• Food preservation and processing industry
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• v.7 no.1
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• pp.9-18
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• 2008

The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.341-354
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• 2021

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1079-1087
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• 2018

Purpose: Obstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease (CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however, underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS can lead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the intervention effects of antioxidant tempol. Materials and Methods: Male Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia (IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed in OS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh blood were harvested for analysis of endothelial markers and apoptosis. Results: The levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelial cells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group, and were lower in OST group than in OS and OSN groups (all p<0.001). Conclusion: Synergistic effects of IH with cigarette smoke-induced emphysema produce a greater inflammatory status and endothelial apoptosis. OS-related inflammation and endothelial cell apoptosis may play important roles in promoting cardiovascular dysfunction, and antioxidant tempol could achieve a partial protective effect.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.572-584
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• 2022

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

• Journal of Convergence Korean Medicine
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• v.5 no.1
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• pp.45-54
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• 2023

Objectives : Alcohol-induced liver disease advances as to reactive oxygen species (ROS) and cellular lipid peroxidation increase. We examined the hepatoprotective effects of Zingiber officinale Roscoe rhizome extract (ZR), Pueraria lobata Ohwi flower extracts (PF), and a newly developed herbal juice (HJ), which was a combination of ZR and PF extracts, against ethanol-induced hepatotoxicity. Methods: The study utilized the human hepatoma cell line HepG2 cells to validate the hepatoprotective effect of HJ (50~200 ㎍/mL) against ethanol (EtOH, 700 mM)-induced liver damage. Results: HJ effectively reduced the protein expression of sterol regulatory element-binding transcription factor 1, adiponectin, and AMP-activated protein kinase in EtOH-induced HepG2 cells. The levels of ROS, total cholesterol, and triglycerides, which are the result of various synthesis and lipogenesis processes induced by EtOH in the liver, were reduced by HJ. Furthermore, the activities of alcohol dehydrogenase and aldehyde dehydrogenase, enzymes linked to alcohol degradation, were more effectively downregulated by HJ treatment compared to treatment with ZR and PF alone, all without causing cytotoxic effects. Conclusions: HJ protects the liver by inhibiting EtOH-induced lipogenesis, lowering ROS generation, and improving alcohol degradation, which is more effective than ZR and PF alone. Further, in vivo experiments can offer additional evidence regarding the effectiveness, safety, and underlying mechanism of action of HJ.

• Molecules and Cells
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• v.46 no.10
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• pp.627-636
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• 2023

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.211-219
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• 2024

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 10⁹ particles/mL), and followed by UVB irradiation or H₂O₂ exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

• Journal of Applied Biological Chemistry
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• v.60 no.2
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• pp.141-147
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• 2017

Radical scavenging effect and protective activity against oxidative stress of Acer okamotoanum were investigated. A. okamotoanum was extracted with methanol (MeOH) and then fractionated with n-BuOH, ethyl acetate (EtOAc), methylene chloride and n-hexane fractions. The MeOH extract and fractions showed strong 1,1-diphenyl-2-picrylhydrazyl and superoxide radical scavenging activity. Among the MeOH extract and fractions, the EtOAc fraction showed the strongest radical scavenging activity. In addition, total phenolic and flavonoid contents of EtOAc fraction was higher than other extract and fractions. Furthermore, we investigated the neuroprotective effect of the MeOH extract and fractions from A. okamotoanum against oxidative stress under cellular system using C6 glial cell. The C6 glial cells showed a decrease in cell viability and high production of reactive oxygen species (ROS) by the treatment of amyloid $beta_{25-35}$ ($A{\beta}_{25-35}$). However, with the treatment of the MeOH extract and fractions, it significantly increased the cell viability and inhibited the overproduction of ROS by $A{\beta}_{25-35}$. In particular, the EtOAc fraction led to significantly increase the cell viability and decrease the generation of ROS against oxidative stress by $A{\beta}_{25-35}$. The current study indicated that A. okamotoanum demonstrated antioxidative and neuroprotective effects. In particular, the EtOAc fraction which attributed a strong protective activity against oxidative stress.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.41-48
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• 2002

Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.1
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• pp.11-20
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• 2014

In this work, the antioxidative effects and active component analysis of Gnaphalium affine D. DON. (G. affine) extracts were investigated. All experiments were performed with 70% ethanol extract, ethyl acetate fraction and aglycone fraction of the G. affine extract. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity ($FSC_{50}$) of ethyl acetate fraction ($6.15{\mu}g/mL$) of the G. affine was higher than that of (+)-${\alpha}$-tocopherol ($8.89{\mu}g/mL$), which is known as a reference control. Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of the 70% ethanol extract ($1.60{\mu}g/mL$), ethyl acetate fraction ($0.075{\mu}g/mL$) and aglycone fraction ($2.28{\mu}g/mL$) of extract of G. affine on ROS generated in $Fe^{3+}$-EDTA/$H_2O_2$ system using the luminol-dependent chemiluminescence assay were much higher than that of L-ascorbic acid ($6.88{\mu}g/mL$). The cellular protective effects of 70% ethanol extract (${\tau}_{50}$ = 52.0 min) and aglycone fraction of the extract (${\tau}_{50}$ = 60.6 min) on the $^1O_2$-induced cellular damage of human erythrocytes were exhibited the higher protective effect than (+)-${\alpha}$-tocopherol (${\tau}_{50}$ = 38.0 min), known as a lipophilic antioxidant. TLC and HPLC were used to analyse active components in the aglycone fraction of the extract. Results showed that luteolin and apigenin were main components. These results suggest that the G. affine extract can be applied to an effective antioxidant in scavenging ROS including radicals.