Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, South Korea; Korean Medicine Research Center for Healthy Aging, Pusan National University, Yangsan, South Korea.
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, South Korea.
Brain Behav Immun. 2021 May;94:410-423. doi: 10.1016/j.bbi.2021.02.028. Epub 2021 Mar 2.
Parkinson's disease (PD) is a neurodegenerative disease involving dopaminergic neuronal death in the substantia nigra (SN); recent studies have shown that interactions between gut and brain play a critical role in the pathogenesis of PD. In this study, the anti-inflammatory effect of Korean red ginseng (KRG) and the changes in gut microbiota were evaluated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Male nine-week-old C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 days. Two hours after the daily MPTP injection, the mice were orally administered 100 mg/kg of KRG, which continued for 7 days beyond the MPTP injections, for a total of 12 consecutive days. Eight days after the final KRG administration, the pole and rotarod tests were performed and brain and colon samples of the mice were collected. Dopaminergic neuronal death, activation of microglia and astrocytes, α-synuclein and expressions of inflammatory cytokines and disruption of tight junction were evaluated. In addition, 16S ribosomal RNA gene sequencing of mouse fecal samples was performed to investigate microbiome changes. KRG treatment prevented MPTP-induced behavioral impairment, dopaminergic neuronal death, activation of microglia and astrocytes in the nigrostriatal pathway, disruption of tight junction and the increase in α-synuclein, interleukin-1β and tumor necrosis factor-α expression in the colon. The 16S rRNA sequencing revealed that MPTP altered the number of bacterial species and their relative abundances, which were partially suppressed by KRG treatment. Especially, KRG suppressed the abundance of the inflammation-related phylum Verrucomicrobia and genera Ruminococcus and Akkermansia (especially Akkermansia muciniphila), and elevated the abundance of Eubacterium, which produces the anti-inflammatory substances. These findings suggest that KRG prevents MPTP-induced dopaminergic neuronal death, activation of microglia and astrocytes, and accumulation of α-synuclein in the SN, and the regulation of inflammation-related factors in the colon may influence the effect.
帕金森病（PD）是一种涉及黑质（SN）中多巴胺能神经元死亡的神经退行性疾病；最近的研究表明，肠道和大脑之间的相互作用在 PD 的发病机制中起着关键作用。在这项研究中，评估了高丽红参（KRG）的抗炎作用和肠道微生物群的变化在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠模型中的作用。雄性 9 周龄 C57BL/6 小鼠每隔 24 小时腹腔注射 30mg/kg 的 MPTP，连续 5 天。每天 MPTP 注射后 2 小时，小鼠口服 100mg/kg 的 KRG，持续 7 天，超过 MPTP 注射，共连续 12 天。最后一次 KRG 给药 8 天后，进行了杆和转棒试验，并收集了小鼠的大脑和结肠样本。评估多巴胺能神经元死亡、小胶质细胞和星形胶质细胞的激活、α-突触核蛋白和炎症细胞因子的表达以及紧密连接的破坏。此外，还对小鼠粪便样本的 16S 核糖体 RNA 基因进行了测序，以研究微生物组的变化。KRG 治疗可预防 MPTP 诱导的行为障碍、黑质纹状体通路中多巴胺能神经元死亡、小胶质细胞和星形胶质细胞的激活、紧密连接的破坏以及α-突触核蛋白、白细胞介素-1β 和肿瘤坏死因子-α 在结肠中的表达增加。16S rRNA 测序显示，MPTP 改变了细菌种类的数量及其相对丰度，而 KRG 治疗部分抑制了这些变化。特别是，KRG 抑制了炎症相关门 Verrucomicrobia 和属 Ruminococcus 和 Akkermansia（特别是 Akkermansia muciniphila）的丰度，并增加了产生抗炎物质的 Eubacterium 的丰度。这些发现表明，KRG 可预防 MPTP 诱导的黑质纹状体通路中多巴胺能神经元死亡、小胶质细胞和星形胶质细胞的激活以及α-突触核蛋白的积累，以及调节结肠中的炎症相关因子可能会影响作用。
