• The Korean Journal of Pain
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• v.34 no.1
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• pp.47-57
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• 2021

Background: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. Methods: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. Results: Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. Conclusions: The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

• The Korea Journal of Herbology
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• v.36 no.2
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• pp.31-42
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• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.21-28
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• 2013

Objectives : The aim of this study was to investigate the neuroprotective effects and mechanisms of Cyperi Rhizoma extracts (CRE) using in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the neuroprotective effect of CRE against 1-methyl-4-phenylpyridinium (MPP+) toxicity using tyrosine hydroxylase immunohistochemistry (IHC) in primary rat mesencephalic dopaminergic neurons. In addition, the effect of CRE was evaluated in mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For evaluations, C57bl/6 mice were orally treated with CRE 50 mg/kg for 5 days and were injected intraperitoneally with MPTP (20 mg/kg) at 2 h intervals on the last day. To identify the CRE affects on MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum of mice, the behavioral tests and IHC analysis were carried out. Also, we conducted nitric oxide (NO) and tumor necrosis factor-alpha (TNF-${\alpha}$) assay in dopaminergic neurons and IHC using glial markers in SNpc of mice to assess the anti-inflammation effects. Results : In primary mesencephalic culture system, CRE protected dopaminergic cells against $10{\mu}M$ MPP+-induced toxicity at 0.2 and $1.0{\mu}g/mL$. In the behavior tests, CRE treated group showed improved motor deteriorations than those in the MPTP only treated group. CRE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, CRE inhibited productions of NO and TNF-${\alpha}$ in dopaminergic culture system and activation of astrocyte and microglia in SNpc of the mice. Conclusion : We concluded that CRE shows anti-parkinsonian effect by protecting dopaminergic neurons against MPP+/MPTP toxicities through anti-inflammatory actions.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.680-687
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• 2022

Objective : The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. Methods : Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. Results : Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. Conclusion : Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.

• The Journal of Internal Korean Medicine
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• v.43 no.3
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• pp.477-484
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• 2022

Objective: The purpose of this study was to report the improvement effect of symptoms of integrative cancer treatment (ICT) on recurrent gallbladder cancer patients. Methods: A 73-year-old patient with recurrent gallbladder cancer visited the Daejeon Korean Medicine Hospital of Daejeon University East West Cancer Center (EWCC) on February 2022. After the diagnosis of gallbladder cancer, the patient underwent cholecystectomy and relapsed during follow-up. After the operation, the cancer recurred during follow-up, and after radiation treatment, she had been receiving ICT since February 2022. The clinical outcomes were measured by X-ray, computed tomography (CT), laboratory findings, including tumor markers (CEA, CA19-9), and numeric rating scales (NRS). Results: After treatment, abdominal pain was relieved from NRS 5 to 2, and abdominal circumference decreased from 74.5 to 67. During and after treatment, we found neither hepatotoxicity nor nephrotoxicity in the laboratory findings. Conclusion: This case study suggests that ICT may improve symptoms in patients with gallbladder cancer.

• Animal Bioscience
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• v.35 no.4
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• pp.605-613
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• 2022

Objective: The objective was to evaluate the efficacy of increasing supplementation of Yarrowia lipolytica (YL) up to 3.0% replacing 1.6% poultry fat and 0.9% blood plasma for growth performance, intestinal health and nutrient digestibility of diets fed to nursery pigs. Methods: Twenty-four pigs weaned at 24 d of age (initial body weight at 7.2±0.6 kg) were allotted to three dietary treatments (n = 8) based on the randomized complete block. The diets with supplementation of YL (0.0%, 1.5%, and 3.0%, replacing poultry fat and blood plasma up to 1.6% and 0.9%, respectively) were fed for 21 d. Feed intake and body weight were recorded at d 0, 10, and 21. Fecal score was recorded at every odd day from d 3 to 19. Pigs were euthanized on d 21 to collect proximal and distal jejunal mucosa to measure intestinal health markers including tumor necrosis factor-alpha, interleukin-8, immunoglobulin A and immunoglobulin G. Ileal digesta was collected for apparent ileal digestibility (AID) of nutrients in diets. Data were analyzed using Proc Mixed of SAS. Results: Supplementation of YL (1.5% and 3.0%) replacing poultry fat and blood plasma did not affect growth performance, fecal score and intestinal health. Supplementation of YL at 1.5% did not affect nutrient digestibility, whereas supplementation of YL at 3.0% reduced AID of dry matter (40.2% to 55.0%), gross energy (44.0% to 57.5%), crude protein (52.1% to 66.1%), and ether extract (50.8% to 66.9%) compared to diets without supplementation. Conclusion: Yarrowia lipolytica can be supplemented at 1.5% in nursery diets, replacing 0.8% poultry fat and 0.45% blood plasma without affecting growth performance, intestinal health and nutrient digestibility. Supplementation of YL at 3.0% replacing 1.6% poultry fat and 0.9% blood plasma did not affect growth performance and intestinal health, whereas nutrient digestibility was reduced.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.367-375
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• 2022

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

• Parasites, Hosts and Diseases
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• v.61 no.2
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• pp.138-146
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• 2023

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.33-41
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• 2022

Esculetin (also known as 6, 7-dihydroxycoumarin) a type of coumarin, has been exhibited anti-inflammatory and anti-aging effects. Biorenovation is the microbe-mediated enhancement of biological efficacies and structurally diversified compounds relative to their substrate compounds. The production of different kinds of esculetin derivatives using Bacillus sp. JD3-7 and their effects on lipopolysaccharide (LPS)-triggered inflammatory response in RAW 26.7 cells were assessed. One of the biorenovation products, identified as esculetin 6-O-phosphate (ESP), at concentrations of 1.25, 2.5, and 5 μM inhibited the LPS-stimulated production of inflammation markers of nitric oxide synthase 2 and cyclooxygenase 2 as well as their respective enzymatic reaction products of nitric oxide and prostaglandin E2 in the order of increasing concentrations (1.25, 2.5, and 5 μM). Additionally, ESP treatment suppressed the LPS-stimulated secretion of pro-inflammatory cytokines of interleukin (IL)-1β, IL-6, and tumor necrosis factor- α. Furthermore, these anti-inflammatory effect of ESP was associated with the downregulation of mitogen-activated protein kinase signaling, that is, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase signaling pathways. This study would therefore provide interesting insights into the biorenovation-assisted generation of a novel anti-inflammatory compound. ESP may be used to develop treatments for inflammatory disorders.

• Journal of the Korean Society of Food Culture
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• v.38 no.3
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• pp.176-183
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• 2023

In this study, we investigated the effect of the extracts of Cyrtomium fortunei J.Sm. (CFJ) on lipopolysaccharide (LPS) induced inflammation in mouse BV-2 microglial cells. Nitric oxide (NO) production and cell viability were measured using the Griess reagent and the (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (MTT) assay. Inflammatory cytokines were detected by quantitative polymerase chain reaction (qPCR) in BV-2 microglial cells with and without CFJ extracts. Subsequently, mitogen-activated protein kinases (MAPKs) and antioxidant markers were assessed by western blot analysis. It was found that the CFJ extract significantly decreased the production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-1β) and NO in BV-2 microglial cells that were stimulated with LPS. In addition, the expression levels of the phosphorylation of the MAPK family (p38, c-Jun N-terminal kinases [JNK], and extracellular-signal regulated kinase [ERK]) were reduced by CFJ. Also, treatment with CFJ significantly increased the activities of superoxide dismutase type 1(SOD1) and Catalase in BV-2 microglial cells. Our results indicate that CFJ has a potent suppressive effect on the pro-inflammatory responses of activated BV-2 microglia. Therefore, CFJ has the potential to be an effective treatment for neurodegenerative diseases, as it can inhibit the production of inflammatory mediators in activated BV-2 microglial cells.