TLRs are pattern recognition receptors (PRRs) whose cytoplasmic signalling domain is similar to that of IL-1. The extracellular domain of TLRs serve as the binding site of pathogen associated molecular patterns. TLRs are found on both plasma and endosomal membranes and they mainly exert their function by activating genes which lead to production of inflammatory factors. The latest TLR to be discovered, TLR10 is a unique TLR which exhibit anti-inflammatory properties. TLR10 is found on the plasma membrane with other TLRs namely TLR1, TLR2, TLR4, TLR5 and TLR6. Studies have revealed that TLR10 is found on the same gene cluster with TLR1 and TLR6 and is also a coreceptor of TLR2. Up to date, TLR10 is the only TLR which exhibit anti-inflammatory property. Previously, TLR10 was thought to be an "orphan receptor" but much recent studies have identified ligands for TLR10. Currently there is no review article on TLR10 that has been published. In this narrative review, we are going to give an account of TLR10, its functions mainly as an anti-inflammatory PRR and its possible applications as a target in therapeutics.
Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2',3'-dihydroxy or 3',4'-dihydroxy or 3',4'-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2',3',5,7-tet-rahydroxyflavone and 3',4',5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.
Lee, Ba Wool;Park, Il-Ho;Yim, Dongsool;Choi, Sung Sook
Natural Product Sciences
/
v.23
no.1
/
pp.46-52
/
2017
The aim of this study was to evaluate the anti-Helicobacter pylori activity of fractions and major aglycon compounds (baicalein, chrysin, oroxylin A, wogonin) of Scutellariae Radix. Minimum inhibitory concentration (MIC) measurement, DPPH radical-scavenging assay, DNA protection assay, and urease inhibition analysis were performed. The ethyl acetate (EtOAc) fraction showed the potent anti-Helicobacter activity, and therefore, compounds in the EtOAc fraction were subjected to further assay. The MICs of chrysin, oroxylin A, and wogonin against Helicobacter pylori 26695 were 6.25, 12.5 and $25{\mu}g/mL$, respectively. Baicalein exhibited the most effective DPPH radical-scavenging activity. DNA protection using Fenton reaction, chrysin, oroxylin A, and wogonin showed effective DNA protective effect. This result was also confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Regarding Jack bean urease (0.5 mg/mL, 50 unit/mg) inhibition, 20 mM ofbaicalein and chrysin inhibited urease activity by 88.2% and 72.5%, respectively.
Son, Ji Yoon;Park, Young W.;Renchinkhand, Gereltuya;Han, Jung Pil;Bum, Jin Woo;Paik, Seung-Hee;Lee, Jo Yoon;Nam, Myoung Soo
Journal of Life Science
/
v.26
no.6
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pp.689-697
/
2016
Kefir is an acidic-alcoholic fermented milk product originating from the Caucasian mountains. Kefir has long been known for its probiotic health benefits, including its immunomodulatory effects. The objectives of this study were to investigate the properties of a fermented whey product and to examine the effects of kefir grains on the in vitro immune-modulation of human mast cell-1 (HMC-1). The results showed that the whey fermented by kefir grains contained the maximum lactic acid bacteria and yeast for 16 hr by 1.83×108 and 6.5×105 CFU/ml, respectively, and lactose and whey proteins were partially hydrolyzed. The experimental whey fermented by kefir grains exhibited an in vitro anti-inflammatory effect on the HMC-1 line for 8, 16, and 24 hr, and this effect induced the expression of interleukin (IL)-4 as a pro-inflammatory cytokine, but not for 48 hr by RT-PCR in HMC-1 cells. In addition, the same phenomenon was observed for the expression of IL-8 as a pro-inflammatory cytokine by the kefir-fermented whey during the same periods of 8-48 hr under the same conditions. These cytokines resulted in the production of IL-4 at 20-25 ng in HMC-1 cells for 8, 16, and 24 hr, whereas 5 ng was produced for 48 hr by the fermented whey. In contrast, IL-8 was produced at 15-20 ng in HMC-1 cells during 4, 8, 16, and 24 hr, while 7 ng was produced at 48 hr. It was concluded that the whey fermented by kefir grains possesses a potential anti-inflammatory function, which could be used for an industrial application as an ingredient of functional foods and pharmaceutical products.
Park, Mi-Jeong;Park, Hye-Jin;Lee, Eun-Ho;Jung, Hee-Young;Cho, Young-Je
Journal of Applied Biological Chemistry
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v.61
no.2
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pp.141-150
/
2018
In this study, the inflammation of ethanol extracts from Caryopteris incana (CI) and fermented C. incana (FCI) on induced to lipopolysaccharide with Raw 264.7 cell was tested. The composition profile of L. plantarum was changed by fermentation, and confirmed by HPLC analysis. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyltetrazolium bromide assay to evaluate the toxicity of CI and FCI extracts. In cell viability, cell toxicity was not shown at 5, 10 and $15{\mu}g/mL$ of CI extracts and 10, 20, 30 and $40{\mu}g/mL$ of FCI extracts. The results of inducible nitric oxide synthase and cyclooxygenase-2 protein production were confirmed to be inhibitory in a concentration-dependent manner, respectively. Additionally, protein expression of nitric oxide and prostaglandin $E_2$ by CI and FCI extracts were also inhibited in a concentration-dependent manner. In the result of pro-inflammatory cytokine, $15{\mu}g/mL$ concentration of CI extracts was showed tumar necrosis factor $(TNF)-{\alpha}$ (57.3%), interleukin (IL)-6 (35.2%), and $IL-1{\beta}$ (48.0%), respectively. And $40{\mu}g/mL$ of FCI extracts was showed $TNF-{\alpha}$ (34.6%), IL-6 (32.1%), and $IL-1{\beta}$ (30.0%), respectively. These results suggest that FCI extracts showed better effect of anti-inflammatory than CI extracts. Therefore, it was found that both CI and FCI can be used as an excellent material for the development of new anti-inflammatory resource.
This study was performed to define the cytotoxicity and the anti-inflammatory action of Pulsatilla koreana extracts. To analyze cytotoxic effects, gingival and periodontal ligament fibroblasts were used, and anti-inflammatory actions related to reduction of $IL-1{\beta}$ and $PGE_2$ production were performed in vitro, for the suggestion of efficacy and safety on periodontal therapeutic use of Pulsatilla koreana extracts. We extracted ethylacetate and butylalcohol from well-dried and ground Pulsatilla koreana throughout multiple processing, then used different concentration solution(0.1 %, 0.2 %, 0.4 %, 0.01 %, 0.02 %, 0.04 %, 1 %, 2 %) of ethylacetate and butylalcohol extracts to examine eytotoxic effects and anti-inflammatory actions Cytotoxic effects were examined by ELISA reader using MTT(Methyl Thiazol-2-YL-2, 5-diphenyl Tetrazolium bromide)solution following culture of human gingival and periodontal ligament fibroblasts. Synthesis of $IL-1{\beta}$was examined by $IL-1{\beta}$ enzyme-immunoassay(EIA)system after separation and culture of monocyte, and $PGE_2$ was examined by $PGE_2EIA$ system after culture of gingival fibroblasts. The results were as follows: 1. In the MTT test of gingival fibroblasts, the change of optical density was decreased significantly at 2 % of butylalcohol extracts and 0.04 %, 0.1 %, 0.2 %, 0.4 %, 1 %, 2 % of ethylacetate extracts.(p<0.05) 2. In the MTT test of periodontal ligament cells, the change of optical density were not differ significantly. but butylalcohol and ethylacetate extracts except from butylalcohol 0.01 % showed high cell cytotoxity. 3. Both ethylacetate and butylalcohol extracts from Pulsatilla koreana inhibited the synthesis of $IL-1{\beta}$and inhibition effect of ethylacetate extracts were higher than butylalcohol extracts. 4. Both ethylacetate and butylalcohol extracts from Pulsatilla koreana inhibited the synthesis of $PGE_2$, and ethylacetate extracts were higher than butylalcohol extracts. In conclusion, ethylacetate and butylalcohol extracts from Pulsatilla koreana showed little cell cytotoxity for gingival and periodontal ligament fibroblasts, and the inhibition of $IL-1{\beta}$ and $PGE_2$ sysnthesis, therefore it is considered that these extracts can be developed as the therapeutics of the periodontal disease.
Lee, Hae Jin;Sim, Boo Yong;Bak, Ji Won;Kim, Dong Hee
Journal of Physiology & Pathology in Korean Medicine
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v.28
no.2
/
pp.146-153
/
2014
Gami-Sopungsan (GS) is one of the traditional korean remedy. We investigated the anti-inflammation and anti-atopic dermatitis (AD) effect of GS. No cytotoxicity of GS was observed in the range of $1{\sim}100{\mu}g/m{\ell}$ on Raw 264.7 cells. The Inflammatory response of Raw 264.7 cells were induced by lipopolysaccharide (LPS), followed by GS treatment at indicated concentrations (0, 1, 10 and $100{\mu}g/m{\ell}$). At $100{\mu}g/m{\ell}$ concentration, GS showed inhibitory effect on LPS-induced nitric oxide production by 20%. Production of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ was decreased by approximately 56%, 36% and 79%, respectively upon GS treatment at $100{\mu}g/m{\ell}$. 200 mg/kg of GS was orally administered to NC/Nga mice, where AD was induced by 1-chloro 2,4-dinitrobenzene. There were no significant difference between GS treated group and the control group on body weight and food intake changes during growth. The back skin of GS group showed decrease in erythema, pruritus, dry skin, edema, excoriation, erosion and lichenification level through naked eye observations. In addition, leukocyte infiltration and the thickness of epidermis were significantly decreased in the skin tissues (back and ear). The serum IgE levels were decreased by 28.8% in the GS treated group. The GS treated group showed remarkable inhibition of IL-4 (83%), IL-5 (95%), IL-6 (62%) and TNF-${\alpha}$ (84%) in serum, indicating that GS has similar or higher efficacy than those of the dexamethasone treated group. From the results above, we conclude that GS has significant anti-inflammation and anti-AD effects on Raw 264.7 cells and NC/Nga mice. The results should provide fundamental and valuable data for the research on natural products being developed against atopic dermatitis.
Kim, Sang Suk;Park, Kyung Jin;Lee, Seung Eun;Lee, Jeong Hoon;Choi, Young Hun
Food Science and Preservation
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v.24
no.6
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pp.842-848
/
2017
Hylotelephium erythrostictum is commonly used as a medicinal herb. In this study, H. erythrostictum leaf (HEL), branch (HEB), root (HER), and above ground (HEAG) extracts were evaluated for their antioxidant properties. The antioxidant activities were assayed by three methods based on scavenging of DPPH, ABTS and superoxide anion radical. HEAG extract showed the highest DPPH, ABTS, superoxide anion radical scavenging activities. HEAG extract also exhibited the highest phenolic content (230 mg/g gallic acid equivalent). In our research for anti-inflammatory ingredients, the extract of HEAG inhibited the generation of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. To test the inhibitory effects of HEAG on pro-inflammatory cytokines, we conducted ELISA assay for the measuring the generation of tumor necrosis factor $(TNF)-{\alpha}$, IL (interleukin)-$1{\beta}$, and IL(interleukin)-6 in LPS-stimulated RAW264.7 macrophage cells. In these assays, HEAG ethanol extract showed a dose-dependent decrease in the production of $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6. Based on these results, extract of HEAG could be the efficient candidate for anti-inflammatory agents.
Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.
Song-in Kim;Eunbee Cho;Kyohee Cho;Chang Kwon;Seok-hee Lim;Jong Won Kim;Myung Jun Chung;Su Jeong Kim;Sanghyun Lim
Microbiology and Biotechnology Letters
/
v.51
no.4
/
pp.465-473
/
2023
In this study, we aimed to evaluate the bioconversion ability of single (Lactiplantibacillus plantarum CBT LP3, Lactococcus lactis subsp. lactis CBT SL6, Streptococcus thermophilus CBT ST3) and multi-strain probiotics to convert rutin to quercetin in roasted tartary buckwheat, and to assess their biological activities. To evaluate the bioconversion efficiency, each strain was cultured for 24 h in MRS media with 5% roasted tartary buckwheat 'Hwangguem-Miso' powder. After then, rutin and quercetin contents were determined by HPLC. Additionally, the biological activities were compared before and after bioconversion of an ingredient. Anti-oxidant effects were measured by DPPH and ABTS assays. Anti-inflammatory effects were determined by measuring NO production, and levels of iNOS, TNF-α, IL-6 and IL-4 using an LPS-induced Raw 264.7 cell model. The bioconversion rate under the combination of three species of probiotics significantly increased more than single species. Antioxidant efficacy results showed the highest activity when the combination of three species of probiotics cultured. The pro-inflammatory factors such as nitric oxide, iNOS, TNF-a, and IL-6 were significantly decreased when the three types of probiotics were combined than single strain was cultured. In addition, level in the anti-inflammatory factor IL-4 was increased. The multi-strain probiotics showed increased bioconversion efficiency, effects of anti-oxidant and anti-inflammatory compared to the single strain. These findings suggest that the fermentation of tartary buckwheat by probiotics may be a valuable candidate for developing functional foods with anti-oxidation and anti-inflammation.
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