Isoliquiritigenin Reduces LPS-Induced Inflammation by Preventing Mitochondrial Fission in BV-2 Microglial Cells
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ORIGINAL ARTICLE
Isoliquiritigenin Reduces LPS-Induced Inflammation by Preventing Mitochondrial Fission in BV-2 Microglial Cells Dong Gil Lee,1 Bo Ra Nam,1 Jae-Won Huh,2 and Dong-Seok Lee
1,3
Received 17 April 2020; accepted 19 October 2020
Abstract— Excessive microglial cell activation in the brain can lead to the production of va-
rious neurotoxic factors (e.g., pro-inflammatory cytokines, nitric oxide) which can, in turn, initiate neurodegenerative processes. Recent research has been reported that mitochondrial dynamics regulate the inflammatory response of lipopolysaccharide (LPS). Isoliquiritigenin (ISL) is a compound found in Glycyrrhizae radix with anti-inflammatory and antioxidant properties. In this study, we investigated the function of ISL on the LPS-induced proinflammatory response in BV-2 microglial cells. We showed that ISL reduced the LPSinduced increase in pro-inflammatory mediators (e.g., nitric oxide and pro-inflammatory cytokines) via the inhibition of ERK/p38/NF-κB activation and the generation of reactive oxygen species (ROS). Furthermore, ISL inhibited the excessive mitochondrial fission induced by LPS, regulating mitochondrial ROS generation and pro-inflammatory response by suppressing the calcium/calcineurin pathway to dephosphorylate Drp1 at the serine 637 residue. Interestingly, the ISL pretreatment reduced the number of apoptotic cells and levels of cleaved caspase3/PARP, compared to LPS-treated cells. Our findings suggested that ISL ameliorated the pro-inflammatory response of microglia by inhibiting dephosphorylation of Drp1 (Ser637)-dependent mitochondrial fission. This study provides the first evidence for the effects of ISL against LPS-induced inflammatory response related and its link to mitochondrial fission and the calcium/calcineurin pathway. Consequently, we also identified the protective effects of ISL against LPS-induced microglial apoptosis, highlighting the pharmacological role of ISL in microglial inflammation-mediated neurodegeneration. Dong Gil Lee and Bo Ra Nam contributed equally to this work. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10753-020-01370-2. 1
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea 2 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Chungcheongbuk-do, Republic of Korea 3 To whom correspondence should be addressed at School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea. E-mail: [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Lee, Nam, Huh, and Lee KEY WORDS: microglia; lipopolysaccharide; isoliquiritigenin; mitochondrial fission; oxidative stress; calcium.
INTRODUCTION Microglia are immune cells found in the human brain, which play an important role in the CNS given their role in neuroprotection [1, 2]. Micr
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