• Biomolecules & Therapeutics
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• 제20권1호
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• pp.96-103
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• 2012

In the present study, the inhibitory effect of neem leaf extract (NLE) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production was examined both in vitro and in vivo. In vitro study revealed that NLE treatment ($100{\mu}g/ml$) inhibits LPS (100 ng/ml)-induced NO production by 96% and TNF-${\alpha}$ production by 32%. The reduction in NO production is probably conferred by the complete suppression of inducible nitric oxide synthase (iNOS) expression. Interestingly, in vivo NLE significantly improved the survival rate of mice in an experimental sepsis model. Administration of NLE (100 mg/kg) 24 h before LPS treatment (20 mg/kg) improved the survival rate of mice by 60%. The inhibition of plasma NO and TNF-${\alpha}$ production by NLE is likely to account for the improved survival of mice. Our results suggest that NLE may present a promising avenue in the development of therapeutic agents for the treatment of inflammatory diseases.

• 동의생리병리학회지
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• 제20권4호
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• pp.957-965
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• 2006

This study was peformed to evaluate antithrombotic activities and anti-inflammatory effects of Kami-BoyangHwanoh-Tang(KBHT). The major findings were summarized as follows. In experiment of anti-thrombotic effect; KBHT inhibited human platelet aggregation induced by ADP and epinephrine as compared with the control group and inhibited pulmonary embolism induced by collagen and epinephrine (inhibitory rate is 50 %). KBHT increased platelet number significantly and also KBHT shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. In experiment of anti-inflammatory effect; KBHT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression as compared with the control group in a concentration-dependent degree, and inhibited NO production significantly at 50, $100\;{\mu}g/^{ml}$, and also inhibited ROS production in a concentration-dependent degree as compared with the control group in RAW 264.7 cell line. KBHT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, and also decreased IL-6 and $TNF-{\alpha}$ production in liver tissue, but increased $IL-1{\beta}$ production in liver tissue of acute inflammation-induced mice. KBHT increased survival rate at 3rd day in mice with lethal endotoxemia induced by LPS. These results suggest that KBHT can be useful in treating diverse female diseases caused by thrombosis and inflammation such as endometrosis, myoma, pelvic congestion, chronic cervicitis, chronic pelvic inflammatory disease and so on.

• 동의생리병리학회지
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• 제29권1호
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• pp.11-17
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• 2015

Overconsumption of fructose results in dyslipidemia, hypertension, which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of Rubus coreanus Miq.(RCM) in high-fructose diet-induced metabolic syndrome. Animals were divided into three groups; Control group fed regular diet and tap water, fructose groups were fed the 65% high-fructose (HF) diet with/without RCM 100 mg/kg/day for 8 weeks, respectively. Chronic treatment with RCM significantly decreased body weight, fat weight and adipocyte size. Moreover, RCM significantly prevented the development of the metabolic disturbances such as hyperlipidemia and hypertension. RCM also led to increase in high density lipoprotein level in the HF group. In addition, RCM suppressed vascular cell adhesion molecule-1 (VCAM-1) expression and significantly recovered the levels of endothelial nitric oxide synthase (eNOS) expression in aorta. These results demonstrates that RCM may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, and hypertension.

• Food Science and Biotechnology
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• 제17권4호
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• pp.745-750
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• 2008

Anti-inflammatory potential of the enzymatic extract prepared by Kojizyme (ECK), a component of brown seaweeds Ecklonia cava (Alariaceae, Phaeophyta) in vivo was investigated. For the application of mouse ear edema model, 12-O-tetradecanoylphorbol acetate (TPA) was used, a topical inducer of a long-lasting inflammatory response. Our results demonstrated that ECK inhibited ear edema when topically applied to mouse ear skin. In histological evaluation, the inhibition activity of ECK on TPA-induced inflammation is similar to that of dexamethasone, although less strong. In addition, the mRNA expression levels of IL-$1{\beta}$, IFN-$\gamma$, TNF-$\alpha$, and cyclooxygenase-2 (COX2) and the immunoreactivity to inducible nitric oxide synthase (iNOS) and COX2 expressed mainly in inflammatory cells were down-regulated by ECK. These results indicate that ECK has anti-inflammatory effects through the inhibition of Th1 cytokines and 2 inducers of inflammation in TPA-induced ear skin edema.

• 대한한방부인과학회지
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• 제20권3호
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• pp.45-64
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• 2007

Purpose: This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of NeungaSoJeokTang water extract (NSJT). Methods: In the study of anti-inflammatory effects, NSJT was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFC) and RAW 264.7 cells. Results: Prior to the experiment, we evaluated sGOT, sGPT, BUN and creatine after the treatment. As a result, NSJT was innoxious on liver and kidney. In experiment of anti-thrombotic effect, NSJT inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. NSJT did not affect significantly the blood flow rate both in vitro and in vivo. NSJT increased platelet number and fibrinogen amount, and NSJT shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, NSJT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. NSJT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, but increased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in liver tissue. NSJT increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion: These results suggest that NSJT can be used for treating diverse female diseases caused by thrombosis and inflammation such as pelvic pain, pelvic inflammatory disease as well as vulvar pain due to vulvitis, vulvar vestibulitis and so on.

• BMB Reports
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• 제54권10호
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• pp.528-533
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• 2021

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.

• Laboraroty Animal Research
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• 제33권1호
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• pp.40-47
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• 2017

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-${\alpha}$, interleukin (IL)-6 and IL-$1{\beta}$ in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1069-1078
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• 2021

Sevoflurane postconditioning (SPostC) has been proved effective in cardioprotection against myocardial ischemia/reperfusion injury. It was also reported that heat shock protein 70 (HSP70) could be induced by sevoflurane, which played a crucial role in hypoxic/reoxygenation (HR) injury of cardiomyocytes. However, the mechanism by which sevoflurane protects cardiomyocytes via HSP70 is still not understood. Here, we aimed to investigate the related mechanisms of SPostC inducing HSP70 expression to reduce the HR injury of cardiomyocytes. After the HR cardiomyocytes model was established, the cells transfected with siRNA for HSP70 (siHSP70) or not were treated with sevoflurane during reoxygenation. The lactate dehydrogenase (LDH) level was detected by colorimetry while cell viability and apoptosis were detected by MTT and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect HSP70, apoptosis-, cell cycle-associated factors, iNOS, and Cox-2 expressions. Enzyme-linked immuno sorbent assay (ELISA) was used to measure malondialdehyde (MDA) and superoxide dismutase (SOD). SPostC decreased apoptosis, cell injury, oxidative stress and inflammation and increased viability of HR-induced cardiomyocytes. In addition, SPostC downregulated Bax and cleaved caspase-3 levels, while SPostC upregulated Bcl-2, CDK-4, Cyclin D1, and HSP70 levels. SiHSP70 had the opposite effect that SPostC had on HR-induced cardiomyocytes. Moreover, siHSP70 further reversed the effect of SPostC on apoptosis, cell injury, oxidative stress, inflammation, viability and the expressions of HSP70, apoptosis-, and cell cycle-associated factors in HR-induced cardiomyocytes. In conclusion, this study demonstrates that SPostC can reduce the HR injury of cardiomyocytes by inducing HSP70 expression.

• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.15-26
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• 2022

Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.