National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China; Joint International Research Laboratory of Food & Medicine Resource Function, Kaifeng, Henan Province, 475004, China.
Zhengzhou City Key Laboratory of Medicinal Resources Research, Huanghe Science and Technology College, Zhengzhou, 450063, China.
Food Chem Toxicol. 2021 Jan;147:111915. doi: 10.1016/j.fct.2020.111915. Epub 2020 Dec 5.
There are few reports on the biological activities of chaetoglobosin V (Cha V) (a cytochalasin alkaloid). In this study, we investigated the molecular mechanisms underlying the anti-inflammatory and antioxidant effects of Cha V in the RAW264.7 cells stimulated lipopolysaccharide (LPS). LPS stimulation-induced oxidative stress (i.e. increase production of reactive oxygen species (ROS) and decreased expression of antioxidant superoxide dismutase (SOD)) was suppressed after a Cha V treatment. Cha V could significantly inhibit the upregulated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene and protein induced by LPS whilst attenuating the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Such antioxidant and anti-inflammatory effects were achieved through the TLR4-mediated MyD88-dependent signaling pathways (via suppressing the phosphorylation of p38, ERK, JNK MAPK and translocation of the NF-κB p65 subunit into nucleus), and the TRIF-dependent signaling pathways (via reducing IFN-β release without inhibiting interferon-regulated factor 3 (IRF3) and IRF7). At 25-100 μM (a concentration range with no cytotoxicity), Cha V dose-dependently influenced SOD enzyme activity and phosphorylation of p38, ERK1/2 and JNK, and at 100 μM, likely exerted the greatest inhibition towards LPS-induced oxidative stress and inflammatory response via the MAPK and NF-κB signaling pathway.
关于 chaetoglobosin V（Cha V）（细胞松弛素生物碱）的生物活性鲜有报道。本研究探讨了 Cha V 在 LPS 刺激的 RAW264.7 细胞中抗炎和抗氧化作用的分子机制。Cha V 处理后，抑制 LPS 刺激诱导的氧化应激（即活性氧（ROS）产生增加和抗氧化超氧化物歧化酶（SOD）表达减少）。Cha V 可显著抑制 LPS 诱导的诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）基因和蛋白的上调表达，同时减弱促炎细胞因子 TNF-α、IL-6 和 IL-1β的产生。这种抗氧化和抗炎作用是通过 TLR4 介导的 MyD88 依赖性信号通路（通过抑制 p38、ERK、JNK MAPK 的磷酸化和 NF-κB p65 亚基向核内易位）和 TRIF 依赖性信号通路（通过减少 IFN-β 的释放而不抑制干扰素调节因子 3（IRF3）和 IRF7）实现的。在 25-100μM（无细胞毒性的浓度范围）时，Cha V 呈浓度依赖性影响 SOD 酶活性和 p38、ERK1/2 和 JNK 的磷酸化，在 100μM 时，通过 MAPK 和 NF-κB 信号通路，可能对 LPS 诱导的氧化应激和炎症反应产生最大的抑制作用。
