• 한국식품과학회지
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• 제46권1호
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• pp.61-67
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• 2014

본 연구에서는 생 들깨와 볶은 들깨의 염증매개물질 감소 효과를 RAW 264.7 대식 세포와 궤양성 대장염이 유도된 마우스를 이용하여 비교 분석하고자 하였다. LPS 처리에 의해 활성화된 RAW 264.7 대식세포에서 들깨의 에탄올 추출물은 볶음 여부와는 관계없이 NO, IL-6, TNF-${\alpha}$와 같은 염증매개물질 수준을 유의적으로 감소시키는 효과(대조군 대비 45-85% 수준)가 있었다. 반면 DSS 처리에 의해 궤양성 대장염이 유도된 마우스 모델에서는, 볶은 들깨 식이(1%)만이 대장의 $PGE_2$, $LTB_4$와 같은 염증매개물질 수준을 유의적으로 감소시키는 효과(각각 대조군 대비 34%, 58% 수준)가 있었다. 이와 같은 연구 결과를 종합하여 보면, 볶은 들깨는 in vitro 항염성 뿐 아니라 in vivo 항염성을 가지는 것으로 판단된다. 앞으로 들깨의 볶음 과정에서 생성된 항염 기능 성분들을 분리 동정하는 연구와 볶은 들깨의 항염성과 관련된 기전에 관한 후속 연구가 지속적으로 이루어진다면 볶은 들깨가 대장염을 포함한 여러 염증관련 질병 예방에 유용한 소재로 이용될 수 있을 것으로 기대된다.

• 대한본초학회지
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• 제26권1호
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• pp.41-46
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• 2011

Objectives : To quantitate the main compounds and investigate the biological activity of Sosiho-tang (Xiao-Chai-Hu-Tang, SST), simultaneous determination of baicalin and glycyrrhizin, and anti-inflammatory activity were estimated. Methods : A quantitative analysis was performed using a high performance liquid chromatography (HPLC). Reference compounds were separated on a reversed-phase column using gradient elution with water and acetonitrile each containing acetic acid at a flow rate of 1 mL/min. And the productions of nitric oxide (NO) and prostaglandin $(PE)E_2$ were examined by lipopolysaccharide (LPS)-treated RAW 264.7 cells in the presence of the SST. The anti-inflammatory activity of SST was investigated by carrageenin-induced paw edema in rats. The paw volume was measured at 2 and 4 hr following carrageenin-induced paw edema in rats. Results : The correlation coefficients of the compounds showed good linearity ($r^2$ > 0.9992) over the linear range. The precisions of intra- and inter-day were less than 7.0% of relative standard deviation (RSD) values for baicalin and less than 3.5% of RDS valuse for glycyrrhizin. Recovery rates were within the range of 95.41-101.5%. The contents of baicalin and glycyrrhizin in SST were average 70.52, 6.18 mg/g, respectively. And SST exhibited inhibitory effect on NO production in LPS-treated RAW 264.7 cells but not on $PGE_2$ production. Oral administration of SST (1 g/kg) showed a reduction in carrageenin-induced paw edema on rats. Conclusions : The analytical method was applied successfully to measure the contents of baicalin and glycyrrhizin in SST which exhibited anti-inflammatory activities.

• 한국식품과학회지
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• 제48권6호
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• pp.590-596
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• 2016

본 연구에서는 우리나라에서 가장 많이 재배되고 있는 캠벨어얼리 포도 품종에서 포도가지를 대상으로 산화방지, 항염증 및 항가려움증 효과를 검증하고 활성물질을 나타내는 지표물질을 추적 조사하였다. 그 결과 포도가지 추출물의 총 폴리페놀과 총 플라보노이드 함량은 각각 $201.42{\pm}4.16$과 $11.85{\pm}0.44mg\;GAE/g$으로 조사되었다. 또한 캠벨어얼리 포도가지 추출물의 ABTS와 DPPH 라디칼 소거 활성은 각각 $45.60{\pm}0.09$ ($IC_{50}$)과 $299.13{\pm}0.22$ ($IC_{50}$)으로 나타나 산화방지 활성이 우수하였다. 게다가 캠벨어얼리 포도가지 추출물은 지방질다당류로 활성화된 RAW 264.7 세포에서 전염증성 매개물인 산화질소와 프로스타글란딘 $E_2$를 iNOS와 COX-2 분자 발현 억제를 통하여 억제하였고, 전염증성 사이토카인인 인터류킨-1베타와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 더욱이 phorbol 12-myristate 13-acetate (PMA)와 calcium ionophore A23187로 활성화된 인간 유래 비만세포인 HMC-1 세포에서 종양괴사인자-알파와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 마지막으로 Compound 48/80으로 유도되는 마우스 가려움증을 캠벨어얼리 포도가지 추출물은 효과적으로 억제하였다. 이러한 캠벨어얼리 추출물에서 활성을 나타내는 물질을 추적한 결과 레스베라트롤의 함량이 높게 검출되었다. 그러므로 본 연구의 결과를 종합해 볼 때 캠벨어얼리 포도가지 추출물은 아토피 질환에서 나타나는 염증과 가려움증을 효과적으로 제어할 수 있는 효과적인 소재임을 제시하였다.

• 생약학회지
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• 제47권1호
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• pp.7-11
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• 2016

The aerial part of Trichosanthes kirilowii Maxim. (Cucurbitaceae), has long been used in traditional Korean and Chinese medicines for the treatment of heatstroke. We isolated and identified three flavones, luteolin-7-O-${\beta}$-D-glucopyranoside(1), luteolin-4'-O-${\beta}$-D-glucopyranoside(2), luteolin(3) from its methanolic extract. In the present study, we found that luteolin attenuates the lipopolysaccharide(LPS)-induced inflammation in BV2 microglial cells. Luteolin significantly inhibited LPS-induced production of pro-inflammatory mediators such as nitric oxide(NO) and prostaglandin $E_2(PGE_2)$ in BV2 microglia in a concentration-dependent manner without cytotoxic effect. Luteolin dose-dependently suppressed the protein expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2). In addition, luteolin also showed significant induction of heme oxygenase(HO)-1. These results suggest that both the aerial part of T. kirilowii and luteolin may be good candidates to regulate LPS-induced inflammatory response.

• 대한한의학회지
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• 제30권1호
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• 한국식품영양과학회지
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• 제35권1호
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• pp.28-34
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• 2006

갈근(Puerariae Radix)의 $70\%$ ethanol 추출물 중 ethyl acetate 분획물(EPR)은 염증성 cytokine을 처리한 마우스 대식세포 및 토기 연골조직세포에서 염증의 발현과 관련된 NO 생성 저해효과를 보였고, 관절조직의 주요 성분 중 하나인 proteoglycan의 분해 억제효과와 관절조직 분해효소인 MMP-9의 활성이 억제되었다. 또한, 통증유발물질인 프로스타글란딘의 유의성 있는 감소를 보여 통증억제 효과가 있음을 확인하였을 뿐만 아니라 초산 유발 진통 효과테스트인 동물 모델에서도 효과적으로 통증을 억제함을 확인하였다. 즉, 갈근의 $70\%$ ethanol 추출물 중 ethyl acetate 분획물(EPR)은 독성의 문제뿐만 아니라, 소염, 진통 효과 및 연골 조직세포의 분해를 억제하는 다양한 효과를 나타내는 장점을 지니고 있어 관절염 치료제의 훌륭한 후보약재가 될 것으로 기대된다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Journal of Nutrition and Health
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• 제56권3호
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• pp.231-246
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• 2023

본 연구에서는 MIA로 골관절염을 유도한 SD 흰쥐에서 인도산 보스웰리아 검레진을 주정 추출 후, 헥산으로 지방 제거 공정을 추가하여 제조한 보스웰리아 검레진 추출물인 FJH-UBS의 항골관절염 효능을 평가하기 위해 실시하였다. FJH-UBS는 40 또는 80 mg/kg BW/day 용량으로 5주간 경구투여하였고, FJH-UBS를 2주간 투여 후 MIA (3 mg/50 µL/rat)를 무릎 관절강 내에 주사하여 골관절염을 유도하였다. MIA 유도 골관절염 동물모델에서 FJH-UBS는 무릎 관절의 부종을 감소시키고 연골의 분해를 억제하였으며, 연골 내 type II collagen과 aggrecan 발현을 증가시켰다. FJH-UBS (80 mg/kg BW/day)는 혈청 내 PGE2, LTB4, IL-1β, 및 IL-6 함량을 감소시켰고, MMP-13 함량을 감소시켰다. FJH-UBS (80 mg/kg BW/day)는 연골 활막 내 iNOS, COX-2, 5-LOX, IL-1β, IL-6 및 TNF-α 발현을 감소시켰고, MMP-2, MMP-9 및 MMP-13 발현을 감소시켰다. 이 결과는 FJH-UBS가 염증매개물질과 염증성 cytokine의 발현감소를 통해 염증 반응을 억제하고, MMPs의 발현을 억제하여 연골 기질의 분해를 억제함으로서 항골관절염 효능을 나타냄을 의미하며 이는 관절 및 연골 건강 개선 기능성 원료로 FJH-UBS의 활용 가능성을 제시한다.

• Journal of Microbiology and Biotechnology
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• 제18권3호
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• pp.523-531
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• 2008

Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only ${\gamma}$-irradiation led to cell cycle arrest at the $G_1$ phase. On the other hand, co-treatment with genistein and ${\gamma}$-irradiation caused a decrease in the $G_1$ phase and a concomitant increase up to 56% in the number of $G_2$ phase. In addition, co-treatment increased the expression of p53 and p21, and Cdc2-tyr-15-p, supporting the occurrence of $G_2/M$ arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, down regulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and ${\gamma}$-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and ${\gamma}$-irradiation almost completely prevented irradiation-induced COX-2 expression and $PGE_2$ production. Co-treatment with genistein and ${\gamma}$-irradiation inhibited proliferation through $G_2/M$ arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.