Publications by authors named "In-Chul Lee"

85 Publications

Four-Week Repeated Intravenous Dose Toxicity of Self-Assembled-Micelle Inhibitory RNA-Targeting Amphiregulin in Mice.

Int J Toxicol 2021 Jul 21:10915818211031241. Epub 2021 Jul 21.

College of Veterinary Medicine, 34931Chonnam National University, Gwangju, Republic of Korea.

The present study investigated the potential subchronic toxicity of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) in mice. The test reagent was administered once-daily by intravenous injection for 4 weeks at 0, 100, 200, or 300 mg/kg/day doses. Additional recovery groups (vehicle control and high dose groups) were observed for a 2-week recovery period. During the test period, mortality, clinical signs, body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. An increase in the percentages of basophil and large unstained cells was observed in the 200 and 300 mg/kg/day groups of both sexes. In addition, the absolute and relative weights of the spleen were higher in males given 300 mg/kg/day relative to the concurrent controls. However, these findings were considered of no toxicological significance because the changes were minimal, were not accompanied by other relevant results (eg, correlating microscopic changes), and were not observed at the end of the 2-week recovery period indicating recovery of the findings. Based on the results, SAMiRNA-AREG did not cause treatment-related adverse effects at dose levels of up to 300 mg/kg/day in mice after 4-week repeated intravenous doses. Under these conditions, the no-observed-adverse-effect level of the SAMiRNA-AREG was ≥300 mg/kg/day in both sexes and no target organs were identified.
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http://dx.doi.org/10.1177/10915818211031241DOI Listing
July 2021

Safety pharmacology of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle platform.

Toxicol Rep 2021 31;8:839-845. Epub 2021 Mar 31.

siRNAgen Therapeutics and Bioneer Corporation, Daejeon, 34302, Republic of Korea.

The present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300 mg/kg and 100 mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200 μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5 h (30 min) post-dose at both sexes in mice, with a single 300 mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1 h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200 μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.
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http://dx.doi.org/10.1016/j.toxrep.2021.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065257PMC
March 2021

Genotoxicity evaluation of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle for the treatment of fibrotic disease.

Drug Chem Toxicol 2021 Apr 27:1-7. Epub 2021 Apr 27.

College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.

The self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) is a novel small-interfering RNA (siRNA) nanoparticle that is used for treatment of pulmonary fibrosis. We investigated the potential genotoxicity of SAMiRNA-AREG based on the guidelines published by the Organization for Economic Cooperation and Development. In the bacterial reverse mutation assay (Ames test), SAMiRNA-AREG did not induce mutations in TA100, TA1535, TA98, and TA1537 and WP2uvrA at concentrations of up to 3000 μg/plate with or without metabolic activation. The SAMiRNA-AREG (concentrations up to 500 μg/mL) did not induce chromosomal aberrations in cultured Chinese hamster lung cells with or without metabolic activation. In the mouse bone marrow micronucleus assay, the SAMiRNA-AREG (concentrations up to 300 mg/kg body weight) did not affect the proportions of polychromatic erythrocytes and total erythrocytes, nor did it increase the number of micronucleated polychromatic erythrocytes in ICR mice. Collectively, these results suggest that SAMiRNA-AREG is safe with regard to genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of SAMiRNA-AREG as a potential therapeutic agent for pharmaceutical development.
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http://dx.doi.org/10.1080/01480545.2021.1908003DOI Listing
April 2021

Alnus hirsuta (Spach) Rupr. Attenuates Airway Inflammation and Mucus Overproduction in a Murine Model of Ovalbumin-Challenged Asthma.

Front Pharmacol 2021 10;12:614442. Epub 2021 Feb 10.

Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea.

(Spach) Rupr. (AH), a member of the Betulaceae family, is widely used in Eastern Asia of as a source of medicinal compounds for the treatment of hemorrhage, diarrhea, and alcoholism. In this study, we investigated the protective effects of a methanolic extract of AH branches against airway inflammation and mucus production in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in an ovalbumin (OVA)-challenged allergic asthma mouse model. Female BALB/c mice were injected with OVA (40 μg) and aluminum hydroxide (2 mg) on days 0 and 14 to induce allergic airway inflammation. The mice were then challenged with 1% OVA from days 21-23. Mice were treated with AH (50 and 100 mg/kg/day; 2% DMSO) or dexamethasone (positive control; 3 mg/kg/day) from days 18-23. AH treatment effectively attenuated airway resistance/hyperresponsiveness and reduced levels of T helper type 2 (Th2) cytokines, eotaxins, and number of inflammatory cells in bronchoalveolar lavage fluid, and immunoglobulin E in serums of OVA-challenged mice. In histological analysis, AH treatment significantly inhibited airway inflammation and mucus production in OVA-challenged mice. AH treatment downregulated the phosphorylation of I kappa B-alpha, p65 nuclear factor-kappa B (p65NF-κB), and mitogen-activated protein kinases with suppression of mucin 5AC (MUC5AC) in lung tissue. Moreover, AH treatment decreased the levels of pro-inflammatory cytokines and Th2 cytokines, as well as MUC5AC expression, and inhibited the phosphorylation of p65NF-κB in TNF-α-stimulated NCI-H292 cells. These results indicate that AH might represent a useful therapeutic agent for the treatment of allergic asthma.
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http://dx.doi.org/10.3389/fphar.2021.614442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902870PMC
February 2021

Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity.

Antioxidants (Basel) 2021 Feb 1;10(2). Epub 2021 Feb 1.

Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea.

Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the antiviral activity of native HDL with glycated HDL via fructosylation and native low-density lipoproteins (LDL). After 72 h of fructosylation, glycated HDL showed a typical multimerized protein pattern with an elevation of yellowish fluorescence. Glycated HDL showed a smaller particle size with an ambiguous shape and a loss of paraoxonase activity up to 51% compared to native HDL. The phagocytosis of acetylated LDL was accelerated 1.3-fold by glycated HDL than native HDL. Native HDL showed 1.7 times higher cell viability and 3.6 times higher cytopathic effect (CPE) inhibition activity against SARS-CoV-2 than that of glycated HDL under 60 μg/mL (approximately final 2.2 μM) in a Vero E6 cell. Native HDL showed EC = 52.1 ± 1.1 μg/mL (approximately final 1.8 μM) for the CPE and CC = 79.4 ± 1.5 μg/mL (around 2.8 μM). The selective index (SI) of native HDL was calculated to be 1.52. In conclusion, native HDL shows potent antiviral activity against SARS-CoV-2 without cytotoxicity, while the glycation of HDL impairs its antiviral activity. These results may explain why patients with diabetes mellitus or hypertension are more sensitive to a COVID-19 infection and have a higher risk of mortality.
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http://dx.doi.org/10.3390/antiox10020209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912765PMC
February 2021

Colorimetric Detection of SARS-CoV-2 and Drug-Resistant pH1N1 Using CRISPR/dCas9.

ACS Sens 2020 12 3;5(12):4017-4026. Epub 2020 Dec 3.

Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

Viruses have been a continuous threat to human beings. The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a pandemic that is still ongoing worldwide. Previous pandemic influenza A virus (pH1N1) might be re-emerging through a drug-resistant mutation. We report a colorimetric viral detection method based on the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 endonuclease dead (dCas9) system. In this method, RNA in the viral lysate was directly recognized by the CRISPR/dCas9 system with biotin-protospacer adjacent motif (PAM)-presenting oligonucleotide (PAMmer). Streptavidin-horseradish peroxidase then bound to biotin-PAMmer, inducing a color change through the oxidation of 3,3',5,5'-tetramethylbenzidine. Using the developed method, we successfully identified SARS-CoV-2, pH1N1, and pH1N1/H275Y viruses by the naked eye. Moreover, the detection of viruses in human nasopharyngeal aspirates and sputum was demonstrated. Finally, clinical samples from COVID-19 patients led to a successful diagnosis. We anticipate that the current method can be employed for simple and accurate diagnosis of viruses.
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http://dx.doi.org/10.1021/acssensors.0c01929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724983PMC
December 2020

Evaluation of 13-week subchronic toxicity of Platycodon grandiflorus (Jacq.) A.DC. root extract in rats.

J Ethnopharmacol 2021 Mar 25;267:113621. Epub 2020 Nov 25.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Platycodi radix is widely used in traditional herbal medicine for bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. However, data on safety of Platycodi radix are insufficient.

Aim Of The Study: The present study was performed to evaluate the potential subchronic toxicity of Platycodi radix water extract through a 13-week repeated oral dose experiment in Sprague-Dawley rats.

Materials And Methods: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 300, 1000, and 3000 mg/kg/day of Platycodi radix water extract and a vehicle control group receiving sterile distilled water for 13 weeks.

Results: Repeated oral administration of the Platycodi radix water extract to rats resulted in an increased incidence of centrilobular hepatocellular hypertrophy in the liver, diffuse follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia of the limiting ridge in the stomach at dose levels of ≥500 mg/kg/day of both genders. However, these findings are considered be adaptive non-adverse changes because these findings were observed without organ weight change or clinical pathology alterations. No treatment-related effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested.

Conclusion: Under the present experimental conditions, the no-observed-adverse-effect level of the Platycodi radix water extract was considered to be ≥ 3000 mg/kg/day in rats, and no target organs were identified.
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http://dx.doi.org/10.1016/j.jep.2020.113621DOI Listing
March 2021

Oleanolic Acid Acetate Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis in Mice by Regulating Toll-Like Receptor 2 Signaling.

Front Pharmacol 2020 3;11:556391. Epub 2020 Sep 3.

Functional Biomaterials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea.

Toll-like receptor 2 (TLR2) is expressed by several immune cells in the central nervous system and plays an important role in neuroinflammation. TLR2 upregulation has been reported in multiple sclerosis patients and in experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Therefore, modulating TLR2 signaling can be an effective treatment strategy against MS. Oleanolic acid acetate (OAA) has antiinflammatory and immunomodulatory effects. Hence, this study aimed to examine the effects of OAA on TLR2 signaling and neuroinflammation in EAE. EAE was induced in C57/BL6 mice using synthesized myelin oligodendrocyte glycoprotein (MOG) peptide, and OAA was administered daily. Hind limb paralysis and inflammatory cell infiltration were observed in the spinal cords of EAE mice. Moreover, T-cell proliferation was significantly stimulated in splenic cells from EAE mice. The expression of proinflammatory cytokines in the spinal cord was upregulated, and their serum protein levels were increased in EAE mice. Furthermore, upregulation of TLR2 and downstream signaling molecules was observed in the spinal cord. These pathological changes were reversed by OAA treatment. Our results suggest that OAA might have promising therapeutic properties and that the TLR signaling pathway is an effective therapeutic target against multiple sclerosis.
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http://dx.doi.org/10.3389/fphar.2020.556391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494849PMC
September 2020

Attenuates Oxidative Stress and Airway Inflammation in a Murine Model of Ovalbumin-Challenged Asthma.

Antioxidants (Basel) 2020 Jun 27;9(7). Epub 2020 Jun 27.

Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeollabuk-do 56212, Korea.

is widespread in northeast Asia and used for treatment of improvement of blood circulation and anti-inflammation. In this study, we investigated anti-inflammatory and anti-oxidant effects of the methanolic extract of leaves (LOL) in an ovalbumin (OVA)-challenged allergic asthma model and tumor necrosis factor (TNF)-α-stimulated NCI-H292 cell. Female BALB/c mice were sensitized with OVA by intraperitoneal injection on days 0 and 14, and airway-challenged with OVA from days 21 to 23. Mice were administered 50 and 100 mg/kg of LOL by oral gavage 1 h before the challenge. LOL treatment effectively decreased airway hyper-responsiveness and inhibited inflammatory cell recruitment, Th2 cytokines, mucin 5AC (MUC5AC) in bronchoalveolar lavage fluid in OVA-challenged mice, which were accompanied by marked suppression of airway inflammation and mucus production in the lung tissue. LOL pretreatment inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) with suppression of activator protein (AP)-1 and MUC5AC in the lung tissue. LOL also down-regulated expression of inflammatory cytokines, and inhibited the activation of NF-κB in TNF-α-stimulated NCI-H292 cells. LOL elevated the translocation of nuclear factor-erythroid 2-related factor (Nrf-2) into nucleus concurrent with increase of heme oxyngenase-1 (HO-1) and NAD(P)H quinine oxidoreductase 1 (NQO1). Moreover, LOL treatment exhibited a marked increase in the anti-oxidant enzymes activities, whereas effectively suppressed the production of reactive oxygen species and nitric oxide, as well as lipid peroxidation in lung tissue of OVA-challenged mice and TNF-α-stimulated NCI-H292 cells. These findings suggest that LOL might serve as a therapeutic agent for the treatment of allergic asthma.
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http://dx.doi.org/10.3390/antiox9070563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402094PMC
June 2020

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling.

Cells 2020 03 10;9(3). Epub 2020 Mar 10.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea.

Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.
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http://dx.doi.org/10.3390/cells9030678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140632PMC
March 2020

var. Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells.

Antioxidants (Basel) 2020 Feb 26;9(3). Epub 2020 Feb 26.

Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeollabuk-do 56212, Korea.

var. (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.
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http://dx.doi.org/10.3390/antiox9030198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139931PMC
February 2020

Suppressive effects of aloin on polyphosphate-mediated vascular inflammatory responses.

J Asian Nat Prod Res 2021 Jan 20;23(1):89-99. Epub 2020 Feb 20.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.

Human endothelial cells-derived polyphosphate (PolyP) is one of the pro-inflammatory mediators as suggested by the previous reports. Aloin is the major anthraquinone glycoside obtained from the species and exhibits anti-inflammatory and anti-oxidative activities. Aloin inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules, and adhesion/migration of leukocyte to HUVEC. PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by aloin in HUVECs. These anti-inflammatory functions of aloin were confirmed in PolyP-injected mice. In conclusion, based on the anti-inflammatory effects of aloin in PolyP-mediated septic response, aloin has therapeutic potential for various systemic inflammatory diseases.
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http://dx.doi.org/10.1080/10286020.2020.1724969DOI Listing
January 2021

Inhibitory effects of aloin on TGFBIp-mediated septic responses.

J Asian Nat Prod Res 2021 Feb 24;23(2):189-203. Epub 2020 Jan 24.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.

Aloin is the major anthraquinone glycoside obtained from the species. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein and released by primary human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. We hypothesized that aloin could reduce TGFBIp-mediated severe inflammatory responses in HUVECs and mice. Aloin effectively inhibited lipopolysaccharide (LPS)-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. Aloin suppressed TGFBIp-induced sepsis lethality and pulmonary injury. Therefore, aloin is a potential therapeutic agent for various severe vascular inflammatory diseases, with inhibition of the TGFBIp signaling pathway as the mechanism of action. [Formula: see text].
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http://dx.doi.org/10.1080/10286020.2019.1711066DOI Listing
February 2021

Anti-Oxidative and Anti-Inflammatory Activity of Kenya Grade AA Green Coffee Bean Extracts.

Iran J Public Health 2019 Nov;48(11):2025-2034

Sports and Health Care Major, College of Humanities and Arts, Korea National University of Transportation, Chungju-si, Korea.

Background: Kenya AA green coffee bean extracts were tested for natural ingredients used for anti-oxidative and anti-inflammatory purposes in cosmetic products.

Methods: Anti-oxidative activities were measured by total polyphenol, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Anti-inflammatory activities were evaluated via nitric oxide (NO) assays, and through quantification of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) protein expression by western blotting. Data analyses were performed using independent Student's t-tests, with statistical significance set at P < 0.05.

Results: Total polyphenol content of water and ethanol extract was 169.0 ± 3.1 mg and 300.34 ± 16.6 mg tannic acid/g dry weight, respectively. The DPPH and ABTS radical scavenging activities of all the extracts were significantly increased in a concentration-dependent manner. Kenya AA green coffee bean extracts were toxic at a concentration of 1,000 μg/mL in RAW 264.7 cells. Anti-inflammatory activity as determined by NO assay showed that lipopolysaccharide (LPS)-induced NO was significantly inhibited following treatment with Kenya AA green coffee bean extracts in a concentration-dependent manner. iNOS and COX-2 protein expression was also significantly inhibited following treatment.

Conclusion: These results highlight the potential of Kenya AA green coffee bean extracts as a naturally active anti-inflammatory agent in cosmetic products.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961199PMC
November 2019

Hepatoprotective effects of vicenin-2 and scolymoside through the modulation of inflammatory pathways.

J Nat Med 2020 Jan 26;74(1):90-97. Epub 2019 Jul 26.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu, 41566, Republic of Korea.

The aim of this study was to investigate the effects of two structurally related flavonoids found in Cyclopia subternata, vicenin-2 (VCN) and scolymoside (SCL) on lipopolysaccharide (LPS)-induced liver failure in mice and to elucidate underlying mechanisms. Mice were treated intravenously with VCN or SCL at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of alanine transaminase, aspartate transaminase, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression; these effects of LPS were inhibited by VCN or SCL. It also attenuated the LPS-induced activation of myeloid differentiation primary response gene 88 and TLR-associated activator of interferon-dependent signaling pathways of the TLR system. Our results suggest that VCN or SCL protects against LPS-induced liver damage by inhibiting the TLR-mediated inflammatory pathway, indicating its potential to treat liver diseases.
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http://dx.doi.org/10.1007/s11418-019-01348-xDOI Listing
January 2020

Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho.

Food Chem Toxicol 2019 Jul 27;129:201-210. Epub 2019 Apr 27.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea. Electronic address:

This study investigated the protective effects of melatonin (MT) against cisplatin (CP)-induced acute kidney injury in rats as well as its possible mechanism of action associated with anti-aging protein Klotho. The following four experimental groups were evaluated: vehicle control, CP (7 mg/kg), CP&MT20 (20 mg/kg/day), and CP&MT40 (40 mg/kg/day). The concomitant administration of MT significantly ameliorated CP-induced acute kidney injury in rats, as evidenced by increased kidney weight, increased serum levels of blood urea nitrogen and creatinine, and increased incidence of histopathological alterations with renal tubular cell apoptosis. In addition, MT treatment protected kidney tissue against oxidative damages and significantly upregulated the expression level of Klotho decreased by CP treatment, resulting in reduced phosphorylation of protein kinase B (AKT) and forkhead box O (FOXO) as well as reduced expression levels of B-cell lymphoma 2-associated X protein (Bax) and caspase-3. MT not only partially regulated oxidative stress via AKT/FOXO signaling, but also reduced apoptosis caused by CP by inhibiting the Bax/caspase-3 pathway. Our results indicated that MT could prevent acute kidney injury induced by CP in rats, presumably through upregulating the expression of Klotho, resulting in elevated anti-oxidant and anti-apoptotic properties.
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http://dx.doi.org/10.1016/j.fct.2019.04.049DOI Listing
July 2019

S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model.

Int Immunopharmacol 2019 Mar 9;68:124-130. Epub 2019 Jan 9.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea. Electronic address:

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.
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http://dx.doi.org/10.1016/j.intimp.2019.01.001DOI Listing
March 2019

Pelargonidin Protects Against Renal Injury in a Mouse Model of Sepsis.

J Med Food 2019 Jan 30;22(1):57-61. Epub 2018 Aug 30.

2 College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu, Korea.

Pelargonidin (PEL) is a well-known red pigment found in plants, and it has been reported to have important biological activities that are potentially beneficial for human health. This study was initiated to determine whether PEL could modulate renal functional damage in a mouse model of sepsis, and to elucidate the underlying mechanisms. The potential of PEL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase (GSH-Px) activity, catalase activity, and superoxide dismutase (SOD) activity. Treatment with PEL resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, PEL inhibited nuclear factor-κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. PEL treatment also reduced the plasma levels of interleukin-6 and tumor necrosis factor-α reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of SOD, GSH-Px, and catalase in kidney tissues. These results suggested that PEL protects mice against sepsis-triggered renal injury.
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http://dx.doi.org/10.1089/jmf.2018.4230DOI Listing
January 2019

Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma.

Front Pharmacol 2018 8;9:906. Epub 2018 Aug 8.

K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, South Korea.

Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune response of animals, OVA sensitization was performed on days 0 and 14. LB (250 or 500 μg/kg) was administered by oral gavage on days 18 to 23, and the OVA challenge was performed using an ultrasonic nebulizer on days 21 to 23. Plethysmography showed airway hyperresponsiveness (AHR) on day 24. LB treatment effectively decreased inflammatory cell recruitment, T-helper type 2 cytokines in the bronchoalveolar lavage fluid, and immunoglobulin (Ig) E in the serum of the animals with OVA-induced asthma, which was accompanied by a marked reduction in AHR. It also decreased airway inflammation, mucus hypersecretion, phosphorylation of nuclear transcription factor-kappa-B (NF-κB), and expression of activating protein (AP)-1 and mucin 5AC (MUC5AC). Overall, LB effectively attenuated the pathophysiological changes of asthma and its effects appear related to a reduction in the phosphorylation of NF-κB and the expression of AP-1. Thus, our results suggest that LB has a potential to treat allergic asthma.
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http://dx.doi.org/10.3389/fphar.2018.00906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092601PMC
August 2018

Design, synthesis, and evaluation of curcumin analogues as potential inhibitors of bacterial sialidase.

J Enzyme Inhib Med Chem 2018 Dec;33(1):1256-1265

b Natural Product Material Research Center , Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.

Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC = 0.2 ± 0.1 µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections.
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http://dx.doi.org/10.1080/14756366.2018.1488695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104608PMC
December 2018

Copper nanoparticles induce early fibrotic changes in the liver via TGF-β/Smad signaling and cause immunosuppressive effects in rats.

Nanotoxicology 2018 08 30;12(6):637-651. Epub 2018 May 30.

b College of Veterinary Medicine BK21 Plus Team , Chonnam National University , Gwangju , Republic of Korea.

Copper nanoparticles (Cu NPs) have various uses, including as additives in polymers/plastics, lubricants for metallic coating, and biomedical applications. We investigated the role of transforming growth factor (TGF)-β1 signaling in hepatic damage caused by Cu NPs and explored the effects of a 28-day repeated oral administration to Cu NPs on the immune response. The exposure to Cu NPs caused a dose-dependent increase in Cu levels in the liver and spleen. Cu NPs caused hepatic damage and markedly increased oxidative stress in liver tissues. Cu NPs induced activation of TGF-β1/Smad signaling by induction of vascular endothelial growth factor and matrix metalloproteinase-9. Exposure to Cu NPs also induced activation of Smad-independent pathways, phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt/FoxO3. Consistent with the activation of TGF-β1/Smad-dependent and -independent pathways, Cu NPs markedly increased the deposition and induction of extracellular matrix components, α-smooth muscle actin, and collagens in liver tissues. In addition, repeated exposure to Cu NPs suppressed the proliferation of mitogenically stimulated T- or B-lymphocytes and decreased CD3 (particularly, CD3CD4CD8) and CD45 population, followed by decreased levels of immunoglobulins and Th1/Th2 type cytokines. Collectively, Cu NPs caused hepatic damage and induced pro-fibrotic changes, which were closely related to the activation of oxidative stress-mediated TGF-β1/Smad-dependent and -independent pathways (MAPKs and Akt/FoxO3). We confirmed the immunosuppressive effect of Cu NPs via the inhibition of mitogen-stimulated spleen-derived lymphocyte proliferation and suppression of B- or T-lymphocyte-mediated immune responses.
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http://dx.doi.org/10.1080/17435390.2018.1472313DOI Listing
August 2018

Copper oxide nanoparticles induce collagen deposition via TGF-β1/Smad3 signaling in human airway epithelial cells.

Nanotoxicology 2018 04 31;12(3):239-250. Epub 2018 Jan 31.

a College of Veterinary Medicine (BK21 Plus Project Team) , Chonnam National University , Gwangju , Republic of Korea.

Use and application of nanoparticles has increased in recent years. Copper oxide nanoparticles (CuONPs) are one of the most common types of nanoparticles, and they are mainly used as catalysts and preservatives. However, limited toxicity data are available on the toxicity of CuONPs to the respiratory system. We investigated fibrotic responses induced by CuONPs in the respiratory tract and elucidated its underlying mechanism of action in vivo and in vitro experiments. In the mouse model, CuONPs exposure markedly increased transforming growth factor-β1 (TGF-β1) and collagen I expression and Smad3 phosphorylation, combined with elevation of inflammatory mediators including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). These alterations were also observed in histological analysis of lung tissue. CuONPs markedly increased inflammatory responses and collagen deposition, accompanied by the elevation of TGF-β1 and collagen I expression in lung tissue. In addition, CuONPs-treated H292 cells showed significantly increased mRNA and protein production of TGF-β1, collagen I, IL-6, and TNF-α; this response was markedly decreased by treatment of a TGF-β1 inhibitor (SB-431542). Taken together, CuONPs induced fibrotic responses in the respiratory tract, closely related to TGF-β1/Smad3 signaling. Therefore, our results raise the necessity of further investigation for the present state of its risk by providing useful information of the toxicity of CuONPs.
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http://dx.doi.org/10.1080/17435390.2018.1432778DOI Listing
April 2018

The Protein Trio RPK1-CaM4-RbohF Mediates Transient Superoxide Production to Trigger Age-Dependent Cell Death in Arabidopsis.

Cell Rep 2017 Dec;21(12):3373-3380

Center for Plant Aging Research, Institute for Basic Science (IBS), Daegu 42988, Republic of Korea; Department of New Biology, DGIST, Daegu 42988, Republic of Korea. Electronic address:

Reactive oxygen species (ROS) are inevitable by-products of aerobic metabolic processes, causing non-specific oxidative damage and also acting as second messengers. Superoxide is a short-lived ROS that functions in various cellular responses, including aging and cell death. However, it is unclear as to how superoxide brings about age-dependent cell death and senescence. Here, we show that the accumulation and signaling of superoxide are mediated by three Arabidopsis proteins-RPK1, CaM4, and RbohF-which trigger subsequent cellular events leading to age-dependent cell death. We demonstrate that the NADPH oxidase RbohF is responsible for RPK1-mediated transient accumulation of superoxide, SIRK kinase induction, and cell death, all of which are positively regulated by CaM4. RPK1 physically interacts with and phosphorylates CaM4, which, in turn, interacts with RbohF. Overall, we demonstrate how the protein trio governs the superoxide accumulation and signaling at the cell surface to control senescence and cell death.
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http://dx.doi.org/10.1016/j.celrep.2017.11.077DOI Listing
December 2017

Melatonin suppresses fibrotic responses induced by cigarette smoke via downregulation of TGF-β1.

Oncotarget 2017 Nov 9;8(56):95692-95703. Epub 2017 Oct 9.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, Gwangju 500-757, Republic of Korea.

Cigarette smoke (CS) is the most important risk factor in the development of chronic obstructive pulmonary disease (COPD). Pulmonary fibrosis is an irreversible response and important feature of COPD. In this study, we investigated the effects of melatonin on fibrotic response in development of COPD using a CS and lipopolysaccharide (LPS) induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid cell line. Mice were exposed to CS for 1 h per day (8 cigarettes per day) from day 1 to day 7 and were treated intranasally with LPS on day 4. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 h before CS exposure. Melatonin decreased the inflammatory cell counts in bronchoalveolar lavage fluid (BALF), with a reduction in transforming growth factor (TGF)-β1. Melatonin inhibited the expression of TGF-β1, collagen I and SMAD3 phosphorylation in lung tissue exposed to CS and LPS. In CSC-stimulated H292 cells, melatonin suppressed the elevated expression of fibrotic mediators induced by CSC treatment. Melatonin reduced the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation in CSC-stimulated H292 cells. In addition, cotreatment with melatonin and TGF-β1 inhibitors significantly limited fibrotic mediators, with greater reductions in the expression of TGF-β1, collagen I, SMAD3 and p38 phosphorylation than those of H292 cells treated with TGF-β1 inhibitor alone. Taken together, melatonin effectively inhibited fibrotic responses induced by CS and LPS exposure, which was related to the downregulation of TGF-β1. Therefore, our results suggest that melatonin may suppress the pulmonary fibrotic response induced by CS.
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http://dx.doi.org/10.18632/oncotarget.21680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707053PMC
November 2017

Antiseptic effects of dabrafenib on TGFBIp-induced septic responses.

Chem Biol Interact 2017 Dec 14;278:92-100. Epub 2017 Oct 14.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:

Transforming growth factor-β-induced protein (TGFBIp), an extracellular protein, is expressed on several cell types in response to TGF-β stimulation. Human umbilical vein endothelial cell (HUVEC)-derived TGFBIp functions as a mediator of sepsis. Screening of bioactive compound libraries is an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases (drug repositioning). Dabrafenib (DAB), a B-Raf inhibitor, was initially used for treating metastatic melanoma. The present study determined whether DAB modulated TGFBIp-mediated septic responses in HUVECs and in mice. Antiseptic functions of DAB were examined by measuring permeability, leukocyte adhesion and migration, and proinflammatory protein activation in TGFBIp-stimulated HUVECs and mice. In addition, beneficial effects of DAB on survival rate were examined using a mouse model of sepsis. We found that DAB inhibited TGFBIp-induced vascular barrier disruption, cell adhesion molecule (CAM) expression, and neutrophil adhesion/transendothelial migration toward human endothelial cells. DAB also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that DAB exerts anti-inflammatory effects by inhibiting hyperpermeability, CAM expression, and leukocyte adhesion and migration, indicating its utility for treating vascular inflammatory diseases.
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http://dx.doi.org/10.1016/j.cbi.2017.10.016DOI Listing
December 2017

Protective effect and mechanism of action of diallyl disulfide against acetaminophen-induced acute hepatotoxicity.

Food Chem Toxicol 2017 Nov 25;109(Pt 1):28-37. Epub 2017 Aug 25.

Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea. Electronic address:

The aim of this study was to investigate the potential protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute hepatotoxicity and elucidate the molecular mechanisms underlying these protective effects in rats. Treatment with AAP caused acute hepatotoxicity manifested by elevated levels of aspartate aminotransferase and alanine aminotransferase with corresponding histopathological changes and high levels of oxidative stress in the livers. AAP treatment also caused hepatocellular apoptosis with phosphorylation of c-Jun-N-terminal protein kinase (JNK). In addition, AAP caused activation of nuclear factor kappaB (NF-κB) concurrent with induction of inflammatory mediators. In contrast, pretreatment with DADS effectively attenuated acute liver injury and oxidative stress caused by AAP. DADS pretreatment suppressed cytochrome P450 2E1 (CYP2E1) levels in a dose-dependent manner and inhibited elevation of CYP2E1 activity induced by AAP. DADS pretreatment suppressed the phosphorylation of JNK and attenuated hepatocellular apoptotic changes. In addition, DADS inhibited the nuclear translocation of NF-κB and subsequent induction of inflammatory mediators. Overall, these results indicate that DADS confers a protective effect against oxidative stress-mediated JNK activation and apoptotic changes caused by AAP in the rat livers. This may be due to its ability to inhibit CYP2E1, enhance antioxidant enzymes activities, and suppress NF-κB activation.
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http://dx.doi.org/10.1016/j.fct.2017.08.029DOI Listing
November 2017

Sulforaphane Reduces HMGB1-Mediated Septic Responses and Improves Survival Rate in Septic Mice.

Am J Chin Med 2017 22;45(6):1253-1271. Epub 2017 Aug 22.

‡ College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. In this study, we examined the effects of SFN on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of SFN were monitored based on its effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of SFN were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. SFN inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. SFN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SFN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in vivo. Our results indicate that SFN is a possible therapeutic agent that can be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
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http://dx.doi.org/10.1142/S0192415X17500690DOI Listing
October 2017

Silibinin inhibits the fibrotic responses induced by cigarette smoke via suppression of TGF-β1/Smad 2/3 signaling.

Food Chem Toxicol 2017 Aug 8;106(Pt A):424-429. Epub 2017 Jun 8.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea. Electronic address:

Cigarette smoke (CS) is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD) which is characterized by chronic inflammation, fibrotic response, and airway obstruction. In this study, we investigated the preventive effects of silibinin, an active constitute of silymarin on CS and lipopolysaccharide (LPS) exposure-induced fibrotic response. Mice were exposed to CS for 1 h per day (8 cigarettes per day) for 4 weeks. On day 12 and 26, mice were treated with LPS intranasally. Silibinin (10 or 20 mg/kg) was administered orally 1 h before CS exposure. Silibinin markedly decreased the inflammatory cell count in the bronchoalveolar lavage fluid, and reduced levels of proinflammatory mediators. Silibinin suppressed CS + LPS-induced collagen deposition in lung tissue, as evidenced via immunohistochemistry and Masson's trichrome stain. Additionally, silibinin effectively inhibited CS + LPS-mediated expression of transforming growth factor-β1 (TGF-β1) and Smad 2/3 phosphorylation. Taken together, our data indicate that silibinin effectively inhibits the fibrotic response induced by CS + LPS exposure, possibly via suppression of TGF-β1/Smad 2/3 signaling, which results in reduced collagen deposition. These findings suggest that silibinin has therapeutic potential for the treatment of COPD.
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http://dx.doi.org/10.1016/j.fct.2017.06.016DOI Listing
August 2017

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

Lab Anim Res 2017 Mar 27;33(1):40-47. Epub 2017 Mar 27.

College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, Gwangju, Korea.

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.
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http://dx.doi.org/10.5625/lar.2017.33.1.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385281PMC
March 2017

Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-κB.

Food Chem Toxicol 2017 Apr 17;102:156-165. Epub 2017 Feb 17.

College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address:

Diallyl disulfide (DADS) is a degradation product of allicin which is contained in garlic. This study investigated the protective effects of DADS against acetaminophen (AAP)-induced nephrotoxicity and the molecular mechanisms of nephroprotective effects in rats. AAP caused severe nephrotoxicity as evidenced by significant increases in renal tubular cell apoptosis, mitochondria-mediated apoptosis, and up-regulation of nuclear transcription factor kappa-B (NF-κB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) in the kidney with histopathological alterations. After AAP administration, glutathione content and activities of catalase, superoxide dismutase, and glutathione reductase were significantly decreased whereas malondialdehyde content was significantly increased, indicating that AAP-induced kidney injury was mediated through oxidative stress. In contrast, DADS pretreatment significantly attenuated AAP-induced nephrotoxic effects, including oxidative damage, histopathological lesions, and apoptotic changes in the kidney. DADS also attenuated AAP-induced up-regulation of NF-κB, Cox-2, and TNF-α in the kidney, and microsomal CYP2E1 expression in liver and kidney. These results indicated that DADS could prevent AAP-induced nephrotoxicity. The protective effects of DADS might be due to its ability to decrease metabolic activation of AAP by inhibiting CYP2E1 and its potent antioxidant, antiapoptotic, and antiinflammatory effects via inhibition of NF-κB.
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http://dx.doi.org/10.1016/j.fct.2017.02.021DOI Listing
April 2017
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