• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.794-802
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• 2021

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.

• 대한한의학방제학회지
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• 제31권2호
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• pp.111-124
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• 2023

Objectives : Oxidative stress is an important cause of many diseases including liver injury. Therefore, adequate regulation of oxidative stress plays a pivotal role in maintaining liver function. Until recently, there has been no studies on the hepatoprotective effect of Samchulgeonbi-tang (SCGBT). Therefore, the hepatoprotective effect of SCGBT was investigated in HepG2 cells. In this study, oxidative stress was induced by arachidonic acid (AA) and iron. Methods : To analyze the hepatoprotective effects of SCGBT against oxidative stress induced by AA + iron, the cell viability, apoptosis-related proteins and intracellular ROS, glutathione (GSH), and mitochondrial membrane permeability (MMP) were measured. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) transcription activation and expressions of Nrf2 target gene were analyzed through immunoblot analysis. Results : SCGBT increased the cell viability from AA + iron - induced cell death and inhibited apoptosis by regulating apoptosis related proteins. SCGBT protected cells by inhibiting ROS production, GSH depletion, and MMP degradation against AA + iron induced oxidative stress. Furthermore, Nrf2 activation was increased by SCGBT, and the Nrf2 target genes were also activated by SCGBT. Conclusions : These results suggest that the SCGBT has a hepatocyte protection effect and antioxidant effect from AA + iron induced oxidative stress.

• 대한본초학회지
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• 제35권3호
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• pp.17-24
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• 2020

Objectives : The objective of this study was to evaluate the gastric protective effect of Curcuma Longae Rhizoma (CLR) in 150 mM HCl/60% ethanol induced gastric ulcer (GU) in mice. Methods : Forty ICR mice were divided into five groups (n=8/Group): Nor group; Normal, Veh group; GU control, SC group; GU + sucralfate 10 mg/kg, CL; GU + CLR 30% ethanol extract 100 mg/kg, CH group; GU + CLR 30% ethanol extract 200 mg/kg. Then, mice were orally administered with 150 mM HCl/60% ethanol and caused GU. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : CLR showed significance scavenging effects in 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities (DPPH IC₅₀; 78.18 ± 0.60 ㎍/㎖, ABTS IC₅₀; 55.91 ± 1.86 ㎍/㎖). CLR significance reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) via nuclear factor kappa B (NF-κB) inactivation. In addition, the activation of nuclear factor erythroid2-related factor 2 (Nrf2) significantly led to up-regulation of anti-oxidant enzymes including factors heme oxygenase-1 (HO-1), super oxide dismutase (SOD), and glutathione peroxidase-1/2 (GPx-1/2). Conclusions : Our discovery provides that CLR possesses anti-oxidant and anti-inflammatory effects. Hence, CLR may ameliorate the development of gastric ulcer though the inhibition of NF-κB inflammatory pathway and the elevation of Nrf2 anti-oxidant pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2911-2916
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• 2014

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.481-492
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• 2020

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis. Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.447-454
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• 2022

Few studies have evaluated the role of autophagy in the development of oxaliplatin (OXT) resistance in colon cancer cells. In this study, we compared the role of autophagy between SNU-C5 colon cancer cells and OXT-resistant SNU-C5 (SNU-C5/OXTR) cells. At the same concentration of OXT, the cytotoxicity of OXT or apoptosis was significantly reduced in SNU-C5/OXTR cells compared with that in SNU-C5 cells. Compared with SNU-C5 cells, SNU-C5/OXTR cells exhibited low levels of autophagy. The expression level of important autophagy proteins, such as autophagy-related protein 5 (Atg5), beclin-1, Atg7, microtubule-associated proteins 1A/1B light chain 3B I (LC3-I), and LC3-II, was significantly lower in SNU-C5/OXTR cells than that in SNU-C5 cells. The expression level of the autophagy-essential protein p62 was also lower in SNU-C5/OXTR cells than in SNU-C5 cells. In SNU-C5/OXTR cells, the production of intracellular reactive oxygen species (ROS) was significantly higher than that in SNU-C5 cells, and treatment with the ROS scavenger N-acetylcysteine restored the reduced autophagy levels. Furthermore, the expression of antioxidant-related nuclear factor erythroid 2-related factor 2 transcription factor, heme oxygenase-1, and Cu/Zn superoxide dismutase were also significantly increased in SNU-C5/OXTR cells. These findings suggest that autophagy is significantly reduced in SNU-C5/OXTR cells compared with SNU-C5 cells, which may be related to the production of ROS in OXT-resistant cells.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Nutrition Research and Practice
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• 제7권6호
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• pp.475-480
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• 2013

The purpose of this study was to determine the antioxidant effect of fucoxanthin. After rats were fed a normal fat diet (NF), high fat diet (HF), and high fat with 0.2% fucoxanthin diet (HF + Fxn) for 4 weeks, the markers of oxidative stress and antioxidant capacity like lipid peroxidation, plasma total antioxidant capacity (TAC), and activities of antioxidant enzymes (catalase, superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px)) were determined. mRNA expression of transcription factor, nuclear erythroid factor like 2 (Nrf2), and its target genes such as NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase-1 (HO-1) were also determined. Mean weight gain in the HF + Fxn group was lower, without statistical significance, and the total food intake in the HF + Fxn group was lower than that in the HF group (P < 0.05). The activity of GSH-Px (P < 0.05) in plasma was significantly higher in the HF + Fxn group than those in the HF group (P < 0.05). In the liver, the activities of catalase (P < 0.05) and GSH-Px (P < 0.05) in the HF + Fxn group were significantly higher than those in the HF group. Plasma TAC level was significantly higher in the HF + Fxn group than that in the HF group (P < 0.05). Lipid peroxidation in plasma tended to be lower without statistical significance. Fucoxanthin supplements were shown to have higher mRNA expression of Nrf2 and NQO1 than those in the high fat diet only group (P < 0.05). In conclusion, supplementation of fucoxanthin improved the antioxidant capacity, depleted by high fat diet, by activating the Nrf2 pathway and its downstream target gene NQO1. Therefore, supplementation of fucoxanthin, especially for those who consume high fat in their diet, may benefit from reduced risk of oxidative stress.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• 한방재활의학과학회지
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• 제31권1호
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• pp.17-32
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• 2021

Objectives The present study was designed to find out the therapeutic effects and possible underlying mechanism of Buja-tang, a herbal complex formula on experimental monosodium iodoacetate (MIA)-induced osteoarthritis. Methods Osteoarthritis models were created via intra-joint injection of MIA (50 μL with 80 mg/mL) in rats. Rats were divided into five groups and each group consisted of seven. Normal group was not injected MIA and did a normal diet. Control group injected MIA and received distilled water. Indo injected MIA and oral administration of 5 mg/kg of indomethacin. BJTL injected MIA and oral administration of 100 mg/kg of Buja-tang. BJTH injected MIA and oral administration of 200 mg/kg of Buja-tang. We analyzed weight-bearing ability of hind paws, oxidative stress related factor, antioxidant protein, inflammatory protein, inflammatory messenger and cytokine in joint tissue. Pathological observation of knee cartilage tissue structures was also performed with hematoxylin & eosin and safranin-O chromosomes. Results Weight-bearing ability of hind paws showed a tendency to reduce pain. The incidence of nicotinamide adenine dinucleotide phosphate oxidase and p22phox in articular tissue was significantly reduced, and the incidence of nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 and superoxide dismutases was significantly increased. The incidence of phosphorylated inhibitor of κBα, nuclear factor-kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β decreased significantly. In pathological observation, cartilage tissue damaged by MIAs in biopsy has significantly recovered from Buja-tang administration. Conclusions Buja-tang has anti-inflammation, antioxidation and pain relief effects. So this is thought to inhibit the progress of osteoarthritis in rat caused by the MIA.