• Journal of Life Science
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• v.24 no.9
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• pp.973-980
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• 2014

This study was conducted to explore new nutraceutical resources from the plant kingdom possessing biological activities. To fulfill this purpose, the anti-oxidative and anti-inflammatory activities of Decaisnea insignis ethanol extract (DIEE) were evaluated. First, DIEE possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid used as a positive control. Moreover, DIEE inhibited lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, DIEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1 (HO-1), and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The modulation of the HO-1 and Nrf2 expressions might be regulated by mitogen-activated protein kinases (MAPKs) and their upstream signaling pathways. On the other hand, DIEE suppressed LPS-induced nitric oxide (NO) formation without cytotoxicity. The inhibition of the NO formation was the result of the downregulation of inducible NO synthase (iNOS) by DIEE. The suppression of NO and iNOS by DIEE might be modulated by their upstream transcription factors, nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), and activator protein 1 (AP-1) pathways. Taken together, these results provide important new insights that D. insignis possesses anti-oxidative and anti-inflammatory activities. Therefore, it might be utilized as a promising material in the field of nutraceuticals.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.7-18
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• 2015

Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4. Methods: The 3D structure of ligands such as hydrogen peroxide ($H_2O_2$), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by $MM^+$ followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of $54{\times}55{\times}56$, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10. Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids. Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.639-652
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• 2006

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.406-412
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• 2012

This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride ($CCl_4$)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after $CCl_4$ injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin-3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. $CCl_4$ increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

• Korean Journal of Food Science and Technology
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• v.50 no.3
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• pp.349-355
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• 2018

Ginsenoside Rg5, one of the protopanaxadiol ginsenosides of wood-cultivated ginseng, has been implicated in various diseases, such as diabetes, cancer, and hypertension; however, its angiogenic activity and molecular mechanisms have not yet been elucidated. Here, we found that wood-cultivated ginseng extract and ginsenoside Rg5 increase in vitro proliferation, migration, and tube-like structure formation, which are typical phenomena associated with angiogenesis, in cultured human umbilical vein endothelial cells (HUVECs). Moreover, Ginsenoside Rg5 stimulated the phosphorylation of Akt, endothelial nitric oxide (NO) synthase (eNOS), and extracellular-regulated kinase (ERK)1/2, which are well-known signal mediators of the angiogenic pathway. Furthermore, Ginsenoside Rg5 did not accelerate the activation of ICAM-1 and VCAM-1 which are inflammatory response mediators. These results suggest that wood-cultivated ginseng extract and ginsenoside Rg5 stimulated in vitro angiogenesis by activating the Akt/eNOS- and ERK1/2-dependent signal pathways without inducing vascular inflammation.

• Journal of Nutrition and Health
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• v.51 no.1
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• pp.14-22
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• 2018

Purpose: Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice. Methods: Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days. Results: Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma $TNF-{\alpha}$ and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT. Conclusion: Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.348-354
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• 2020

Oryeong-san (ORS) is a traditional Korean herbal medicine widely used for renal associated diseases, composed of five medicine herbs; Atractylodes japonica Koidzumi, Cinnamomum cassia Presl, Polyporus umbellatus Fries, Poria cocos Wolf and Alisma orientale Juzepzuk. We studied to improve the convenience of intake and portability by developing modernized dosage forms, and examined the effect on anti-inflammation of ORS. In order to develop the tablet formulation of ORS (ORS-F), the tablets were evaluated on the basis of physical characteristics include diameter, thickness, weight variation, hardness, friability and disintegration. To analyze the marker components of ORS-F, eight index markers from five herbal medicines were chosen. And the method using high performance liquid chromatography (HPLC) with diode-array detector method was established for the simultaneous analysis. The biological activities were examined the effect of ORS-F on pro-inflammation mediated by LPS-stimulation. The production of nitric oxide (NO) and cytokines were determined by reacting cultured medium with griess reagent and enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) were investigated by Western blot and RT-PCR. The anti-oxidant activities of OJS-F increased markedly, in a dose-dependent manner. and, The total phenolic compound and flavonoids contents of OJS-F were 10.20±0.09 ㎍/㎎ and 12.86±0.86 ㎍/㎎. OJS-F which is LPS has diminished in the LPS-induced release of inflammatory mediators (NO, iNOS, COX2 and PGE2) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) from the RAW264.7 macrophages. Therefore, the developed formulation for tablet of ORS-F provide efficiency and usability, and indicated effect of anti-inflammation.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.1
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• pp.33-46
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• 2021

Objectives The aim of this study is to evaluate anti-inflammatory and anti-arthritic effects of Sogyunghwalhyel-tang-gamibang (SGHHTGB) in cell and animal models and also to suggest one of putative mechanisms underlying its anti-arthritic effects. Methods Enzyme-linked immunosorbent assay was applied to measure the concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in culture medium and blood serum and nitric oxide (NO) was assayed by Griess reagent. The expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by Western blot method. Results In a cell model using RAW264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS), the drug, at its non-cytotoxic concentrations, inhibited the production of the pro-inflammatory cytokine TNF-α, IL-1β and IL-6. In addition, it suppressed the expression of the inflammatory enzyme iNOS and COX-2, and reduced the synthesis of the enzyme product NO (as stable nitrite) and PGE2 in activated macrophages. Meanwhile, in an animal model using rheumatic arthritis (RA) mice induced with injection of type II collagen antibody (CAb) and LPS, the drug improved clinical symptom of arthritis and reduced paw thickness and inflammatory cell infiltration. In blood of RA mice, the drug reduced serum levels of TNF-α, IL-1β, IL-6, nitrite, and PGE2, all inflammatory mediators produced by activated macrophages. Conclusions SGHHTGB may ameliorate CAb and LPS-induced RA in mice, presumably by inactivating macrophages that are capable of initiating joint inflammation by producing pro-inflammatory cytokines and expressing inflammatory enzymes.

• Herbal Formula Science
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• v.30 no.2
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• pp.45-57
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• 2022

Objectives : Yukil-san (YIS, 六一散; Liu yi san) is composed of Talcum and Glycyrrhizae Radix, the name is said to be derived from the proportion of the two herbal components of the formula. The YIS originated from 'Formulas from the discussion illuminating the Yellow Emperor's Basic Question'(黃帝素問宣明論方; Huang di su wen xuan ming lun fang) written by Liu Wan-Su (劉完素). YIS could clear summerheat, resolve dampness, and augment the qi. This formula may be used to treat the common cold, influenza, acute gastroenteritis, cystitis, urethritis and bacillary dysentery. But, there is insufficient of study about the effects of YIS on the anti-inflammatory activities. The present study evaluated the anti-inflammatory effects of YIS on lipopolysaccharide (LPS)-activated RAW 264.7 cells. Methods : Cell viability was assessed by MTT assay and nitric oxide (NO) was evaluated by measuring the nitrite content in culture medium. Pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and IL-6 were quantified by ELISA kit. The expression of proteins related with nuclear factor-κB (NF-κB) pathway and inducible NO synthase (iNOS) were assessed by western blot analysis. Results : YIS significantly inhibited the expression of iNOS increased by LPS, and thus significantly inhibited the production of NO. In addition, YIS significantly inhibited pro-inflammatory cytokines. In the regulation of inflammation, NF-κB pathway plays a crucial role. YIS inhibited the expression of p-IκBα and thus inhibited the translocation of NF-κB to the nucleus. Conclusions : These results suggest that YIS ameliorates inflammatory response in LPS-activated RAW 264.7 cells through the inhibition of inflammatory mediators, via suppression of the NF-κB pathway. Therefore, this study provides objective evidence for the anti-inflammatory effect of YIS including the underlying mechanisms.