일부 여자대학생의 비만관련 인자 및 염증반응지표와 비만 호르몬과의 관계

최혜진,조정호,신말연,이지현,최보인,김희정,김선민,정재현,정상선,양명주,이종도 대한임상건강증진학회 2009 Korean Journal of Health Promotion Vol.9 No.2

Background : Leptin is a protein hormone produced primarily by fat cells and plays a key role in regulating energy intake and expenditure including appetite and metabolism. But whether leptin is associated with obesity-linked factors and inflammatory factors across gender is not clear. We investigated the relationships between leptin and obesity-linked factors (weight, percent body fat, waist-hip-ratio, body mass index, blood pressure, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride) and inflammatory factors (interleukin-6, C-reactive protein, tumor necrosis factor-α, and white blood cell) in 31 female college students. Methods : We measured total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), interleukin--6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), white blood cell (WBC), and leptin hormone level using an enzymatic method. Percent body fat, fat mass, weight, height, waist-hip ratio (WHR), and body mass index (BMI) were analyzed using bioelectrical impedance (Biospace Co.), and blood pressure was measured by auto blood pressure machine (MD 730, Korea). Pearson product-moment correlation was used to investigate correlations between leptin and obesity-linked factors and inflammatory factors. Multiple linear regression was used to examine the associations between leptin and obesity-linked factors and inflammatory factors. Results : Leptin was significantly associated with weight (r=0.59, p=0.00), percent body fat (r=0.80, p=0.00), WHR (r=0.81, p=0.00), BMI (r=0.67, p=0.00), LDL-C (r=0.43, p=0.02), and CRP (r=0.40, p=0.03). In multiple linear regression analysis, percent body fat (t=6.39) and HDL-C (t=2.18) were shown to be significant predictors of the body's level of leptin. Percent body fat and HDL-C account for a variance in leptin levels of 76% in young female college students. Conclusions : We concluded that in order to properly adjust the level of leptin in female college students, a most effective strategy is to reduce percent body fat, WHR, BMI, LDL-C, TG, and CRP. 연구배경 : 본 연구는 여자대학생들의 비만관련 인자, 염증반응지표, 그리고 렙틴 호르몬을 측정하여 관련성을 비교 분석함으로써 여자대학생의 건강증진을 위한 기초자료를 제공하는데 연구의 목적이 있다. 방 법 : 연구 대상자는 여자대학생을 무선표집으로 31명을 추출하였다. 혈액을 채취를 통하여 총콜레스테롤, 고밀도 지단백 콜레스테롤, 저밀도 지단백 콜레스테롤, C-반응단백, 인터루킨-6, 종양괴사인자-알파, 백혈구, 렙틴 호르몬을 분석하였고, 생체전기저항법으로 체지방률, 체지방량, 신장, 체중, 허리엉덩이둘레비율, 신체질량지수를 측정하였으며, 자동전자혈압계 (MD 730, Korea)를 이용하여 혈압을 측정하였다. 모든 자료의 통계처리는 렙틴 호르몬과 비만관련 인자, 염증반응지표와의 관련성을 피어슨 상관분석과 다중선형회귀분석, Dubin Watson Test를 통하여 분석하였다. 결 과 : 여자대학생의 렙틴 호르몬은 체중, 체지방률, 허리엉덩이둘레비율, 신체질량지수, 저밀도 지단백 콜레스테롤, 중성지방, C-반응단백과 유의한 상관관계가 있는 것으로 나타났다(p<.05). 그리고 체지방률, 고밀도 지단백 콜레스테롤은 렙틴 호르몬의 독립적인 예측인자로 나타났고(p<.05), 회귀식의 설명력은 76%로 나타났다. 결 론 : 렙틴 호르몬을 적절하게 조절하기 위해서는 체지방률, 허리엉덩이둘레비율, 신체질량지수, 저밀도 지단백 콜레스테롤, 중성지방, C-반응단백을 줄이는 것이 가장 효과적인 전략이라고 볼 수 있다.

쥐와 개의 척수 손상 모델에서 신경영양인자의 변화 및 의미

송인수,양준영,이준규,주용범,차수민 대한척추외과학회 2011 대한척추외과학회지 Vol.18 No.1

Study Design : Experimental, prospective study Objectives : To examine the changes in the variable factors after an acute spinal cord injury(SCI) in rats and dogs simultaneously. Summary of Literature Review : No study has examined the variations of several factors in a SCI model in different species. Materials and Methods : In rats, a laminectomy was performed at the T10 level and the injured spinal cord was extracted. In Beagle dogs, the laminectomy level was T10 and T11. The motor function was evaluated using a modified Tarlov’s scale. A RT2 profiler PCR array was used to examine each factor (inflammatory cytokines, factors-related with apoptosis, neurotrophic factors, factors-related with extraceullar matrix). Results : IL-2, TNF, TNFRSF11B increased with time and showed no statistical difference between two species, but TNFSF13B showed a significant difference. BDNF decreased with time in both species, and GDNF was significantly lower in dogs. NGFβ, CTNF and its receptors showed no significant changes in the two species. MMP1 increased in both species but MMP7 decreased in rats and increased in dogs with time, and showed a significant difference between species. Conclusion : The change in inflammatory cytokines and extracellular matrix correlates with each factor in the combined patterns. Moreover, during the first week after SCI, inflammatory cytokines, apoptosis, neutrophic factors, and extracellular matrix factors may show a partial difference between experimental animals, which means that an animal model can be selected according to the particular experimental plan. Key Words : Spinal cord injury, Inflammatory cytokines, Factors-related with apoptosis, Neurotrophic factors, Factors-related with extraceullar matrix 연구방법: 실험적, 전향적 연구목적: 급성 척수 손상 후 다양한 인자의 변화가 쥐와 개에서 어떻게 일어나는 지 동시에 알아보고자 하였다. 선행문헌의 요약: 다른 종(種)간의 급성 척수 손상 후 다양한 신경 인자(염증 사이토카인, 세포 사멸과 연관된 인자, 신경영양인자, 세포외 기질과 연관된인자) 들의 변화를 비교하는 연구는 지금까지 없었다. 대상 및 방법: 쥐의 10번째 흉추 위치에서 추궁 절제를 시행 후, 인위적 척수 손상을 유발하였고 개에서는 10번째와 11번째 흉추에서 추궁 절제, 척수손상을 유발하였다. 운동학적 평가는 변형된 Tarlov’s scale을 이용하였다. 염증 사이토카인(IL-2, TNF, TNFRSF11B, TNFSF13B), 세포 사멸과 연관된인자(JUN, NFKβ1), 신경영양인자(BDNF, GDNF, NGFβ, NGFRAP1, CNTF, CNTFR), 세포외 기질과 연관된 인자(CSPG2, MMP1, MMP7) 분석에 RT2profiler PCR array를 이용하였다. 결과: IL-2, TNF, TNFRSF11B는 시간이 경과함에 따라 증가하였고 두 종간에 통계학적 차이는 없었으나 TNFSF13B는 통계학적으로 의미 있는 차이를보였다. BDNF는 두 종 모두 시간이 경과하면서 감소하였고 GDNF는 개에서는 확연히 감소하였고 이는 통계적으로 의미 있는 차이를 보였다. NGFβ,CNTF와 그 수용체들은 종간의 뚜렷한 차이는 관찰되지 않았다. MMP1은 두 종 모두에서 증가하였으나 MMP7은 쥐에서는 시간이 경과할수록 감소하고 개에서는 증가하는 양상을 보였으며, 두 종간에 의미 있는 차이를 나타내었다. 결론: 신경영양인자를 중심으로 염증 사이토카인과 세포외 기질 인자의 변화는 상호 작용하는 것이며, 척수 손상 후 급성기 중 일주일까지 염증, 세포사멸, 신경영양인자, 그리고 세포외 기질의 연구에 실험 동물간에 일부 차이가 있음을 알 수 있어 향후 실험 계획 중 동물 모델의 선정 자료로 활용할 수있을 것이다. 색인 단어: 척수 손상, 염증 사이토카인, 세포 사멸 인자, 신경영양인자, 세포외 기질 인자약칭 제목: 척수 손상 후의 신경인자들의 변화

10주간의 복합운동이 비만 중년여성의 대사증후군 관련인자 및 염증인자에 미치는 영향

오수일,황예선,유민주 대한운동학회 2014 아시아 운동학 학술지 Vol.16 No.3

[PURPOSE] The purpose of the present study was to investigate the effect of combined exercise program on obese middle-aged women's metabolic syndrome related factors and inflammatory factors[WBC(White Blood Cell), GGT(γ-glutamyl Transferase), UA(Uric Acid)] for 10 weeks. [METHOD] The subjects were consisted of a metabolic syndrome group(23 persons) and a normal group(17 persons) according to the status of metabolic syndrome among 40 middle-aged women who were currently obese or on the boundary of obesity. The exercise program consisted of aerobic exercise using stationary bikes and resistance exercise including sit-ups, leg lifting, push-ups, sitting down and up, lifting the heel, etc for 10 weeks, 3 times a week, 70 minutes (warm-up; 5 minutes, main exercise; 60 minutes, cool-down; 5 minutes). [RESULT] According to the results of metabolic syndrome related factors, significant difference between groups was shown in all items (Glucose, W/H, blood pressure, TG, HDL-C). And with regard to difference between periods, significant difference in systolic blood pressure and HDL-C was shown. In case of inflammatory factors, significant difference between groups was shown in WBC, GGT, and UA. The correlation and regression results of metabolic syndrome related factors and inflammatory factors showed that Glucose and TG had positive correlation with WBC in metabolic syndrome group, and had influence of 12% and 20.4% respectively. [CONCLUSION] Owing to the combined exercise performed for 10 weeks, positive results were shown in systolic blood pressure and HDL-C among metabolic syndrome related factors, but it was impossible to find meaningful results in inflammatory factors. However, all of WBC, GGT, and UA showed a decreasing trend. Accordingly, it is thought that a positive effect can be expected if exercise is performed for a long time.. [목적] 본 연구는 10주간의 복합운동 프로그램이 비만 중년 여성의 대사증후군 관련인자 및 염증인자에 어떠한 영향을 미치는지 알아보았다. [방법] 연구 대상자는 현재 비만이거나 비만 경계에 있는 중년여성 40명 중 대사증후군 유·무에 따라 대사증후군 집단(23명)과 정상 집단(17명)으로 구성하였다. 운동 프로그램은 고정식 바이크를 이용한 유산소운동과 윗몸일으키기, 다리들어올리기, 팔굽혀펴기, 앉았다 일어나기, 발뒤꿈치 들기 등을 적용한 저항운동을 본 운동으로 하여 10주간, 주 3회, 70분(준비운동; 5분, 본운동; 60분, 정리운동;5분) 실시하였다. [결과] 대사증후군 관련인자 결과, 대사증후군 집단과 정상집단 간 모든 항목(Glucose, W/H, 혈압, TG, HDL-C)에서 유의한 차이가 나타났으며, 시기 간 차이에서는 수축기혈압과 HDL-C의 유의한 차이가 나타났다. 염증인자에서는 WBC, GGT, UA 항목 모두에서 집단 간 유의한 차이가 나타났다. 대사증후군 관련인자와 염증인자의 상관과 회귀 결과에서는 대사증후군 집단에서 Glucose와 WBC, TG와 WBC에서 정적인 상관을 보였으며, 각12%와 20.4%의 영향력을 나타냈다. [결론] 10주간의 복합운동 실시로 대사증후군 관련인자 중 수축기 혈압과 HDL-C에는 긍정적인 결과를 나타냈으나 염증인자에서는 의미 있는 결과를 볼 수 없었다. 하지만, WBC, GGT, UA 모두 감소 경향을 나타내 장기간 운동의 실시로 긍정적인 효과를 기대할 수 있을 것으로 생각된다.

TNF-α로 유도된 HaCaT 각질형성세포의 염증반응에서 해죽순의 항염증 효과

배기상 ( Gi-sang Bae ),박성주 ( Sung-joo Park ) 대한본초학회 2019 大韓本草學會誌 Vol.34 No.1

Objectives : Nypa fruticans Wurmb. (NF) have been used as a traditional medicine to treat inflammatory diseases in East-South Asia. However, it is largely undiscovered whether NF water extract could exhibit anti-inflammatory activities against tumor necrosis factor-α (TNF-α)-induced inflammatory responses on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the anti-inflammatory activity of NF water extract on TNF-α-induced inflammatory responses in HaCaT cells. Methods : To investigate the anti-inflammatory activites of NF water extract in HaCaT cells, the inflammatory model of HaCaT cells was established under a suitable concentration (10 ng/ml) of human TNF-α (hTNF-α). HaCaT keratinocyte cells were pre-treated with NF water extract for 1 h, and then stimulated with hTNF-α. Then, the cells were harvested to measure the inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin E₂ (PGE₂), and pro-inflammatory cytokine including TNF-α and interleukin (IL)-6. In addition, we examined the inhibitory mechanisms of NF, mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha (Iκ-Bα) Results : The treatment of NF inhibited the hTNF-α-induced elevation of iNOS, COX-2, and PGE₂ in HaCaT cells. In addition, NF treatment inhibited the hTNF-α-induced elevation of TNF-α and IL-6. Furthermore, NF treatment inhibited the activation of MAPKs but not degradation of Iκ-Bα. Conclusions : Taken together, our result suggest that treatment of NF could inhibit the hTNF-α-induced inflammatory responses via deactivation of MAPKs in HaCaT cells. This study could suggest that NF could be a beneficial agent to prevent skin damage or inflammation.

Anti-Inflammatory Effects of Hexane Fraction from White Rose Flower Extracts via Inhibition of Inflammatory Repertoires

( Hwa Jeong Lee ),( Han Seok Kim ),( Seung Tae Kim ),( Dong Sun Park ),( Jin Tae Hong ),( Yun Bae Kim ),( Seong Soo Joo ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.3

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-1β, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-κB (NF-κB) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-κB and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

AKT-targeted anti-inflammatory activity of Panax ginseng calyx ethanolic extract

Sang Yun Han,김주원,Eunji Kim 고려인삼학회 2018 Journal of Ginseng Research Vol.42 No.4

Background Korean ginseng (Panax ginseng) plays an anti-inflammatory role in a variety of inflammatory diseases such as gastritis, hepatitis, and colitis. However, inflammation-regulatory activity of the calyx of the P. ginseng berry has not been thoroughly evaluated. To understand whether the calyx portion of the P. ginseng berry is able to ameliorate inflammatory processes, an ethanolic extract of P. ginseng berry calyx (Pg-C-EE) was prepared, and lipopolysaccharide-activated macrophages and HEK293 cells transfected with inflammation-regulatory proteins were used to test the anti-inflammatory action of Pg-C-EE. Methods The ginsenoside contents of Pg-C-EE were analyzed by HPLC. Suppressive activity of Pg-C-EE on NO production, inflammatory gene expression, transcriptional activation, and inflammation signaling events were examined using the Griess assay, reverse transcription-polymerization chain reaction, luciferase activity reporter gene assay, and immunoblotting analysis. Results Pg-C-EE reduced NO production and diminished mRNA expression of inflammatory genes such as cyclooxygenase-2, inducible NO synthase, and tumor necrosis factor-α in a dose-dependent manner. This extract suppressed luciferase activity induced only by nuclear factor-κB. Interestingly, immunoblotting analysis results demonstrated that Pg-C-EE reduced the activities of protein kinase B (AKT)1 and AKT2. Conclusion These results suggest that Pg-C-EE may have nuclear-factor-κB-targeted anti-inflammatory properties through suppression of AKT. The calyx of the P. ginseng berry is an underused part of the ginseng plant, and development of calyx-derived extracts may be useful for treatment of inflammatory diseases.

AKT-targeted anti-inflammatory activity of Panax ginseng calyx ethanolic extract

Han, Sang Yun,Kim, Juewon,Kim, Eunji,Kim, Su Hwan,Seo, Dae Bang,Kim, Jong-Hoon,Shin, Song Seok,Cho, Jae Youl The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.4

Background: Korean ginseng (Panax ginseng) plays an anti-inflammatory role in a variety of inflammatory diseases such as gastritis, hepatitis, and colitis. However, inflammation-regulatory activity of the calyx of the P. ginseng berry has not been thoroughly evaluated. To understand whether the calyx portion of the P. ginseng berry is able to ameliorate inflammatory processes, an ethanolic extract of P. ginseng berry calyx (Pg-C-EE) was prepared, and lipopolysaccharide-activated macrophages and HEK293 cells transfected with inflammation-regulatory proteins were used to test the anti-inflammatory action of Pg-C-EE. Methods: The ginsenoside contents of Pg-C-EE were analyzed by HPLC. Suppressive activity of Pg-C-EE on NO production, inflammatory gene expression, transcriptional activation, and inflammation signaling events were examined using the Griess assay, reverse transcription-polymerization chain reaction, luciferase activity reporter gene assay, and immunoblotting analysis. Results: Pg-C-EE reduced NO production and diminished mRNA expression of inflammatory genes such as cyclooxygenase-2, inducible NO synthase, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. This extract suppressed luciferase activity induced only by nuclear factor-${\kappa}B$. Interestingly, immunoblotting analysis results demonstrated that Pg-C-EE reduced the activities of protein kinase B (AKT)1 and AKT2. Conclusion: These results suggest that Pg-C-EE may have nuclear-factor-${\kappa}B$-targeted anti-inflammatory properties through suppression of AKT. The calyx of the P. ginseng berry is an underused part of the ginseng plant, and development of calyx-derived extracts may be useful for treatment of inflammatory diseases.

Inhibition of Nuclear Factor κB Activation and Cyclooxygenase-2 Expression by Aqueous Extracts of Hispanic Medicinal Herbs

Robert A. Orlando,Amanda M.,Lucy A. Hunsaker,Carolina R.,Robert E. Royer,David L. Vander Jagt,Dorothy J. Vander Jagt 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.4

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a primary choice of therapy for diseases with a chronic inflammatory component. Unfortunately, long-term NSAID therapy is often accompanied by severe side effects, including cardiovascular and gastrointestinal complications. Because of this, there is critical need for identification of new and safer treatments for chronic inflammation to circumvent these side effects. Inflammatory diseases have been successfully remedied with natural herbs by many cultures. To better understand the potential of natural herbs in treating chronic inflammation and to identify their mechanism of action, we have evaluated the anti-inflammatory activities of 20 medicinal herbs commonly used in the Hispanic culture. We have established a standardized method for preparing aqueous extracts (teas) from the selected medicinal herbs and screened for inhibition of tumor necrosis factor-α-induced activation of nuclear factor κB (NF-κB), which is the central signaling pathway of the inflammatory response. A number of herbal teas were identified that exhibited significant anti-inflammatory activity. In particular, tea from the herb commonly called laurel was found to be an especially potent inhibitor of NF-κB-dependent cyclooxygenase-2 gene expression and prostaglandin E2 production in cultured murine macrophages. These findings indicate that laurel tea extract contains potent anti-inflammatory compounds that function by inhibiting the major signal transduction pathway responsible for inducing an inflammatory event. Based on these results, laurel may represent a new, safe therapeutic agent for managing chronic inflammation.

Regulatory Effect of Inflammatory Cytokines Secretion and Hypoxia-inducible $Factor-1{\alpha}$ Activation by Panax ginseng

조철원,이승희,김동웅,이성균,송봉근,Zo, Chul-Won,Lee, Seung-Hee,Kim, Dong-Woung,Lee, Seong-Kyun,Song, Bong-Keun The Society of Internal Korean Medicine 2006 大韓韓方內科學會誌 Vol.27 No.4

목적 : 인삼은 다양한 생물학적 작용이 있다. 그 중 항염증작용과 관련하여 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과를 살펴보고자 한다. 방법 : phorbol myristate acetate (PMA)+A23187에 유도된 세포에서 염증성 cytokines 분비의 변화와 인간의 mast cell인 HMC-1 cells에서 hypoxia-inducible factor-1 (HIF-1)${\alpha}$의 작용을 관찰하였다. 결과 : PMA+A23187은 대조군과 비교해서 interleukin $(IL)-1{\beta}$, IL-6와 tumor necrosis factor $(TNF)-{\alpha}$의 분비를 증가시킨다. 또한 증가된 cytokines IL-1, IL-6, $TNF-{\alpha}$가 인삼의 처리에 의해 두드러지게 억제하는 것을 확인하였다. 인삼(5 ${\mu}g/ml$)은 $IL-1{\beta}$, IL-6, $TNF-{\alpha}$의 분비를 약 105.1${\pm}$9.7%, 95${\pm}$9.4%, 29.7${\pm}$4.5%,(P<0.05)로 최대로 억제하였고, PMA+A23187에 유도된 vascular endothelial growth factor (VEGF)와 granulocyte macrophage-colony stimulating factor (GM-CSF)의 분비를 41.3%와 75.7%로 각각 억제하였다. 그리고 저자는 인삼이 PMA+A23187로 유도된 HIF-1${\alpha}$ 발현과 HIF-1에 대해 DNA binding activity를 억제하고 있음을 관찰하였다. 결론 : 인삼이 HIF-1에서 염증반응을 억제함을 나타내고, 이는 인삼이 염증성 질환을 치료하는데 유익한 효과가 있음을 의미한다. Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation

Kim, Shin Young,Jin, Cheng-Yun,Kim, Cheol Hong,Yoo, Young Hyun,Choi, Sung Hyun,Kim, Gi-Young,Yoon, Hyun Min,Park, Hwan Tae,Choi, Yung Hyun UNKNOWN 2019 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.43 No.2

<P>Isorhamnetin, which is a flavonoid predominantly found in fruits and leaves of various plants, including <I>Hippophae rhamnoides</I> L. and <I>Oenanthe javanica</I> (Blume) DC, is known to possess various pharmacological effects. However, the anti-inflammatory potential of isorhamnetin remains poorly studied. Therefore, the present study aimed to investigate the inhibitory potential of isorhamnetin against inflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. To measure the effects of isorhamnetin on inflammatory mediators and cytokines, and reactive oxygen species (ROS) generation, the following methods were used: cell viability assay, griess assay, ELISA, reverse transcriptase-polymerase chain reaction, flow cytometry, western blotting and immunofluorescence staining. The results revealed that isorhamnetin significantly suppressed LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E<SUB>2</SUB>, without exhibiting significant cytotoxicity. Consistent with these results, isorhamnetin inhibited LPS-stimulated expression of regulatory enzymes, including inducible NO synthase and cyclooxygenase-2 in BV2 cells. Isorhamnetin also downregulated LPS-induced production and expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. The mechanism underlying the anti-inflammatory effects of isorhamnetin was subsequently evaluated; this flavonoid inhibited the nuclear factor (NF)-κB signaling pathway by disrupting degradation and phosphorylation of inhibitor κB-α in the cytoplasm and blocking translocation of NF-κB p65 into the nucleus. In addition, isorhamnetin effectively suppressed LPS-induced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88. It also suppressed the binding of LPS with TLR4 in BV2 cells. Furthermore, isorhamnetin markedly reduced LPS-induced generation of ROS in BV2 cells, thus indicating a strong antioxidative effect. Collectively, these results suggested that isorhamnetin may suppress LPS-mediated inflammatory action in BV2 microglia through inactivating the NF-κB signaling pathway, antagonizing TLR4 and eliminating ROS accumulation. Further studies are required to fully understand the anti-inflammatory effects associated with the antioxidant capacity of isorhamnetin; however, the findings of the present study suggested that isorhamnetin may have potential benefits in inhibiting the onset and treatment of neuroinflammatory diseases.</P>