• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.317-325
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• 2017

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

• 한국약용작물학회지
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• 제23권2호
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• pp.144-149
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• 2015

The peel of Citrus sunki exhibits multiple biological activities such as anti-oxidant, anti-inflammation and anti-obesity, but little is known about neurodegeneration-related activities. In this study, we investigated the protective effect of ethanolic extract from both immature and mature Citrus sunki peel on neuronal cell death. Treatment of the neuroblastoma cell line SH-SY5Y with $MPP^+$, an inducer of Parkinson disease model, increased cell death in a dose dependent manner. Increased levels of active caspase-3 and cleaved PARP were detected. Treatment with immature Citrus sunki peel extract significantly reduced $MPP^+$-induced neurotoxicity. Cytoprotection with immature Citrus sunki peel extract was associated with a decrease in caspase-3 activation and PARP cleavage. In contrast, mature Citrus sunki peel extract had no significant effects. These data suggest that immature Citrus sunki peel extract may exert anti-apoptotic effect through the inhibition of caspase-3 signaling pathway on $MPP^+$-induced neuronal cell death.

• 동의생리병리학회지
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• 제33권1호
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• pp.31-38
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• 2019

Cheongpyesagan-tang (CP) is one of the traditional medicinal prescription to treat Taeumin (太陰人)'s disease. It has been commonly used for the treatment of stroke, arthritis, diabetes and obesity. In this study, we investigated an anti-inflammatory potential of CP water extract. We examined the effects of CP on the lipopolysarccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). We also examined the levels of protein or mRNA of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and proinflammatory cytokines in RAW 264.7 cells. CP inhibited NO and $PGE_2$ production in a dose dependent manner and decreased the protein and mRNA expression of iNOS and COX-2. Also, CP decreased the mRNA expression of interleukin-6 (IL-6), interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These results suggest that CP has potential as anti-inflammatory therapeutic medicine.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.2146-2152
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• 2015

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

• Journal of Nutrition and Health
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• 제48권5호
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• pp.451-456
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• 2015

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.

• Molecules and Cells
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• 제41권3호
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• pp.244-255
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• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• 대한임상검사과학회지
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• 제50권2호
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• pp.190-196
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• 2018

본 연구는 국민건강영양조사 자료를 이용하여 당뇨병이 없는 성인 4,734명을 대상으로 비만 성인의 hs-CRP와 혈당조절 지표들과의 관련성에 대해 알아보고자 하였다. 연구결과 BMI가 증가할수록 혈당조절지표인 FBG와 fructosamine 및 $HbA_1c$가 증가하였으며, hs-CRP는 비만 군에서 가장 높은 수치를 보였고, 인슐린저항성의 지표인 HOMA-IR도 비만 군에서 통계적으로 유의하게 증가하였다. 또한 hs-CRP 수준을 구분하여 혈당조절지표들과의 관련성을 확인한 결과 hs-CRP가 증가할수록 FBG, fructosamine 및 $HbA_1c$가 증가됨을 확인하였고, 여러 관련 변수를 보정한 후에도 hs-CRP가 증가할수록 FBG, fructosamine 및 $HbA_1c$가 통계적으로 유의하게 증가하였다. 결과적으로 비만과 hs-CRP, 혈당조절지표는 각각에서 연관성을 보여 당뇨병이 없는 성인 중 높은 BMI에서 증가된 hs-CRP에 의해 당뇨병의 주요한 병인인 인슐린 저항성을 증가시켜 혈당조절지표인 FBG, fructosamine 및 $HbA_1c$가 통계적으로 유의하게 증가한 것으로 사료된다. 이에 당뇨병이 없는 성인에서도 올바른 식습관 및 규칙적인 운동으로 비만을 예방하여 당뇨병 발생을 감소시키는 노력이 강구되어야 하겠다.

• 한국식품저장유통학회지
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• 제30권3호
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• pp.502-513
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• 2023

본 연구에서는 영지버섯 균사체 발효 꾸지뽕 잔가지 추출물의 지방세포 분화 억제 및 염증 억제 효과를 확인하고자 하였다. 세포독성을 확인한 결과, 최대 1,000 ㎍/mL 농도까지 세포에 처리하여도 세포 생존율이 감소하지 않음을 확인되었다. 분화과정 동안 발효 꾸지뽕 잔가지 추출물을 처리하였을 때, 세포 내 지방 축적이 감소되었다. 분화과정에 관여하는 대표적인 adipokine인 leptin과 adiponectin의 생성량을 확인한 결과, 발효 꾸지뽕나무 잔가지 추출물에 의해 adiponectin의 생성 증가와 leptin의 생성 감소를 확인하였다. 지방세포 분화 관련 유전자의 발현은 분화 유도인자만 처리한 군에 비해 발효 꾸지뽕나무 잔가지 추출물이 함께 처리된 군에서 추출물의 농도가 높아질수록 지방분화 전사인자인 PPARγ와 C/EBPα의 발현량이 감소하는 것을 확인하였다. 분화된 3T3-L1 세포에서 LPS에 의해 분비되는 염증성 사이토카인(TNF-α, IL-6, MCP-1)의 생성량 변화를 측정한 결과, LPS 처리로 증가된 염증성 사이토카인의 생성을 억제하였으며 염증 관련 유전자인 iNOS, COX-2의 발현도 감소되었다. 또한, 발효 꾸지뽕나무 잔가지 추출물과 발효되지 않은 꾸지뽕나무 잔가지 추출물을 비교하였을 때, 발효 꾸지뽕나무 잔가지 추출물이 지방세포 분화 및 염증 억제 효과에서 더 높은 활성을 보였으며, 이들 결과를 종합적으로 볼 때, 영지버섯 균사체를 이용한 발효가 꾸지뽕나무 잔가지의 활성 증가에 기여하는 것으로 보인다. 따라서 발효 꾸지뽕나무 잔가지 추출물은 항비만, 항염증 소재로서 비만뿐만 아니라 대사성 질환 개선을 위한 기능성 소재로서 활용이 가능할 것으로 판단되며, 향후 발효 꾸지뽕나무 추출물의 명확한 항비만, 항염증 효능을 확인하기 위해서는 유용 물질 분리 및 작용기전 등 추가적인 연구가 필요할 것으로 판단된다.

• 대한본초학회지
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• 제39권3호
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• pp.57-67
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• 2024

Objectives : The aim of this study is to evaluate the potential biological activity of Veronica incana extracts (VIE) through in vitro, ex vivo, and in vivo experiments. Methods : In vitro, we conducted analyses on the total polyphenol (TP) and total flavonoid (TF) levels, alongside DPPHand ABTS radical scavenging activities. Ex vivo evaluations on adipose tissue measured glycerol release as a marker of lipolysis. In LPS-induced RAW 264.7 cells, we quantified nitric oxide (NO) production. Following H₂O₂ induction in U2OS cells, we performed mitochondrial assays such as MitoSox and MitoTracker. Moreover, Bodipy assays were conducted in 3T3-L1 cells. In vivo, we performed anti-osteoarthritis effect of VIE against monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Results : The results presented encompass a myriad of models, from cell culture to animal experiments as well as ex vivo studies. VIE demonstrated high TP and TF contents, potent DPPH and ABTS scavenging activities, and regulated glycerol release. Moreover, the inhibition of NO production in LPS-induced inflammation was notably confirmed and the reduction of lipid droplets was distinctly shown. Furthermore, in H₂O₂-induced U2OS cells, MitoSox was effectively reduced while MitoTracker noticeably increased. In vivo assays confirmed a significant increase in hindpaw weight distribution (HWD) decreased by MIA after VIE treatment. Additionally, VIE inhibited serum inflammatory cytokines (TNF-𝛼, IL-6, and IL-1𝛽) and MDA levels in joint tissue. Conclusion : In conclusion, Veronica incana exhibited various pharmacological effects including antioxidant, anti-obesity, and anti-inflammatory properties.

• Environmental Analysis Health and Toxicology
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• 제28권
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• pp.14.1-14.9
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• 2013

Objectives This study was conducted to determine whether nano-sized carbon black exposure results in greater damage in high fat diet-induced overweight rats than normal weight ones and to identify the possible causes of any differences. Methods Two groups of Sprague-Dawley rats allocated by body weight (normal and overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a day, 5 days per week over a 4-week period. Differential cell counts, lactate dehydrogenase (LDH) activities and albumin concentrations were measured in bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs were evaluated. Tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin (IL)-6 were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated lymphocyte culture. Results Rats exposed to high concentrations of nano-sized carbon black showed significantly increased (p <0.05) polymorphonuclear leukocyte number and LDH activity in the BAL fluid from both overweight and normal rats. Mild histopathological changes were observed in normal rats irrespective of carbon black concentrations. However, severe histological scores were found in overweight rats ($1.75{\pm}0.46$, $2.25{\pm}0.46$, and $2.88{\pm}0.35$ after low, medium, and high concentration exposures). Proinflammatory cytokine levels of TNF-${\alpha}$ and IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes of overweight rats, whereas there was no significant difference in the BAL fluid between normal and overweight rats. Conclusions Inflammation and damage to lungs exposed to nano-sized carbon black was more severe in high fat diet-induced overweight rats compared to normal rats.