• 한국식품과학회지
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• 제30권3호
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• pp.693-696
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• 1998

Chitin의 탈아세틸화로 얻어지는 화합물인 chitosan과 chitooligosaccharide는 다양한 생리활성 기능을 나타내므로 생물의학적인 응용에 많은 관심이 집중되고 있다. 본 연구는 수용성 chitooligosaccharide가 생쥐의 간 기능에 미치는 영향을 조사하기 위하여 수행되었다. 6주 동안 3% cholesterol를 식이한 생쥐에서는 혈장 cholesterol 함량이 증가하였으나, 1% chitooligosaccharide와 3% cholesterol을 함께 식이한 생쥐에서는 혈장 cholesterol 함량이 23% 정도 감소하였다. 그러나 혈장내 HDL-cholesterol과 간내 cholesterol 함량에는 유의한 차이가 없었다. 한편, 15% ethanol을 8주간 투여한 생쥐에서는 inflammation, necrosis, 지방구의 축적, GPT의 활성 증가 등 간 상해가 관찰되었다. 그와 반면에 0.5% chitooligosaccharide와 15% ethanol을 함께 투여한 생쥐에서는 ethanol에 의해 유발된 간 상해가 현저히 억제되어 지방구의 축적이 관찰되지 않았고, 혈장의 GPT 활성이 25%정도 감소하였다. 따라서, chitooligosaccharide가 생쥐에서 혈장 cholesterol 함량을 감소시키고, 알코올성 지방간을 예방하는 등 부분적인 기능이 있음을 보여주었다.

• Molecules and Cells
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• 제46권9호
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• pp.527-534
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• 2023

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.385-394
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• 2020

Eupatilin is known to possess anti-apoptotic, anti-oxidative, and anti-inflammatory properties. We report here that eupatilin has a protective effect on the ethanol-induced injury in rats. Sprague-Dawley rats were divided into 6 groups: control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed to determine the extent of liver damage. Total cholesterol (TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis. Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were quantified to verify the degree of inflammation. Based on our findings, chronic alcohol treatment significantly changed the serum indexes and liver indicators of the model rats, which were significantly improved by eupatilin treatment. Rats in the eupatilin-treatment group showed reduced levels of AST, ALT, TG, TC, TNF-α, and IL-1β, increased SOD activity and GSH levels, and improved overall physiology compared to the alcoholic liver disease model rats. H&E staining also verified the eupatilin-mediated improvement in liver injury. In conclusion, eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatory effects.

• 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.

• International Journal of Internet, Broadcasting and Communication
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• 제12권3호
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• pp.131-138
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• 2020

The cabbage extract of the research does not show cytotoxicity, and thus can be used safely. In an experiment performed on an animal model with liver injury induced by a drug (APAP), it could be seen that the cabbage extract exhibited the effects of protecting liver and improving liver function by effectively reducing AST and ALT which are liver injury markers, indicating that the cabbage extract is effective as a pharmaceutical composition for preventing or treating liver disease. In particular, the cabbage extract was effective in treating inflammation of the liver by reducing the expression of the inflammatory mediators iNOS and COX-2 and the proinflammatory cytokine IL-1β, which are involved in acute inflammatory reactions accompanying liver injury. In the research, an extract of cabbage heat-treated at a temperature of 100 to 150℃ had a better liver function-improving effect or anti-inflammatory effect than an extract of raw cabbage.

• 환경생물
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• 제36권4호
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• pp.498-506
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• 2018

본 연구는 D-galactosamine에 의해 간 손상이 유도된 흰쥐에 다슬기(Semisulcospira libertina) 추출물이 손상된 간세포의 개선 및 회복에 미치는 효과에 관해 조사하였다. 다슬기 추출물은 간 손상에 따른 간 조직 내 국소적 지방 변성과 염증세포 침윤을 크게 감소시켜 대조군과 유사한 수준으로 회복시키는 경향을 나타내었다. 또한 다슬기 추출물은 간 손상 지표 효소인 AST와 ALT, LDH 및 ALP의 증가된 효소 활성을 대조군 수준으로 완화시키며, 간 조직 내 지질과 과산화지질의 함량을 감소시켜 간 손상으로 인한 혈중 효소 활성과 조직 내 지질 함량을 개선하는 것으로 조사되었다. 이와 더불어 다슬기 추출물은 염증반응을 촉진시켜 조직상해 및 괴사를 유도하는 $TNF-{\alpha}$의 발현을 억제시키며, 염증 시 세포를 보호하는 HO-1의 발현을 촉진시켜 염증 반응에서 손상된 세포를 대조군 상태의 세포로 회복시키는데 관여하는 것으로 조사되었다. 따라서 다슬기 추출물은 간조직의 괴사 및 섬유화를 회복시키고 혈액 내 효소의 활성과 조직 내 지질 함량을 개선할 뿐만 아니라 염증 반응 인자의 발현을 조절하고 있어 간 손상으로 인한 간세포의 개선 및 회복에 효과가 높은 기능성 소재로서의 가능성을 제시해 주고있다.

• 대한한방부인과학회지
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• 제34권4호
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

• Nutrition Research and Practice
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• 제6권2호
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• pp.113-119
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• 2012

Guinea pigs were fed a hypercholesterolemic diet (0.25 g/100 g cholesterol) and randomly allocated either to a Control group (n = 9) or to a Lutein (0.1 g/100 g) group (n = 10) for 12 weeks to evaluate oxidative stress and inflammation in both liver and eyes. Malondialdehyde (MDA) concentrations and inflammatory cytokines were measured as well as hepatic nuclear factor-kappaB (NF-${\kappa}B$) binding. Lutein concentrations were greater in eyes ($P$ < 0.01) and liver ($P$ < 0.001) in the Lutein group. All guinea pigs had high concentrations of hepatic cholesterol as well as high plasma ALT and AST levels indicative of liver injury. However, the Lutein group had 43% lower hepatic free cholesterol than the Controls ($P$ < 0.05). Hepatic MDA and MDA in the eye were lower in the Lutein compared to the Control group ($P$ < 0.05). Hepatic tumor necrosis factor-${\alpha}$ was 32% lower in the Lutein group ($P$ < 0.05). Lastly, the Lutein group presented lower NF-${\kappa}B$ DNA binding activity than the Control group ($P$ < 0.001). These results suggest that in the presence of high cholesterol, lutein exerts both antioxidant and anti-inflammatory effects, which can be explained by attenuated NF-${\kappa}B$ DNA binding activity. Furthermore, results also suggest that lutein accumulates in the eyes of guinea pigs to protect against oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1365-1370
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• 2012

The high mobility group box-1 (HMGB1) protein and NALP3 inflammasome have been identified to play important roles in inflammation and cancer pathogenesis, but the relationships between the two and cancer remain unclear. The current study investigated the relationship between HMGB1 and the NALP3 inflammasome in THP-1 macrophages. HMGB1 was found unable to activate the NALP3 inflammasome and failed to induce the release of the IL-$1{\beta}$ and IL-18 in THP-1 macrophages. HMGB1 was also found significantly enhanced the activity of ATP to induce IL-$1{\beta}$ and IL-18 by the induction of increased expression of pro-IL-$1{\beta}$ and pro-IL-18. This process was dependent on activation of RAGE, MAPK p38 and NF-${\kappa}B$ signaling pathway. These results demonstrate that HMGB1 promotes the synthesis of pro-IL-$1{\beta}$ and pro-IL-18 in THP-1 macrophages by the activation of p38 MAPK and NF-${\kappa}B$ through RAGE. HMGB1 likely plays an important role in the first step of the release of the IL-$1{\beta}$ and IL-18, preparing for other cytokines to induce excessive release of IL-$1{\beta}$ and IL-18 which promote inflammation and cancer progression.

• 대한의생명과학회지
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• 제23권2호
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• pp.144-153
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• 2017

It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation ($TNF{\alpha}$ and VCAM-1), fibrosis (${\alpha}-SMA$), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes ($TNF{\alpha}$ and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.