arginine, might be effective in regulating infectious and autoimmune diseases resulting from AIM2 inflammasome activation.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.104-114
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• 2022

Background: Abnormalities of myelin, which increases the efficiency of action potential conduction, are found in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy against some of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, we examined the effects of KRG-derived components on development and protection of OL-lineage cells. Methods: Primary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. The protective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adult male mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. Results: The non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Both processes were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, the saponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponin significantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested, Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelin formation in adult mouse brain. Conclusion: All KRG components prevented OPC deaths under oxidative stress. While non-saponin promoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size and significantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 for myelin-related disorders.

• Journal of Ginseng Research
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• v.21 no.1
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• pp.53-60
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• 1997

The changes in aldehyde dehydrogenase(ALDH, E.C. 1.2.1.3.) activity in neurons and astrocytes isolated from rat brains were investigated after administration of ethanol and Korean red ginseng(Panax ginseng C.A. Meyer) saponln. The cerebral ALDH activity with acetaldehyde and Propionaldehyde was higher in the white matter than in the gray matter. However, using indole-3-a-cetaldehyde and 3,4-dihydroxyphenylacetaldehyde as substrates, there was no significant difference in activity between two regions in cerebrum. In ethanol treated group, ALDH activity with all the substrates in the gray and white matter was lower than in normal group. In ethanol-saponin treated group, the enzyme activity in the white matter remarkably Increased. The ALDH activity in neurons isolated from cerebral cortex in ethanol-treated group was lower than in normal group. In ethanol-saponin treated group, neuronal ALDH activity with propionaldehyde was significantly recovered but not with Indole-3-acetaldehyde. In astrocytes, although the ALDH activity with propionaldehyde in the ethanol-treated group was not changed as compared with normal group, considerable increase in activity was found in ethanol-saponin treated group. These results suggest that Korean red ginseng saponin may protect the neuronal functions from the toxic effects of acetaldehyde derived from ethanol by stimulation of ALDH activity in astrocytes surrounding nerve cells.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.437-444
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• 2016

Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.688-696
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• 2018

This study aimed to investigate the effects of red ginseng-derived saponin fraction (SF) on lipid accumulation, reactive oxygen species (ROS) production, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling during adipocyte differentiation. SF effectively inhibited lipid accumulation, with the downregulation of adipogenic factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha ($C/EBP{\alpha}$). A high dose of SF decreased the protein levels of $PPAR{\gamma}$ and $C/EBP{\alpha}$ by over 90% compared to the control. SF-mediated downregulation of adipogenic factors was due to the regulation of early adipogenic factors including $C/EBP{\beta}$ and $Kr{\ddot{u}}ppel$-like Factor 2 (KLF2). In addition, SF ($200{\mu}g/mg$) decreased intracellular ROS generation by 40% during adipocyte differentiation. However, the SF significantly upregulated Nrf2 and its target proteins, hemoxygenase-1 (HO-1) and NADPH dehydrogenase quinone 1 (NQO1). Furthermore, SF ($200{\mu}g/mg$) promoted the nuclear translocation of Nrf2. The SF-mediated reduction of lipid accumulation was associated with the regulation of the Nrf2/Keap1 pathway.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.291-299
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• 2019

Background: Ginsenosides of Korean Red Ginseng extracts (RGE) and its saponin components suppress secretion of inflammasome-mediating cytokines, whereas the nonsaponin fraction (NS) of RGE oppositely stimulates cytokine secretion. Although direct exposure of NS to macrophages in mice induces cytokine production, oral administration of NS has not been studied in inflammasome-related disease in animal models. Methods: Mice were fed RGE or NS for 7 days and then developed peritonitis. Peritoneal cytokines were measured, and peritoneal exudate cells (PECs) were collected to assay expression levels of a set of toll-like receptors (TLRs) and cytokines in response to NS ingestion. In addition, the role of intestinal bacteria in NS-fed mice was assessed. The effect of preexposure to NS in bone marrow-derived macrophages (BMDMs) on cytokine production was further confirmed. Results: NS ingestion attenuated secretion of peritoneal cytokines resulting from peritonitis. In addition, the isolated PECs from NS-fed mice presented lower TLR transcription levels than PECs from control diet-fed mice. BMDMs treated with NS showed downregulation of TLR4 mRNA and protein expression, which was mediated by the $TLR4-MyD88-NF{\kappa}B$ signal pathway. BMDMs pretreated with NS produced less cytokines in response to TLR4 ligands. Conclusion: NS administration directly inhibits TLR4 expression in inflammatory cells such as macrophages, thereby reducing secretion of cytokines during peritonitis.

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.70-80
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• 2019

The aim of this study was to investigate the effects of red ginseng-derived non-saponin fraction (NSF) on inflammatory responses and monocyte-to-macrophage differentiation in RAW264.7 and THP-1. NSF effectively inhibited inflammatory responses by downregulating nitric oxide (NO) production and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). NSF ($2000{\mu}g/mL$) decreased the levels of NO, iNOS, and COX-2 by 33, 83, and 64%, respectively. NSF inhibited the differentiation of monocyte-to-macrophage by decreasing cell adherence along with downregulation of the cluster of differentiation molecule $11{\beta}$ ($CD11{\beta}$) and CD36. In addition, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin 6, and monocyte chemoattractant protein 1 (MCP-1), were significantly reduced with NSF treatment. The NSF-mediated inhibition of inflammatory responses was due to the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). NSF effectively suppressed the translocation of $NF-{\kappa}B$ into the nucleus, while nuclear Nrf2 and its target protein, heme oxygenase-1, levels were significantly increased.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.593-603
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• 2023

Background: Korean Red Ginseng is a major source of bioactive substances such as ginsenosides. Efficacy of red ginseng extract (RGE), which contains not only saponins but also various non-saponins, has long been studied. In the water-soluble component-rich fraction of RGE (WS), a byproduct generated in the process of extracting saponins from the RGE, we identified previously unidentified molecules and confirmed their efficacy. Methods: The RGE was prepared and used to produce WS, whose components were isolated sequentially according to their water affinity. The new compounds from WS were fractionized and structurally analyzed using nuclear magnetic resonance spectroscopy. Physiological applicability was evaluated by verifying the antioxidant and anti-inflammatory efficacies of these compounds in vitro. Results: High-performance liquid chromatography confirmed that the obtained WS comprised 11 phenolic acid and flavonoid substances. Among four major compounds from fractions 1-4 (F1-4) of WS, two compounds from F3 and F4 were newly identified in red ginseng. The analysis results show that these compound molecules are member of the maltol-structure-based glucopyranose series, and F1 and F4 are particularly effective for decreasing oxidative stress levels and inhibiting nitric oxide secretion, interleukin (IL)-1β and IL-6, and tumor necrosis factor-α. Conclusion: Our findings suggest that a few newly identified maltol derivatives, such as red ginseng-derived non-saponin in the WS, exhibit antioxidant and anti-inflammatory effects, making them viable candidates for application to pharmaceutical, cosmetic, and functional food materials.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.386-391
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• 2017

Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.