• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.169-175
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• 2016

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) affect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a pro-inflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of inflammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

• 대한의생명과학회지
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• 제24권1호
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• pp.23-29
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• 2018

Abdominal obesity is considered as one of the most risky factors governing the development of metabolic diseases. Here we identify that human chitinase 3-like 1 (CHI3L1, also called YKL-40 in human) single nucleotide polymorphism (SNP), rs883125, is associated with abdominal obesity in Korean women. Korean women subjects with the rs883125 G/G or C/G genotype present higher waist-hip ratio than subjects with C/C genotype suggesting that human subjects who G nucleotide substitution at the rs883125 tended to more accumulate intra-abdominal fat at the abdominal cavity. In addition, Chi3l1 gene expression is increased in adipose tissue from obese mice and pro-inflammatory cytokine enhances Chi3l1 expression in adipocytes, indicating that Chi3l1 is greatly related with obesity and obesity-induced pro-inflammatory responses. Taken together, the minor allele of rs883125 is associated with a higher prevalence of abdominal obesity in Korean women. These findings suggest that genotype of rs883125 can be a biomarker of incident abdominal obesity and abdominal obesity-related metabolic diseases.

• Animal cells and systems
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• 제16권5호
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• pp.385-390
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• 2012

The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and proinflammatory cytokines (TNF-${\alpha}$ and IFN-${\gamma}$) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ caused the elevation of the blood glucose level in D-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the D-glucose-fed group. Our results suggest that the blood glucose level appears to be differentially regulated by various pain stimulation induced by acetic acid, formalin, SP, glutamate, and pro-inflammatory cytokines.

• Biomolecules & Therapeutics
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• 제20권1호
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• pp.118-124
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• 2012

This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of $5{\alpha}$-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted $PGE_2$ production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-${\alpha}$ production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, $5{\alpha}$-reductase inhibition, increase of $PGE_2$ production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale.

• 혜화의학회지
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• 제15권2호
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• pp.121-134
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• 2006

This study saw the anti-allergy effect by the immunity regulation action of Yanghyelyoonbotang (YHYBT) consists 12 kinds of herbal medicine agents. Consequently, YHYBT controlled the amount of secretion of various infla- mmatory cytokines, chemokine, monocyte chemotactic protein and histamine from cells (HMC-1, THP-1, EoL-1) stimulated by PMA, A23187 or HDM. 1. YHYBT did not show cytotoxicity on cultured human fibroblast cells under 250 ${\mu}g/m\ell$ concentration. 2. YHYBT suppressed IL-8, TNF-$\alpha$, IL-6 mRNA expression in the HMC-1 cell stimulated with PMA and A23187. 3. YHYBT significantly suppressed IL-6 release in the THP-1 and EoL-1 cell stimulated with HDM. 4. YHYBT significantly suppressed histamine release in the HMC-1 cell stimulated with PMA and A23187 in a dose-dependent. 5. YHYBT significantly suppressed $\beta$-Hexosaminidase release in the HMC-1 cell stimulated with A23187 in a dose-dependent. 6. YHYBT suppressed NF-$\kappa$B gene expression in the RBL-2H3 cell stimulated with PMA in a dose-dependent. These results suggested that YHYBT has suppressive effects on allergic reaction and pro-inflammatory cytokines in various cell lines through the regulation of immune system. YHYBT has potential to use as an antiallergic agents.

• Journal of Microbiology and Biotechnology
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• 제32권5호
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• pp.638-644
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• 2022

Probiotics modulate the gut microbiota, which in turn regulate immune responses to maintain balanced immune homeostasis in the host. However, it is unclear how probiotic bacteria regulate immune responses. In this study we investigated the immunomodulatory effects of heat-killed probiotics, including Lactiplantibacillus plantarum KC3 (LP3), Lactiplantibacillus plantarum CKDB008 (LP8), and Limosilactobacillus fermentum SRK414 (LF4), via phagocytosis, nitric oxide (NO), and pro-inflammatory cytokine production in macrophages. We thus found that heat-killed LP8 could promote the clearance of foreign pathogens by enhancing the phagocytosis of macrophages. Treatment with heat-killed LP8 induced the production of NO and pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β. In addition, heat-killed LP8 suppressed the production of NO and cytokines in LPS-induced RAW264.7 cells, suggesting that heat-killed LP8 exerts immunomodulatory effects depending on the host condition. In sum, these results indicate that heat-killed LP8 possesses the potential for immune modulation while providing a molecular basis for the development of functional probiotics prepared from inactivated bacterial cells.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1612-1620
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• 2015

양파 껍질 에탄올 추출물(OPEE)의 in vitro 및 in vivo에서 항염증 효과를 알아보기 위해 lipopolysaccharide(LPS)로 활성화된 RAW 264.7 세포로부터 분비되는 염증 관련 매개인자들의 발현량과 ICR 마우스모델을 이용한 귀 부종 및 조직 분석을 진행하였다. NO 및 염증성 cytokine(IL-6, $IL-1{\beta}$ 및 $TNF-{\alpha}$)의 분비량이 OPEE에 의해 농도 의존적으로 감소함을 확인하였다. iNOS 및 COX-2의 발현량은 LPS에 의해 증가하였으나, OPEE 처리에 의해 농도 의존적으로 발현량이 감소하였다. 전사인자인 $NF-{\kappa}B$의 활성과 인산화효소인 MAPKs(p-38, JNK 및 ERK)에서도 LPS에 의해 증가된 발현량이 OPEE에 의해 억제됨을 확인하였다. 따라서 NO 및 염증성 cytokine의 분비량 감소는 $NF-{\kappa}B$와 MAPKs의 활성 저해에 의한 것임을 확인하였다. In vivo 실험에서는 croton oil로 귀 부종을 유발한 마우스에 OPEE를 처리하였을 때 prednisolone 처리구와 유사한 수준으로 귀 부종이 억제되었으며, 귀 조직 관찰에서도 경피 및 진피의 두께와 진피로 침윤된 mast cell의 수도 억제됨을 확인하였다. 이상의 결과 OPEE는 항염증 소재로서 염증을 예방하거나 치료하는 데 이용 가능성이 높음을 제시한다.

• 동의생리병리학회지
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• 제20권4호
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• pp.1044-1050
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• 2006

The Korean genuine medicine, 'Gigukjihwangtanggami (GJT)' has long been used clinically for hypertension and various cerebrovascular diseases. However, experimental study has been carried out very little. Recently cytokines involved in the regulation of inflammatory reactions and immune responses may play an important role in the pathogenesis of cerebral infarction (CI). The aim of this study is to investigate the effect of GJT on the production of pro-inflammatory cytokines and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCS) stimulated with lipopolysaccaride (LPS) from Cl patients. The amount of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interleukin-1{\beta}\;(IL-1{\beta})$, IL-6, IL-8, IL-4 and IL-10 in PBMC culture supernatant was significantly increased in the LPS treated cells compared to unstimulated cells. GJT inhibited the production of $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 induced by LPS. The maximal inhibition rate of the $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 production by pretreatment of GJT (1 mg/ml) was $57.32{\pm}2.5%$ (p.0.05), $42.02{\pm}3.5%$ (p.0.05), $40.02{\pm}2.3%$ (p.0.05) and $48.02{\pm}3.1$, (p.0.05), respectively. In the Other hand, GJT increased the production of IL-4 and IL-10. The maximal increase rate of the IL-4 and IL-10 production by pretreatment of GJT (1 mg/ml) was $42.4{\pm}3.3%$ (p.0.05) End $56.4{\pm}2.9%$ (p.0.05), respectively. Taken together, these results indicate that GJT Ray have regulatory effects on the cytokine production and suggest that GJT might use clinically for the treatment of CI.

• 대한한의학방제학회지
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• 제17권2호
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• pp.151-162
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• 2009

Herba Artemisiae Capillaris is the dried bud of Artemisia capillaris Thunb, which has been used for expelling heat to loosen the bowels and normalizing gallbladder function to cure jaundice in traditional oriental medicines. In the present study, we evaluated the anti-inflammatory effects of the aqueous extracts of Herba Artemisiae Capillaris (HAC) in LPS-activated Raw 264.7 cells. Cells were treated with $1\;{\mu}g/ml$ of LPS 1 h before adding HAC extract. Cell viability was determined by MTT assay, and the relative level of NO was measured with Griess reagent. TNF-$\alpha$, IL-$1{\beta}$, and IL-6 cytokines were detected by ELISA. During the entire experimental period, all three doses of HAC extract (0.03, 0.10 and 0.30 mg/ml) had no significant cytotoxicity. LPS-activated cells showed increased NO levels and iNOS expressions compared to control. However, these increases were dramatically attenuated by treatment with HAC extract. Moreover, the inhibitory effects of HAC extract occurred in a dose-dependent manner. In addition, HAC extract reduced the translocation of $NF{\kappa}B$ into nuclear. HAC reduced production of IL-$1{\beta}$ and IL-6 by LPS, although it had no effects on TNF-$\alpha$. These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of $NF{\kappa}B$ activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Taken together, these results indicate that the aqueous extracts of Herba Artemisiae Capillaris warrant further development as an anti-inflammatory agent for the treatment of gram-negative bacterial infections.