• Journal of Life Science
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• v.33 no.12
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• pp.967-977
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• 2023

Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.

• Molecules and Cells
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• v.47 no.3
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• pp.100033.1-100033.13
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• 2024

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.77-88
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• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

• Journal of Nutrition and Health
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• v.57 no.1
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• pp.27-42
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• 2024

Purpose: This study examined whether regular moderate-intensity treadmill exercise (Ex) and Syzygium aromaticum L. (SA) administration can influence lipid and muscle metabolism in obese rats induced by a 60% high-fat diet (HFD). Methods: Rats, except those in the Normal group, were exposed to a 60% HFD for 4 weeks to induce obesity. The obese rats were assigned randomly to three groups: HFD control group, HFD+Ex group, and HFD+Ex+SA group. Treadmill exercise was conducted five times a week for 4 weeks, with a 5° incline and a speed of 18 m/min (Week 1: 20 minutes; Weeks 2: 25 minutes; Weeks 3-4: 30 minutes). Serum analysis was performed. Western blot analysis was conducted on the liver and soleus muscle, and histopathological analysis was carried out on the liver and adipose tissues. Results: The body weight change in the Ex groups was significantly lower than in the HFD control group, while the soleus muscle weight in the HFD+Ex group increased significantly. The histopathological examination in the Ex groups revealed a marked reduction in liver lipid accumulation and a decrease in adipocyte size in adipose tissue. Obesity induction increased leptin levels substantially, but Ex notably reversed these changes. Ex resulted in significant inhibition of ROS and ONOO^-, whereas the serum inflammatory cytokine, IL-1β, and total cholesterol were reduced only by SA administration. Furthermore, the inflammatory proteins in the liver were inhibited more effectively when Ex was supplemented with SA. The expression of the muscle synthesis-related proteins and degradation proteins were modulated by Ex and Ex+SA. Conclusion: Ex significantly affected lipid and muscle metabolism, and adding SA alleviated the inflammation.

• Polymer(Korea)
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• v.32 no.2
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• pp.109-115
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• 2008

Because demineralized bone particle (DBP) contains various bioactive molecules such as cytokines, it is widely used biomaterials in the field of tissue engineering. In this study, we investigated the effect of 2-dimensional DBP/PLGA hybrid films on adhesion, proliferation and phenotype maintenance of intervertebral disc cells. PLGA films incorporated with different amount (0, 10, 20, 40 and 80 wt%) of DBP were prepared by the solvent evaporation method and characterized by scanning election microscopy (SEM). PLGA film has a flat and smooth surface. According to the increase of content of DBP, the surface of DBP/PLGA film exhibited few agglomerates and increased the roughness of the surface. Annulus fibrosus (AF) and nucleus pulposus (NP) cells were cultured on PLGA and DBP/PLGA film surface, and then examined the cell adhesion and proliferation by the cell count and SEM observation. The result of cell count and SEM observation revealed that 10 and 20% DBP in DBP/PLGA films were superior to adhesion and proliferation of both AF and NP cells. We confirmed that specific gene expression of disc cells on DBP/PLGA film based on the cell count result. Disc cells seeded on 20% DBP/PLGA film expressed the gene of type I and II collagen continuously. Therefore, pertinent content of biomaterials could provide more appropriate condition on adhesion and proliferation of cell. And this results may be used as a basic data for the intervertebral disc regeneration using tissue engineering.

• Journal of Life Science
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• v.28 no.2
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• pp.141-147
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• 2018

This study aimed to analyze the contents of rutin, procyanidin B3, quercetin, and kaempferol, known to have antioxidant, anti-inflammatory, and anti-carcinogenic effects, among the polyphenol types contained in grape pruning stem extracts (GPSE). It utilized grape stems discarded after harvest to measure the effects of GPSE on skin moisture, inhibition of skin cell proliferation, and anti-inflammatory activity on the damaged skin of HR-1 mice induced with ultraviolet B (UVB), and to verify the applicability of GPSE as a material for functional food and functional cosmetics. The polyphenol was extracted from grape pruning stems with 80% EtOH, and then the extract was used while storing at $-20^{\circ}C$, after filtering, concentrating, and freeze-drying it. The content of an active ingredient of GPSE was analyzed using high performance liquid chromatography (HPLC). From 53 kg of the grape pruning stem specimen, 2.34 kg of the EtOH fraction extracts were extracted to achieve a 4.42% yield ratio. Analysis of the active ingredients showed 0.28 mg/g of procyanidin B3, 12.81 mg/g of rutin, 0.51 mg/g of quercetin, and 8.24 mg/g of kaempferol. After UVB irradiation on the dermis, to confirm the degree of inhibition of collagen synthesis, we examined the protein expression of MMP-9 using immunohistochemical staining. The results of this study confirm the existence of active polyphenol types, such as rutin, kaempferol, quercetin, and procyanidin B3, in GPSE. Moreover, the study found that GPSE has anti-collagenase effects and it decreases the effects of UV damage on skin barrier function. GPSE is a functional ingredient with a potential for skin protection effects, and it has high utilization potential as an ingredient for functional cosmetics.

• Journal of Life Science
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• v.25 no.10
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• pp.1081-1090
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• 2015

Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferator-activated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.5
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• pp.761-767
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• 2007

This study was conducted to determine the effects of exogenous zinc-metallothionein (Zn-MT) on anti-oxidative function and pork quality. After feeding a corn-soybean meal-based diet for two weeks, 48 pigs ($Duroc{\times}Landrace{\times}Chinese\;Black Pig$) were assigned randomly to four groups. Pigs in Group 1 were maintained under non-stress conditions, whereas pigs in Groups 2, 3 and 4 were aggressively handled for 25 min to produce stress. Pigs in Groups 1, 2, 3, and 4 received intramuscular administration of saline (control group; CON), 0 (negative control group; NCON), 0.8 (low dose group; LOW), and 1.6 (high dose group; HIGH) mg rabbit liver Zn-MT per kg body weight, respectively. Pigs were slaughtered at 3 and 6 h post-injection. Zn-MT treatment increased (p<0.05) the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) while decreasing the concentration of malondialdehyde (MDA) in liver. These responses were greater (p<0.05) at 6 h than at 3 h post Zn-MT injection. Zn-MT treatment increased (p<0.05) hepatic SOD mRNA levels in a time and dose-dependent manner and decreased (p<0.05) serum glutamate-pyruvate transaminase and lactate dehydrogenase activities (indicators of tissue integrity). Zn-MT administration decreased (p<0.05) lactate concentration and increased (p<0.05) pH and water-holding capacity in the longissimus thorasis meat. Collectively, our results indicate that intramuscular administration of Zn-MT to pre-slaughter stressed pigs improved tissue anti-oxidative ability and meat quality.

• Journal of Life Science
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• v.30 no.2
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• pp.113-121
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• 2020

Macrophages are initiators for regulating a host's defenses to eliminate pathogens and trigger tissue repair. Macrophages are classified into two types: classically (M1) activated macrophages and alternatively (M2) activated macrophages. M1-phenotype macrophages directly or indirectly kill infectious organisms and tumor cells via pro-inflammatory responses, whereas M2-phenotype macrophages remodel wounded tissue through anti-inflammatory responses. In this paper, we investigated how Phellinus linteus hot water extract passed from Diaion HP-20 resin (PLEP) regulates polarization of M1-like or M2-like macrophages in human THP-1 cells. PLEP did not have cytotoxicity at a high concentration of 300 ㎍/ml. We observed morphological alteration of the THP-1 cells, which are stimulated by PLEP, LPS/INF-γ (M1 stimulators) or IL-4/IL13 (M2 stimulators). PLEP exposure induced morphology contiguous with LPS/INF-γ. qPCR was also performed to determine whether PLEP influences M1 or M2 polarization-related genes. M1-phenotype macrophage-specific genes, such as TNF-α, IL-1β, IL-6, IL-8, CXCL10 and CCR7, were enhanced by PLEP in a dose-dependent manner similar to LPS/INF-γ. Conversely, M2-phenotype-specific genes, such as MRC-1, DC-SIGN, CCL17 and CCL22, were suppressed by PLEP. PLEP also significantly up-regulated secretory inflammation cytokines related to M1 polarization of macrophages, including TNFα, IL-1β and IL-6, which was similar to the gene expression. Further, MAPK and NF-κB signaling were increased by treatment with PLEP, resulting in enhancement of cytokine secretion. PLEP might therefore be used as a promising booster of pro-inflammatory responses through M1 polarization of human THP-1 cells.