• 대한한방부인과학회지
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• 제21권2호
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• pp.166-183
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• 2008

Purpose: This study was performed to determine anti-imflammatory effects of Haedoksamultang. Methods: In this study, I examined the effects of Haedoksamultang on the production of nitric oxide(NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), and interlukin-1${\beta}$(IL-1${\beta}$) as well as the expression of inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), TNF-${\alpha}$, and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited LPS-stimulated NO production. Western blotting and RT-PCR analysis showed that Haedoksamultang suppressed LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 cells. Haedoksamultang also suppressed the expression and production of LPS-stimulated TNF-${\alpha}$ and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited NF-${\kappa}B$ activation in LPS-treated RAW 264.7 cells. Moreover, this compound blocked $I{\kappa}B-{\alpha}$ phosphorylation and nuclear translocation of the cytosolic NF-${\kappa}B$ p65 subunit, which highly correlated with the production and expression of inflammatory mediators. Results: Haedoksamultang suppresses that inflammation-associated gene expression by blocking NF-${\kappa}B$ activation. Conclusion: These results suggest that Haedoksamultang may be beneficial for treating inflammatory disease.

• 대한한방내과학회지
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• 제34권2호
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• pp.204-214
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• 2013

Objectives : This study was designed to investigate the cellular and molecular mechanisms of anti-inflammatory activity of the water extract of Polygala tenuifolia Willd. (Pt-WE). Methods : Using lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells, we examined inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$). Also, the inhibitory effect of Pt-WE on the activity of activator protein 1 (AP-1) and upstream signaling molecules was evaluated. To assess the protective effect of Pt-WE on hydrochloride/ethanol (HCl/EtOH)-induced gastric ulcer in mice, we compared Pt-WE (200 mg/kg) with ranitidine (50 mg/kg) treated mice's gastric mucosa, based on gross observations. Results : Pt-WE inhibited LPS-induced production of NO, $PGE_2$ in a dose-dependent manner, without causing cytotoxicity. Pt-WE suppressed AP-1 activation by reducing generations of both c-Jun and c-Fos. In addition, Pt-WE inhibited the p-MKK 4/7 (mitogen-activated protein kinase kinase 4/7) and p-JNK (c-Jun N-terminal kinase) 1 in LPS-stimulated RAW264.7 cells. HCl/EtOH-induced gastric ulcer lesions were inhibited by pre-treatment of Pt-WE based on gross observations. In addition, Pt-WE decreased the phosphorylation level of JNK. Conclusions : These results demonstrate that Pt-WE has anti-inflammatory and gastroprotective effects. Thus, Pt-WE may be used widely in treatment of not only neurodegenerative diseases but also inflammatory diseases.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.454-461
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• 2013

The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitricoxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.481-486
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• 2013

Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents.

• 한국식품영양학회지
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• 제31권4호
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• pp.495-501
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• 2018

Ultraviolet B (UVB) exposure is a risk factor for skin damage resulting in oxidative stress, inflammation, and cell death. The purpose of this study was to investigate the physicochemical properties of Platycodon grandiflorum (PG) to improve its biological activities using a three-step steaming process. We investigated the protective effects of PG and steamed PG extracts on human dermal fibroblasts (HDFs) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the PG extracts was evaluated by measuring the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging activity. ABTS and DPPH were shown by the 0, 30, and 70% ethanol extracts of 2S-PG and 3S-PG ($IC_{50}$, 28~45 and $27{\sim}30{\mu}g/mL$, respectively). Treatment of UVB-irradiated cells with steamed PG ($25{\sim}400{\mu}g/mL$) did not affect their viability. The streamed PG extract suppressed UVB-induced generation of reactive oxygen species (ROS). In addition, streamed PG extract reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated HDF, regulating nuclear factor $(NF)-{\kappa}B$ expression. These findings suggest that steamed PG extract may be potentially effective against inflammation associated with UVB-induced oxidation stress.

• 대한한의학회지
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• 제22권3호
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• pp.92-97
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• 2001

목적 :본 연구는 최근 임상에서 많이 사용하는 자하거 약침액이 과산화수소($H_2O_2$)로 야기된 송과선 세포의 Apoptosis에 있어서 세포 보호에 미치는 영향과 그 기전을 분석하였다. 방법 :송과선 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전을 관찰하기 위하여 면역세포화학법. 세포화학법 및 reverse transcription-polymerase chain reaction (RT-PCR)을 시행하였다. 결과 : 자하거 약침액 투여군에서는 nuclear factor kappa B (NFkB), inducible nitric oxide synthase (iNOS), nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase의 발현이 $H_2O_2$ 투여군보다 감소하였다. RT-PCR에서는 caspase-3의 발현이 자하거 약침액 투여군에서 $H_2O_2$ 투여군보다 억제되었다. 결론： 이상의 결과를 통하여 자하거 약침액이 $H_2O_2$로 유발된 Apoptosis에서 세포보호 효과가 있으며 그 기전은 iNOS와 caspase-3의 억제에 기인할 가능성을 시사한다고 하겠다.

• IMMUNE NETWORK
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• 제10권6호
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• pp.212-218
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• 2010

Backgroud: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. Methods: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-${\kappa}B$, Nrf2 and MAPK activation in mouse peritoneal macrophages. Results: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-${\kappa}B$ activation, phosphorylation and degradation of $I{\kappa}B-{\alpha}$, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. Conclusion: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-${\kappa}B$ suppression and HO-1 induction.

• International Journal of Oral Biology
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• 제39권4호
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• pp.207-213
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• 2014

Antimicrobial actions of reactive oxygen/nitrogen species (ROS/RNS) derived from products of NADPH oxidase and inducible nitric oxide (NO) synthase in host phagocytes inactivate various bacterial macromolecules. To cope with these cytotoxic radicals, pathogenic bacteria have evolved to conserve systems necessary for detoxifying ROS/RNS and repairing damages caused by their actions. In response to these stresses, bacteria also induce expression of molecular chaperones to aid in ameliorating protein misfolding. In this study, we explored the function of a newly identified chaperone Spy, that is localized exclusively in the periplasm when bacteria exposed to conditions causing spheroplast formation, in the resistance of Salmonella Typhimurium to ROS/RNS. A spy deletion mutant was constructed in S. Typhimurium by a PCR-mediated method of one-step gene inactivation with ${\lambda}$ Red recombinase, and subjected to ROS/RNS stresses. The spy mutant Salmonella showed a modest decrease in growth rate in NO-producing cultures, and no detectable difference of growth rate in $H_2O_2$ containing cultures, compared with that of wild type Salmonella. Quantitative RT-PCR analysis showed that spy mRNA levels were similar regardless of both stresses, but were increased considerably in Salmonella mutants lacking the flavohemoglobin Hmp, which are incapable of NO detoxification, and lacking an alternative sigma factor RpoS, conferring hypersusceptibility to $H_2O_2$. Results demonstrate that Spy expression can be induced under extreme conditions of both stresses, and suggest that the protein may have supportive roles in maintaining proteostasis in the periplasm where various chaperones may act in concert with Spy, thereby protecting bacteria against toxicities of ROS/RNS.

• 대한본초학회지
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• 제30권1호
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• pp.85-93
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• 2015

Objectives : Bilobalide (BIL) is a predominant sesquiterpene trilactone constituent that accounts for a partial portion of the standardized Ginkgonis Folium extract, which has been widely used to treat a variety of neurological disorders involving cerebral ischemia and neurodegeneration. In this study, it was tested whether BIL exhibits anti-inflammatory activities on inflammation response, or not. Methods : To elucidate the molecular mechanisms of BIL on pharmacological and biochemical actions in inflammation, we examined the effect of BIL on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation was focused on how BIL affect on inflammation-related mediators including various signals such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), interleukin-6(IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), mitogen-activated protein kinases(MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) in LPS-stimulated RAW 264.7 cells. Results : We found that BIL inhibited LPS-induced NO, $PGE_2$, IL-6 and $TNF-{\alpha}$ productions as well as the expressions of iNOS and COX-2. Furthermore, BIL suppressed the LPS-induced phosphorylation for MAPK activation. Conclusions : These results suggest that BIL has inhibitory effects on LPS-induced $PGE_2$, NO, IL-6 and $TNF-{\alpha}$ production, as well as the expressions of iNOS and COX-2 in the murine macrophage. It seems that these inhibitory effects occur by blocking the phosphorylation of MAPKs for activation. Then, BIL suppressed the activation of nuclear factor $NF-{\kappa}B$ in nucleus. These observations suggest that BIL has anti-inflammatory effect by inhibiting.

• 대한본초학회지
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• 제35권6호
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• pp.55-68
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• 2020

Objectives : We observed the possibilities that blue honeysuckle has favorable analgesic or refinement effects on the Primary dysmenorrhea (PD) in rats. Methods : Estradiol benzoate and oxytocin were used to induce the PD rat model. And Blue honeysuckle concentration lyophilized powders (BH) 500, 250 and 125 mg/kg and 500 mg/kg of Lonicerae Flos aqueous extract lyophilized powders (LF) were orally administered, once a day for 10 days at 30 min after each estradiol benzoate treatment. Then the changes on the body weights and gains during experimental periods, abdominal writhing response for analgesic activities, uterine weights, uterus lipid peroxidation, antioxidant defense system - glutathione contents, superoxide dismutase and catalase activities, NF-κB and COX-2 mRNA expressions were monitored with uterus histopathology including immunohistochemistry for tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS).. Results : Inflammatory and oxidative stress mediated PD signs were favorably and dose-dependently inhibited by 10 days continuous oral administration of three different dosages of BH - 500, 250 and 125 mg/kg as comparable to those of indomethacin(IND) 5 mg/kg treated rats in BH 500 mg/kg administered PD rats, and similar to those of LF 500 mg/kg in BH 125 mg/kg, at least in a condition of the present PD rat model. Conclusions : The results suggest that BH has favorable analgesic and refinement activities on the estradiol benzoate and oxytocin treatment-induced PD signs through anti-inflammatory and antioxidative potentials.