Novianti Ela, Katsuura Goro, Kawamura Namiko, Asakawa Akihiro, Inui Akio
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
Research Center for Biotechnology, Indonesian Institute of Sciences, Jl. Raya Bogor Km 46, Jawa Barat, 16911, Indonesia.
Heliyon. 2021 Oct 27;7(10):e08269. doi: 10.1016/j.heliyon.2021.e08269. eCollection 2021 Oct.
Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on the response to lipopolysaccharide (LPS) in mouse microglia and clarified the underlying mechanism. In this study, treatment of MG6 cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of toll-like receptor 4 (TLR4). In addition, pretreatment of MG6 cells and primary cultured microglia cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 induced by LPS (5 ng/mL) without cytotoxicity. Subsequently, pretreatment with AIII significantly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH-terminal kinase (JNK) after LPS stimulation in MG6 cells. These results showed that AIII downregulated TLR4 expression, leading to suppression of the p38 MAPK and JNK pathways, which in turn inhibited the production of pro-inflammatory cytokines and enzymes in LPS-stimulated microglia. Our findings, therefore, suggest the potential for AIII as a therapeutic agent for the treatment of brain inflammation, particularly in microglia-associated inflammation.
白术内酯III（AIII）是从[植物名称]根茎中分离出的一种倍半萜化合物，据报道其在外周器官具有抗炎作用。然而，其对脑内炎症的影响仍不清楚。本研究调查了AIII对小鼠小胶质细胞中脂多糖（LPS）反应的影响，并阐明了潜在机制。在本研究中，用AIII（100μM）处理MG6细胞可显著降低Toll样受体4（TLR4）的mRNA表达和蛋白水平。此外，用AIII（100μM）预处理MG6细胞和原代培养的小胶质细胞，可显著降低LPS（5 ng/mL）诱导的肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、诱导型一氧化氮合酶和环氧化酶-2的mRNA表达和蛋白水平，且无细胞毒性。随后，在MG6细胞中，用AIII预处理可显著抑制LPS刺激后p38丝裂原活化蛋白激酶（p38 MAPK）和c-Jun氨基末端激酶（JNK）的磷酸化。这些结果表明，AIII下调TLR4表达，导致p38 MAPK和JNK信号通路受到抑制，进而抑制LPS刺激的小胶质细胞中促炎细胞因子和酶的产生。因此，我们的研究结果提示AIII作为治疗脑内炎症特别是小胶质细胞相关炎症治疗药物的潜力。
