Iwata Yoshika, Miyao Mariko, Hirotsu Akiko, Tatsumi Kenichiro, Matsuyama Tomonori, Uetsuki Nobuo, Tanaka Tomoharu
Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Anesthesia, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-0861, Japan.
Heliyon. 2021 Aug 11;7(8):e07759. doi: 10.1016/j.heliyon.2021.e07759. eCollection 2021 Aug.
Reactive microglia has been associated with neuroinflammation caused by the production of proinflammatory molecules such as cytokines, nitric oxide, and prostaglandins. The overexpression of these molecules may provoke neuronal damage that can cause neurodegenerative diseases. A traditional herbal medicine, Orengedokuto (OGT), has been widely used for treating inflammation-related diseases. However, how it influences neuroinflammation remains poorly understood.
This study investigated the effects of OGT on inflammatory molecule induction in BV-2 microglial cells using real-time RT-PCR and ELISA. An confirmation of these effects was then performed in mice.
OGT showed dose-dependent inhibition of prostaglandin E2 (PGE2) production in BV-2 cells stimulated with lipopolysaccharide (LPS). To elucidate the mechanism of PGE2 inhibition, we examined cyclooxygenases (COXs) and found that OGT did not suppress COX-1 expression or inhibit LPS-induced COX-2 upregulation at either the transcriptional or translational levels. In addition, OGT did not inhibit COX enzyme activities within the concentration that inhibited PGE2 production, suggesting that the effect of OGT is COX-independent. The inhibitory effects of OGT on PGE2 production in BV-2 cells were experimentally replicated in primary cultured astrocytes and mice brains. OGT can be useful in the treatment of neuroinflammatory diseases by modulating PGE2 expression.
反应性小胶质细胞与由细胞因子、一氧化氮和前列腺素等促炎分子产生所引起的神经炎症相关。这些分子的过度表达可能引发神经元损伤，进而导致神经退行性疾病。传统草药黄连解毒汤（OGT）已被广泛用于治疗炎症相关疾病。然而，其如何影响神经炎症仍知之甚少。
本研究使用实时逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）研究了OGT对BV-2小胶质细胞中炎症分子诱导的影响。然后在小鼠中对这些影响进行了验证。
OGT对脂多糖（LPS）刺激的BV-2细胞中前列腺素E2（PGE2）的产生呈现剂量依赖性抑制作用。为阐明PGE2抑制的机制，我们检测了环氧化酶（COXs），发现OGT在转录或翻译水平上均未抑制COX-1的表达或抑制LPS诱导的COX-2上调。此外，在抑制PGE2产生的浓度范围内，OGT并未抑制COX酶的活性，这表明OGT的作用不依赖于COX。OGT对BV-2细胞中PGE2产生的抑制作用在原代培养的星形胶质细胞和小鼠大脑中得到了实验验证。OGT通过调节PGE2表达可能对神经炎症性疾病的治疗有用。
