• Journal of Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• Molecules and Cells
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• v.37 no.11
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• pp.833-840
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• 2014

Cullin4-RING ubiquitin ligase (CRL4) is a family of multi-subunit E3 ligases. To investigate the possible involvement of CRL4 in heat stress response, we screened T-DNA insertion mutants of putative CRL4 substrate receptors that exhibited altered patterns in response to heat stress. One of the mutants exhibited heat stress tolerance and was named heat stress tolerant DWD1 (htd1). Introduction of HTD1 gene into htd1-1 led to recovery of heat sensitivity to the wild type level, confirming that the decrease of HTD1 transcripts resulted in heat tolerance. Therefore, HTD1 plays a negative role in thermotolerance in Arabidopsis. Additionally, HTD1 directly interacted with DDB1a in yeast two-hybrid assays and associated with DDB1b in vivo, supporting that it could be a part of a CRL4 complex. Various heat-inducible genes such as HSP14.7, HSP21, At2g03020 and WRKY28 were hyper-induced in htd1-1, indicating that HTD1 could function as a negative regulator for the expression of such genes and that these genes might contribute to thermotolerance of htd1-1, at least in part. HTD1 was associated with HSP90-1, a crucial regulator of thermotolerance, in vivo, even though the decrease of HTD1 did not affect the accumulation pattern of HSP90-1 in Arabidopsis. These findings indicate that a negative role of HTD1 in thermotolerance might be achieved through its association with HSP90-1, possibly by disturbing the action of HSP90-1, not by the degradation of HSP90-1. This study will serve as an important step toward understanding of the functional connection between CRL4-mediated processes and plant heat stress signaling.

• Nutrition Research and Practice
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• v.7 no.4
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• pp.273-280
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• 2013

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked $9{\times}$) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-${\gamma}$, and tumor necrosis factor (TNF)-${\alpha}$. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-${\alpha}$, and IL-$1{\beta}$, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent $CCl_4$-induced hepatic damage in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3035-3042
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• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.543-551
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• 2023

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

• Journal of Microbiology and Biotechnology
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• v.9 no.6
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• pp.826-831
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• 1999

${\beta}-Glucan$, one of the major cell wall components of Saccharomyces cerevisiae, is known to enhance the immune function, especially by activating macrophages. Accordingly, in an effort to develop a safe and efficient immune stimulatory agent, we prepared crude ${\beta}-glucan$ (glucan-p1) and partially purified ${\beta}-glucan$ that was free of mannoproteins (glucan-p2), and evaluated their effect on both the macrophage function and resistance to E. coli-induced peritonitis. To investigate the function of the macrophages, phagocytosis, $TNF-{\alpha}$ secretion, oxygen burst, and the expression of cytokine genes such as $IFN-{\gamma}$ and IL-12 were analyzed. Glucan-p2 markedly stimulated the macrophages with all these parameters. Glucan-p1, however, did not stimulate phagocytosis, yet it induced $TNF-{\alpha}$ secretion, oxygen burst, and the expression of $IFN-{\gamma}$ and IL-12, although less efficiently than glucan-p2. Finally, to test the in vivo protective effect of {\beta}-glucan against infection, the survival of mice from E. coli-induced peritonitis was investigated. After 24 h of the peritoneal challenge of E. coli, all of the mice treated with glucan-p2 survived whereas none survived in the control group. Glucan-p1 showed only a marginal effect in protecting the mice. These results suggest that mannoprotein-free gluean-p2, but not gluean-p1, can serve as an effective immune-stimulating agent.

• Korean Journal of Environmental Biology
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• v.29 no.1
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• pp.61-67
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• 2011

N-acetyl-L-cysteine (NAC) having a thiol, a precursor for glutathione (GSH), is known as one of the antioxidants. NAC used as a radioprotector against ionizing radiation (IR)-induced injury and damage. The aim of this study was to evaluate the radioprotective effects of NAC against IR-induced cell damage in Saccharomyces cerevisiae and the antioxidative effect of NAC on transcriptional level of yeast antioxidant enzyme genes such as superoxide dismutase (SOD) and catalase. In the present study, yeast cells were pretreated with various concentrations of NAC and/or irradiated with various doses of gamma rays. The cell viability was measured by counting the cell forming unit (CFU). The quantitative real-time PCR was performed for analysis of gene expression of SOD and catalase. The viability of irradiated cells was not improved by pretreatment with NAC. Ionizing radiation with 100 Gy highly induced the gene expression of antioxidant enzymes. In the irradiated group with NAC pretreatment, the gene expression of SOD and catalase was gradually reduced with the increased concentrations of NAC. These results indicate that NAC can act as a useful antioxidant to scavenge reactive oxygen species in vivo, but does not protect cells against IR-induced cell death in S. cerevisiae.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.256-262
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• 2022

Panax ginseng C. A. Meyer is well known as traditional herbal medicine, and ginseng berries are known to exhibit potential immune-enhancing functions. However, little is known about the in vivo immunomodulatory activity of Korean ginseng berries. In this study, crude Korean ginseng berries polysaccharides (GBP) were isolated and their immunomodulatory activities were investigated using cyclophosphamide (CY)-induced immunosuppressive BALB/c mice. In CY-treated mice, oral administration of GBP (50-500 mg/kg BW) remarkably increased their spleen sizes and spleen indices and activated NK cell activities. GBP also resulted in the proliferation of splenic lymphocytes (coordinating with ConA: plant mitogen which is known to stimulate T-cell or LPS: endotoxin which binds receptor complex in B cells to promote the secretion of pro-inflammatory cytokines) in a dose-dependent manner. In addition, GBP significantly stimulated mRNA expression levels of immune-associated genes including interleukin-1β (IL-1β), IL-2, IL-4, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), toll-like receptor 4 (TLR-4), and cyclooxygenase-2 (COX-2) in CY-treated mice. These results indicate that GBP is involved in immune effects against CY-induced immunosuppression. Thus, GBP could be developed as an immunomodulation agent for medicinal or functional food application.

• Journal of Microbiology and Biotechnology
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• v.33 no.8
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• pp.1030-1038
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• 2023

Lactiplantibacillus plantarum, previously named Lactobacillus plantarum, is a facultative, homofermentative lactic acid bacterium widely distributed in nature. Several Lpb. plantarum strains have been demonstrated to possess good probiotic properties, and Lpb. plantarum HOM3204 is a potential probiotic strain isolated from homemade pickled cabbage plants. In this study, whole-genome sequencing was performed to acquire genetic information and predict the function of HOM3204, which has a circular chromosome of 3,232,697 bp and two plasmids of 48,573 and 17,060 bp, respectively. Moreover, various oxidative stress-related genes were identified in the strain, and its antioxidant activity was evaluated in vitro and in vivo. Compared to reference strains, the intracellular cell-free extracts of Lpb. plantarum HOM3204 at a dose of 10¹⁰ colony-forming units (CFU)/ml in vitro exhibited stronger antioxidant properties, such as total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging rate, superoxide dismutase activity, and glutathione (GSH) content. Daily administration of 10⁹ CFU Lpb. plantarum HOM3204 for 45 days significantly improved the antioxidant function by increasing the glutathione peroxidase activity in the whole blood and GSH concentration in the livers of D-galactose-induced aging mice. These results suggest that Lpb. plantarum HOM3204 can potentially be used as a food ingredient with good antioxidant properties.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.222-226
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• 2003

Purpose: The interaction of the Fas: Fas ligand has been recognized to play an important role in radiation induced apoptosis. The purpose of this study was to investigate the role of Fas and Fas ligand mutations, in radiation-induced apoptosis in vivo. Materials and Methods: Mice with a mutation in the Fas ($C57BL/6J-Fas^{lpr}$) and its normal control (C57BL/6J) and the Fas ligand ($C3H/HeJ-Fas^{gld}$) and its normal control (C3H/HeJ), were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed at various time intervals, and their spleens collected. Tissue sample was stained with hematoxylin-eosin, and the numbers of apoptotic cells scored. The regulating molecules of apoptosis including the p53, Bcl-2, Bax, $Bcl-X_L\;and\;Bcl-X_s$ genes were also analyzed by Western blotting. Results: With 2.5 Gy and 10 Gy of irradiation, the levels of apoptosis were lower in the $C57BL/6J-Fas^{lpr}\;and\;C3H/HeJ-Fas^{gld}$ mice than in the control mice (p<0.05). With the expression of apoptosis regulating molecules, the Bax was increased in both the C57BL/6J and C3H/HeJ mice in response to radiation; the peak levels of Bax in the C57BL6J and C3H/HeJ were 3 and 3.3-fold higher after 8hr, respectively. However the Bax was not increased in either the $C57BL/6J-Fas^{lpr}\;or\;C3H/HeJ-Fas^{gld}$mice. The p53, Bcl-X_L,\;Bcl-X_S$and Bcl-2 showed no significant changes in the $C57BL/6J-Fas^{lpr},\;C3H/HeJ-Fas^{gld}$, C57BL/6J and C3H/HeJ mice. Conclusion: The levels of radiation-induced apoptosis were lower in the lpr and gld, than the control mice, which seemed to be related to the level of Bax activation due to the radiation in the lpr and gld mice. This result suggests that Fas/Fas L plays an important role in radiation-induced apoptosis in vivo.