• BMB Reports
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• v.52 no.10
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• pp.613-618
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• 2019

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.23-43
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• 2010

Objective : This study was performed to assess the effects of Aloe and Violae herba extracts on skin disease and skin beauty. Methods : Anti-oxidant effects were measured by the scavenging for DPPH radical, xanthine oxidase activity. Anti-inflammatory effects were examined by relations in NO synthesis, IL-$1{\beta}$, IL-6, TNF-$\alpha$, NF-kB, COX-2, MAP kinase. The skin wrinkle formation effects were measured by collagenase and elastase activities. The whitening effects were examined by tyrosinase activities, melanin synthesis in MNT-1 cell. Results : 1. In an anti-oxidant test, Aloe and Violae herba extracts showed high radical scavenging activity. 2. In an anti-inflammatory test, Aloe and Violae herba extracts strongly inhibited the lipopolysaccharide(LPS)-induced nitric oxide(NO) release from the RAW 246.7 macrophage cells. Aloe and Violae herba extracts also inhibited the LPS-induced IL-$1{\beta}$ and COX-2 expressions. The inhibitory effects of Aloe and Violae herba extracts on macrophage activation were via the inhibition of NF-kB, evidenced by transient transfection assay. Furthermore, Aloe and Violae herba extracts weakly inhibited the activation of Jun-N-terminal kinase(JNK) but they did not have any effects on p38 MAP kinase in RAW 264.7 cells. 3. In the skin wrinkle formation assay, Aloe extract strongly inhibited collagenase and elastase, whose activity are tightly related with the wrinkle formation. 4. In the skin whitening assay, Aloe and Viloae herba extracts weakly inhibited tyrosinase activity, however, it was not statistically significant. Besides they did not have any effects on melanin synthesis, indicating that they could not be applicable for skin whitening. Conclusion : This study show that Aloe and Violae herba extracts may play a significant role in skin disease and skin beauty.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.757-762
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• 2004

The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes including glutathione S-transferases (GSTs). NF-E2-related factor-2 (Nrf2) phosphorylation by protein kinase C (PKC) is a critical event for its nuclear translocation in response to oxidative stress. Previously, we have shown that peroxynitrite plays a role in activation of Nrf2 and Nrf2 binding to the antioxidant response element (ARE) via the pathway of phosphatidylinositol 3-kinase (PI3-kinase) and that nitric oxide synthase in hepatocytes is required for GSTA2 induction. In view of the importance of PKC and Pl3-kinase in Nrf2-mediated GST induction, we investigated the role of these kinases in peroxynitrite formation for GSTA2 induction by oxidative stress and determined the relationship between PKC and PI3-kinase. Although PKC activation by phorbol 12-myristate-13-acetate (PMA) did not increase the extents of constitutive and inducible GSTA2 expression, either PKC depletion by PMA or PKC inhibition by staurosporine significantly inhibited GSTA2 induction by tert-butylhydroquinone (t-SHa) a prooxidant chemical. Therefore, the basal PKC activity is req- uisite for GSTA2 induction. 3-Morpholinosydnonimine (SIN-1), which decomposes and yields peroxynitrite, induced GSTA2, which was not inhibited by PKC depletion, but slightly enhanced by PKC activation, suggesting that PKC promotes peroxynitrite formation for Nrf2-mediated GSTA2 induction. Treatment of cells with S-nitroso-N-acetyl-penicillamine (SNAP), an exogenous NO donor, in combination with t-BHQ may produce peroxynitrite. GSTA2 induction by SNAP ＋ t-BHQ was not decreased by PKC depletion, but rather enhanced by PKC activation, showing that the activity of PKC might be required for peroxynitrite formation. LY294002 a P13-kinase inhibitor blocked GSTA2 induction by t-BHQ, which was reversed by PMA-induced PKC activation. These results provide evidence that PKC may playa role in formation of peroxynitrite that activates Nrf2 for GSTA2 induction and that PKC may serve an activator for GSTA2 induction downstream of PI3-kinase.

• Journal of Veterinary Science
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• v.22 no.2
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• pp.18.1-18.12
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• 2021

Background: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. Objectives: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. Methods: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O₂^-) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. Results: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O₂^-, and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. Conclusions: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.65-72
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• 2018

The purpose of this study was to investigate probiotic characteristics and immune enhancing effects of Bifidobacterium (B.) longum KBB1-26 and BIF-4, B. breve KBB5-22 isolated from human intestine for probiotic use in humans and animals. We measured acid, bile and heat tolerance, antimicrobial activity against pathogenic bacteria, Escherichia (E.) coli, Salmonella (S.) Enteritidis, Staphylococcus (S.) aureus, and Listeria (L.) monocytogenes. Immune enhancing effects of B. longum and B. breve were investigated by measuring nitric oxide (NO), nuclear factor ($NF-{\kappa}b$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in RAW 264.7 cells or RAW BLUE cells. B. longum KBB1-26 was survived at pH 2.0. B. longum KBB1-26 and BIF-4, B. breve KBB5-22 also showed tolerance to 0.3% of oxgall bile salt. B. longum KBB1-26 was able to survive at $70^{\circ}C$ and $80^{\circ}C$ for 20 min. KBB1-26 showed the antimicrobial inhibition zone to pathogenic bacteria such as E. coli (12 mm), S. Enteritidis (14 mm), S. aureus (14 mm) and L. monocytogenes (41 mm). The production of NO ($4.5{\pm}0.00{\mu}M/mL$) and $IL-1{\beta}$ ($39.7{\pm}0.55pg/mL$) of KBB1-26 significantly higher than BIF-4 and KBB5-22, respectively. In addition, KBB1-26 and KBB5-22 induce the production of high level of $TNF-{\alpha}$ and IL-6 in macrophages. Collectively, B. longum KBB1-26 have acid, bile, heat tolerance, antimicrobial activity and immune enhancing effects. These results suggest that KBB1-26 can be used as probiotics for humans and animals.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.305-311
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• 2018

Osteoarthritis (OA) is the most common form of joint disease, characterized by articular cartilage, osteonecrosis, and osteochondral bone erosion. It is an early, progressive disease that combines joint stiffness and joint pain and reduces cartilage function and condition. Interleukin-1 beta ($IL-1{\beta}$) is thought to be important to the pathogenesis of OA and significantly increases the expression of matrix metalloproteinases (MMPs), which play an important role in cartilage degradation in OA. Sparassis crispa (Wulf.) is an edible / medicinal mushroom that has been reported to variety of biological activities. In this study, investigated the Anti-inflammatory effect of Sparassis crispa (Wulf.) ethanol extract (SCE) on $IL-1{\beta}$ stimulated SW1353 chondrocytes. SCE decreased the expression and activity of MMPs by $IL-1{\beta}$ and decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) associated with the inhibition of prostaglandin E2($PGE_2$) in $IL-1{\beta}$ stimulated SW-1353 chondrocytes. In addition, SCE inhibits the expression of MAPK (mitogen-activated protein kinase) and $NF-{\kappa}B$ (nuclear factor-kappa B) signaling in $IL-1{\beta}$ stimulated SW-1353 cells, and SCE inhibits the production of reactive oxygen species (ROS) through heme oxygenase-1 (HO-1) expression. Thus, it is suggested that SCE has a potential as an anti-inflammatory agent in osteoarthritis treatments.

• BMB Reports
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• v.51 no.12
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• pp.654-659
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• 2018

Antioxidant 1 (ATOX1) protein has been reported to exhibit various protective functions, including antioxidant and chaperone. However, the effects of ATOX1 on the inflammatory response has not been fully elucidated. Thus, we prepared cell permeable Tat-ATOX1 and studied the effects on lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced inflammation. Experimental results showed that transduced Tat-ATOX1 protein significantly suppressed LPS-induced intracellular reactive oxygen species (ROS). Also, Tat-ATOX1 protein markedly inhibited LPS- and TPA-induced inflammatory responses by decreasing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and further inhibited phosphorylation of mitogen activated protein kinases (MAPKs; JNK, ERK and p38) and the nuclear factor-kappaB ($NF-{\kappa}B$) signaling pathway. These results indicate that the Tat-ATOX1 protein has a pivotal role in inflammation via inhibition of inflammatory responses, suggesting Tat-ATOX1 protein may offer a therapeutic strategy for inflammation.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.185-190
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• 2019

Periodontitis is a chronic inflammatory disease and gums pull away from the teeth and form spaces. The main goal of treatment is to control the infection and anti-inflammation. Eucommia ulmoides Oliv. Bark (EU) is a traditional Korean herbal used for the treatment of arthritis and hypertension. In the present study, we investigated the anti-inflammatory properties of EU in Porphyromonas gingivalis-LPS (LPS-PG) induced YD-38 epithelial cells. We observed significant inhibition of nitric oxide (NO) production and the expression of interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor alpha ($TNF-{\alpha}$), cyclooxygenase-2 (COX-2) in LPS-PG-induced YD-38 cells. These results support that EU has an anti-inflammatory effects for the treatment of periodontitis.

• Journal of Applied Biological Chemistry
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• v.62 no.1
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• pp.39-50
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• 2019

Mitogen-activated protein (MAP) kinases play an important role in cell growth and differentiation, as well as the modulation of proinflammatory cytokines. The objective of this study was to examine the increase in the anti-inflammatory effect of Gentiana scabra Bunge (GSB), due to bioconversion with the Aspergillus kawachii crude enzyme, via inhibition of the $NF-{\kappa}B$ signaling and MAP kinase pathways in RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in RAW 264.7 cells treated with the GSB ethyl acetate fraction bioconverted with A. kawachii crude enzyme (GE-BA), was dramatically suppressed as compared to GSB ethyl acetate fraction non-bioconverted with the A. kawachii crude enzyme (GE-UA). The phosphorylation of p38, extracellular signal-regulated kinases, and inhibitory ${\kappa}B$ in RAW 264.7 cells treated with GE-BA was further suppressed, as compared to exposure to GE-UA. Moreover, the mRNA expression of interleukin 6, interleukin 1-beta, and tumor necrosis $factor-{\alpha}$ was further suppressed by GE-BA, compared to GE-UA. Similarly, anti-oxidant activities, such as 2,2-diphenyl-1-picrylhydrazyl hydrate and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity, of GE-BA were further increased compared to GE-UA. These observations demonstrate that the anti-oxidant and anti-inflammatory activities of GSB ethyl acetate fraction increases as a result from bioconversion with the A. kawachii crude enzyme.

• Journal of Acupuncture Research
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• v.36 no.2
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• pp.80-87
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• 2019

Background: This study investigated the anti-inflammatory effects of bee venom (BV) through the inhibition of nuclear factor kappa beta ($NF-{\kappa}B$) expression in macrophages and keratinocytes. Methods: Cell viability assays were performed to investigate the cytotoxicity of BV in activated macrophages [lipopolysaccharide (LPS)] and keratinocytes [interferon-gamma/tumor necrosis factor-alpha ($IFN-{\gamma}/TNF-{\alpha}$)]. A luciferase assay was performed to investigate the cellular expression of $NF-{\kappa}B$ in relation to BV dose. The expression of $NF-{\kappa}B$ inhibitors ($p-I{\kappa}B{\alpha}$, $I{\kappa}B{\alpha}$, and p50 and p65) were determined by Western Blot analysis, and the electromobility shift assay. A nitrite quantification assay was performed to investigate the effect of BV, and $NF-{\kappa}B$ inhibitor on nitric oxide (NO) production in macrophages. In addition, Western Blot analysis was performed to investigate the effect of BV on the expression of mitogen-activated protein kinases (MAPK) in activated macrophages and keratinocytes. Results: BV was not cytotoxic to activated macrophages and keratinocytes. Transcriptional activity of $NF-{\kappa}B$, and p50, p65, and $p-I{\kappa}B{\alpha}$ expression was reduced by treatment with BV in activated macrophages and keratinocytes. Treatment with BV and an $NF-{\kappa}B$ inhibitor, reduced the production of NO by activated macrophages, and also reduced $NF-{\kappa}B$ transcriptional activity in activated keratinocytes (compared with either BV, or $NF-{\kappa}B$ inhibitor treatment). Furthermore, BV decreased p38, p-p38, JNK, and p-JNK expression in LPS-activated macrophages and $IFN-{\gamma}/TNF-{\alpha}$-activated keratinocytes. Conclusion: BV blocked the signaling pathway of $NF-{\kappa}B$, which plays an important role in the inflammatory response in macrophages and keratinocytes. These findings provided the possibility of BV in the treatment of atopic dermatitis.