[논문]Carpomitra costata Extract Alleviates Lipopolysaccharide-induced Neuroinflammatory Responses in BV2 Microglia through the Inactivation of NF-κB Associated with the Blockade of the TLR4 Pathway and ROS Generation

Park, Cheol; Cha, Hee-Jae; Hong, Su-Hyun; Kim, Suhkmann; Kim, Heui-Soo; Choi, Yung Hyun

doi:10.15433/ksmb.2020.12.1.029

Carpomitra costata Extract Alleviates Lipopolysaccharide-induced Neuroinflammatory Responses in BV2 Microglia through the Inactivation of NF-κB Associated with the Blockade of the TLR4 Pathway and ROS Generation 원문보기

한국해양바이오학회지 = Journal of marine bioscience and biotechnology, v.12 no.1, 2020년, pp.29 - 39

Park, Cheol (Division of Basic Sciences, College of Liberal Studies, Dong-eui University) , Cha, Hee-Jae (Department of Parasitology and Genetics, Kosin University College of Medicine) , Hong, Su-Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine) , Kim, Suhkmann (Department of Chemistry, College of Natural Sciences, Pusan National University) , Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) , Choi, Yung Hyun (Department of Biochemistry, Dong-eui University College of Korean Medicine)

Abstract ▼ AI-Helper

In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

주제어

표/그림 (6)

그림 Figure 1. Effects of EECC and LPS on the cell viability of BV2 microglial cells.
그림 Figure 2. Suppression of NO and PGE2 production, and iNOS and COX-2 expression by EECC in LPS-stimulated BV2 microglial cells.
그림 Figure 3. Inhibition of the LPS-induced production and expression of pro-inflammatory cytokines by EECC in BV2 microglial cells.
그림 Figure 4. Inhibition of the LPS-induced NF-κB activation by EECC in BV2 microglial cells.
그림 Figure 5. Attenuation of the LPS-induced expression of TLR4 and Myd88, and interaction between LPS and TLR4 by EECC in BV2 microglial cells.
그림 Figure 6. Inhibition of LPS-induced ROS generation by EECC in BV2 microglial cells.

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제안 방법

In this study, we found that EECC can attenuate the onset of the LPS-mediated intracellular signaling pathway by suppressing the activation of NF-κB and inhibiting the binding of LPS to TLR4 in microglial cells.
costata has yet to be clarified. Therefore, this study examined the anti-inflammatory and antioxidant potency of ethanol extract of C. costata (EECC) in BV2 microglia stimulated by LPS and investigated the effect of EECC on the activation of TLR4 signaling pathways by LPS.
To establish the experimental conditions, BV2 cells were treated with a wide range of EECC for 24 h, and cell viability was examined by MTT assay. As shown in Fig.
To investigate the antioxidant potential of EECC, the effect of EECC on LPS-induced ROS production was examined. Our flow cytometry results using the fluorescent probe DCF-DA showed that the level of ROS gradually increased with the treatment of LPS, peaked at 1 h, and decreased thereafter (data not shown).

대상 데이터

EECC used in this study was provided by the National Marine Biodiversity Institute of Korea (Seocheon, Republic of Korea). For the preparation of the EECC, C.

데이터처리

Comparisons between groups were performed by Dunnett’s multiple range tests.

성능/효과

In conclusion, the results obtained in this study demonstrated that EECC had a potent anti-neuroinflammatory effect on BV2 microglial cells. In LPS-stimulated cells, EECC was able to reduce the production of pro-inflammatory mediators and cytokines, which is associated with the decreased expression of their regulatory genes by suppressing NF-κB activity.

후속연구

Furthermore, EECC could block early intracellular signaling cascades by antagonizing against TLR4 or by suppressing ROS accumulation. Although current results may provide a partial understanding of the anti-inflammatory effect of EECC, further studies are needed to assess the major active components of EECC and the mechanical role of EECC in various oxidative stress- and inflammation-mediated diseases.
This antioxidant effect is in line with the current results of EECC, which effectively prevents excessive ROS production. Although the inhibitory effect of EECC on inflammatory response-associated ROS production has been reported for the first time in this study, further studies are needed on the direct link between anti-inflammatory and antioxidant efficacy and the role of intracellular antioxidant systems.

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