• 한방안이비인후피부과학회지
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• 제33권3호
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• pp.99-114
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• 2020

Objectives : To investigate treatment approaches of psoriasis, and to provide universal and holistic standards to assist in optimizing patient care and future research. Methods : Review articles of psoriasis regarding pathophysiology, risk factor or treatment were searched from Pubmed (January 2016 to June 2020). Treatment approaches were investigated based on the searched articles. Additional data collecting was done for further discussion by searching Pubmed and Google scholar with keywords relevant to the approaches, and the relevant references of articles retrieved were manually inspected to be included. Results : Modalities to directly regulate the relevant helper T cell or inflammatory cytokines can constitute the treatment approaches of psoriasis. Modalities to treat gastrointestinal tract inflammation, to correct metabolic syndrome and to improve epidermal lipid abnormality via whole body lipid metabolism can also constitute the treatment approaches of psoriasis. Probable adverse effects of long term use of western medication should be addressed carefully, and alleviating the hazards of western medication can be a treatment approach of psoriasis. Conclusion : Treatment of psoriasis should take account of systemic aspects such as gastrointestinal tract and lipid metabolism. Treatment approaches of psoriasis established on the pathophysiological basis can serve as universal standards.

• Journal of Ginseng Research
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• 제48권1호
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• pp.89-97
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• 2024

Background: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). Methods: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRα^-/- mice. Results: Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRα^-/- mice. Conclusion: GF2 alters the binding affinities of LXRα coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD.

• Molecules and Cells
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• 제43권11호
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• pp.964-973
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• 2020

Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the proinflammatory status of immune cells. Thiamine, a wellknown co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

• 한국응용과학기술학회지
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• 제36권4호
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• pp.1164-1171
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• 2019

Dietary supplements derived from natural sources are an essential factor in optimizing athletic performance. It has been proposed that the extract of Momordica charantia (M. charantia) that is known as a bitter melon can be potentially used as a novel supplement for health promotion. This pilot study aimed to examine the effects of the M. charantia extract when administered in the form of a sports drink, and we evaluated changes in body composition and metabolic factors in tennis players after 4-week consumption of the extract. Eight male college tennis players were instructed to consume an M. charantia extract 6 times per day (3 in the morning and 3 in the afternoon, and the total daily intake was 600 ml). Collected data were analyzed using paired t-tests to examine the changes over time after consumption of the M. charantia extract. The results revealed a significant increase in the trunk muscle mass, basal metabolic rate, and daily calorie intake (p < 0.05). Levels of protein, minerals, and total body water showed an increased tendency (not statistically significant), whereas intracellular water and extracellular water showed a decreased trend. Furthermore, fat-free mass, skeletal muscle mass, and muscle mass showed an increased tendency. In conclusion, consumption of the M. charantia extract caused an increase in parameters related to protein, muscle mass, and metabolism. It seems that follow-up studies related to fatigue, inflammation, and stress hormones related to the M. charantia extract consumption would be needed.

• Clinical Nutrition Research
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• 제6권3호
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• pp.172-182
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• 2017

We investigated the association between dietary habits/food group consumption patterns and early risk of metabolic syndrome (MetS), a main cause for metabolic disease. Study participants were recruited from the health promotion center in Dong-A University Hospital and public advertisement. Study subjects (n = 243, 21-80 years) were categorized into three groups: Super-healthy (MetS risk factor [MetS RF] = 0, n = 111), MetS-risk carriers (MetS RF = 1-2, n = 96), and MetS (MetS $RF{\geq}3$, n = 27). Higher regularity in dietary habits (breakfast-everyday, regular eating time, non-frequent overeating, and non-frequent eating-out) was observed in the Super-healthy group than in the MetS-risk carriers, and particularly in the MetS subjects. The relationship between food group consumption patterns and MetS-risk related parameters were investigated with adjustment for confounding factors. Fruit consumption was positively associated with HDL-cholesterol, and tended to be negatively associated with waist circumference, triglyceride, LDL-cholesterol, and insulin resistance (IR). The consumption of low-fat meats and fish, and vegetables was negatively associated with hs-CRP. Specifically, the consumption of seafoods belonging to the low-fat fish was negatively associated with fasting glucose, hs-CRP, and interleukin (IL)-6. Anchovy/dried white baits consumption was negatively associated with fasting insulin and IR. Green-yellow vegetables consumption was negatively associated with fasting insulin, IR, and hs-CRP. On the other hand, sugars and fast-foods were positively associated with LDL-cholesterol. Additionally, fast-foods consumption was positively associated with hs-CRP and IL-6 levels. In conclusion, dietary habits/food group consumption patterns are closely associated with MetS-risk related parameters in Koreans. It may suggest useful information to educate people to properly select healthy foods for early prevention of MetS.

• Journal of Periodontal and Implant Science
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• 제49권2호
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• pp.105-113
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• 2019

Purpose: An unresolved inflammatory state contributes to the pathogenesis of periodontal disease and metabolic syndrome (MetS). Therefore, the purpose of this study was to evaluate the role of lipoxin A4 (LXA4), a proresolving lipid mediator, in the association between periodontal disease and MetS. Methods: Sixty-seven patients with MetS and 65 patients without MetS were included in the study. Sociodemographic information was obtained via a questionnaire, and detailed medical diagnoses were made. Periodontal parameters (plaque index [PI], gingival index [GI], probing pocket depth [PD], and clinical attachment level [CAL]) and metabolic parameters were measured, and serum LXA4 levels were determined. The associations among MetS, periodontal parameters, and serum LX levels were evaluated by adjusted multivariate linear regression analyses. Results: Patients with MetS were older and had a higher body mass index than patients without MetS. Periodontal parameters (PI, GI, PD, and CAL) were higher in patients with MetS than in those without MetS. Serum LXA4 levels were higher in patients without MetS. Multivariate linear regression analysis indicated a positive association between MetS and periodontal parameters (PD and CAL). Negative associations were established between MetS and LXA4 levels, and between LXA4 and periodontal parameters (PI, PD, and CAL). Conclusions: The presence of higher values of periodontal parameters in patients with MetS and the negative relationship of LXA4 with MetS and periodontal disease may support the protective role of proresolving lipid mediators in the association between periodontal disease and MetS.

• Journal of Ginseng Research
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• 제48권1호
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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.

• Nutrition Research and Practice
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• 제10권6호
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• 한국식품과학회지
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• 제53권5호
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• pp.561-569
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• 2021

본 연구를 통하여 블랙커런트 추출물의 섭취가 제 2형 당뇨동물 모델인 db/db 마우스에서 혈당 개선 및 사구체 확장, 신장 섬유증, 염증을 억제하여 당뇨병성 신병증을 개선했다는 것을 입증했다. 제 2형 당뇨병 db/db 마우스에서 블랙커런트 추출물의 섭취가 인슐린 저항성 및 신장 기능 장애와 같은 당뇨병 관련 대사 장애를 개선하고, 당뇨병성 신병증에 있어 신장 염증 및 신장 섬유증을 현저하게 약화시켰다는 것을 보여주었다. 결론적으로, 이러한 연구 결과는 블랙커런트 추출물이 신장 섬유증, 염증 및 이에 따른 당뇨병성 신병증의 예방에 중요한 역할을 할 수 있다는 증거를 제공한다. 따라서 당뇨병 관련 신기능 장애에 대한 블랙커런트 추출물의 보호 역할은 당뇨병성 신병증 개선 건강성 식품 개발에 대한 새로운 통찰력을 제공 할 수 있다.