• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.441-449
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• 2015

Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-${\alpha}$ in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-${\kappa}B$-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-${\kappa}B$ nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-${\kappa}B$ activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-${\kappa}B$ activation.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.401-411
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• 2015

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• 한방재활의학과학회지
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• 제30권4호
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• pp.41-53
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• 2020

Objectives The purpose of this study was to investigate the effects of Silbi-san on the antioxidant and fat accumulation inhibition and to analyze the anti-obesity effect by analyzing the changes in serum lipid composition in obese mice. Methods We compared contents of phytochemicals like total polyphenols and total flavonoid and antioxidant activities such as 2,2-dipheny-1-picrylhydrazyl and 2.2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity. After Silbi-san in 3T3-L1 cells in vitro and mouse adipose tissue ex vivo, we quantified intracellular triglyceride accumulation and lipolysis. Moreover, the anti-obesity activity though inhibiting pancreatic lipase were analyzed. In 3T3-L1 cells, morphological changes showed that control cells had many lipid while cells treated with Silbi-san had less lipid accumulation. 30% EtOH Silbi-san treatment also suppressed the fat absorption by inhibiting the activity of pancreatic lipase and led to high lipolysis through promoting glycerol release. The experimental group was divided into four groups: Normal group fed normal feed, Control group fed 60% high fat diet (HFD) and distilled water, drug group fed 60% high fat diet and 200 mg/kg of Silbi-san water extract, drug group fed 60% HFD and 200 mg/kg of Silbi-san 30% ethanol extract. Results Serum total cholesterol content and serum low density lipoprotein-cholesterol content were significantly decreased in the Silbi-san extract group compared to the control group, serum high density lipoprotein-cholesterol content was significantly increased in Silbi-san extract group. Conclusions In this study, the antioxidant and fat accumulation inhibitory effects of Silbi-san were confirmed.

• 혜화의학회지
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• 제10권2호
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• pp.11-19
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• 2002

To evaluate the antitumor activity and antimetastatic effects of Bruceae FructusCBF), studies were done experimentally. The results were obtained as follows : 1. In cytotoxicity against A549, SK-MEL-2, MCF-7 and XF498 cell concentration inhibiting cell growth up to below 50% of control was recognized at $25{\mu}g/m{\ell}$ of BF. Also BF inhibited cell growth up to below 50% of control against HCT15 cell at $12.5{\mu}g/m{\ell}$, so it showed stronger cytotoxicity against HCT15 cell than another cancer cell. 2. In Inhibitory effect on activity of DNA topoisomerase- I, the $IC_{50}$ was shown $10-50{\mu}g/m{\ell}$ of BF. 3. The T/C% was 143.4 in BF treated group in S-180 bearing ICR mice. 4. The concentration inhibiting adhesion of A549 and SK-OV-3 to complex extracellular matrix up to below 30% of control was recognized at $1{\mu}g/m{\ell}$ of BF. 5. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in BF treated group as compared with control group. These results suggested that BF extracts might be usefully applied for prevention and treatment of cancer.

• 혜화의학회지
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• 제9권2호
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• pp.97-109
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• 2001

To evaluate the antitumor activity and antimetastatic effects of HDBT, studies were done experimentally. The results were obtained as follows: 1. HDBT extracts didn't show cytotoxicity against BALB/C mouse lung fibroblast cell. 2. In cytotoxicity against A549, SK-OV-3, B16-BL6 and HT1080 concen- tration inhibiting cell growth up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 3. The concentration inhibiting adhesion of A549 and B16-BL6 to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 4. In Inhibitory effect on activity of DNA topoisomerase I, the $IC_{50}$ was shown $200-300{\mu}g/m{\ell}$ of HDBT. 5. The T/C% was 137.9% in HDBT-treated group in S-180 bearing ICR mice. 6. In CAM assay, HDBT extracts inhibited angiogenesis significantly at $15{\mu}g/egg$ concentration as compared with control. 7. In pumonary colonization assay, a number of colonies in the lungs were decreased but insignificantly in HDBT-treated group as compared with control group. 8. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased significantly in HDBT-treated group but numbers PLT were increased insignificantly as compared with control. From above results it was concluded that HDBT could be usefully applied for the prevention and treatment of cancer.

• 대한수의학회지
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• 제56권1호
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• pp.29-35
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• 2016

When exposed to gamma-rays, hair follicular cells immediately go through apoptosis, which hampers their rapid differentiation essential for the regeneration of hair. Phloroglucinol (PG) is a phenolic compound of Ecklonia cava, brown algae abundant in Jeju island, Korea. Containing plentiful polyphenols, PG is known for its instructive effects by inhibiting apoptosis, scavenging oxygen radicals, and protecting cells against oxidative stress. In this study, we demonstrate that PG rescues radiosensitive hair follicular cells from gamma radiation-induced apoptosis and DNA damage. To identify protective capacity of PG on hair follicles, we irradiated with 8.5 Gy (1.5 Gy/min) of gamma-rays to the whole body of C57BL/6 mice at day 6 after depilation with or without PG. In mice exposed to radiation, the expression of proapoptotic molecule p53 was downregulated in the skin of PG treated group. On immunohistochemical observation of the skin, PG inhibited the immunoreactivity of p53 and cleaved caspase-3. PG treatment protected hair follicular cells from cell death due to gamma-radiation. Our results suggest that PG presents radioprotective effects by inhibiting apoptosis of radiosensitive hair follicular cells and can protect hair follicular cells from gamma-ray induced damage.

• Weed & Turfgrass Science
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• 제1권4호
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• pp.50-56
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• 2012

본 연구의 목적은 bar 유전자를 발현한 형질전환벼에 대한 글루타민 합성효소 저해제인 glufosinate-ammonium, L-metionine sulfoximine과 광합성저해제인 paraquat에 저항성 수준과 형질전환벼와 비형질전환벼의 암모늄 축적량, 저온반응 및 수량을 비교하는데 있다. 형질전환벼 계통은 비형질전환벼에 비해 glufosinate-ammonium에 45~95배 높은 저항성을 보였다. 한편 형질전환벼 계통은 L-metionine sulfoximine을 처리했을 때도 형질전환벼 계통이 비형질전환벼에 비해 18배 이상의 저항성을 보여 교차저항성이 있음을 확인할 수 있었다. 그러나 glufosinate-ammonium과 작용기작이 다른 제초제인 paraquat에 대한 다중저항성은 없었다. Glufosinate-ammonium 처리에 의해 ammonium 축적은 비형질전환벼에서 증가하였으나 모든 형질전환벼의 계통에서는 적거나 효과가 없었다. 형질전환벼 계통 258, 411, 607 및 608을 제외한 계통은 비형질전환벼에 비해 저온 내성 및 저온 후 회복정도가 유의적으로 낮은 경향을 보였다. 형질전환벼 계통 142, 144, 258 및 608의 수량은 비형질전환벼와 유사하거나 높았다.

• 한국식품영양과학회지
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• 제29권2호
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• pp.204-210
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• 2000

The antioxidative effects of solvent fractions of kimchi on LDL oxidatiojn in vitro as well as hypolipidemic effects of these fractions in rabbit fed atherogenic diet were studied. Methanol extract of deffated kimchi was fractionated sequentially with dichloromethane, ethylacetate, butanol and water. All solvent fractions of kimchi inhibited Cu2+-induced LDL oxidation. Among these fractions, the dicholoromethane fraction at the concentration of 25$\mu\textrm{g}$/mL showed the highest antioxidant effects against LDL oxidation in the aspect of inhibiting TBARS production by 28.03% or prolonged lag phase duration 2-fold compared to those of control. Based on the results from in vitro study, New Zealand White Rabbits grouped six each were fed for 8 weeks either basal diet containing 1% cholesterol or experimental diet containing dichloromethane, ethylacetate or water fraciton added to the basal diet. The amount of solvent fraction of kimchi added to the experimental diet was equivalent to 5% of freeze-dried kimchi. The hypolipidemic effects was observed from all experimental gropus, especially from dichloromethane fraction added group. The plasma and LDL cholesterol levels of this group were decreased by 49% and 47%, respectively while that of HDL increased by 91% compared to those of control. The calculated atherogenic index for the dichloromethane group was the lowest among groups. However, TG lowering effect of experimental group was not observed since solbent fraction of kimchi was used instead of freeze-dried kimchi. The TBARS concentration of LDL isolated from rabbit fed dichloromethane fraction was decreased 21% than that of control. These results indicate that active principles responsible for inhibiting LDL oxidation and lowering plasma cholesterol may present abundantly in dichloromethane fraction of kimchi.

• Journal of Ginseng Research
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• 제43권2호
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• pp.236-241
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• 2019

Background: Thromboxane A2 ($TXA_2$) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a $Ca^{2+}-antagonistic$ antiplatelet effect, whether it inhibits $Ca^{2+}-dependent$ cytosolic phospholipase $A_2$ ($cPLA_{2{\alpha}}$) activity to prevent the release of arachidonic acid (AA), a $TXA_2$ precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated $TXA_2$ inhibition. Methods: We investigated whether G-Ro attenuates $TXA_2$ production and its associated molecules, such as cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS), $cPLA_{2{\alpha}}$, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. Results: G-Ro reduced $TXA_2$ production by inhibiting AA release. It acted by decreasing the phosphorylation of $cPLA_{2{\alpha}}$, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets. Conclusion: G-Ro inhibits AA release to attenuate $TXA_2$ production, which may counteract $TXA_2-associated$ thrombosis.