Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Department of Geriatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
J Agric Food Chem. 2022 Jan 12;70(1):184-195. doi: 10.1021/acs.jafc.1c06998. Epub 2022 Jan 4.
The mechanisms of coffee against Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a PD mouse model, then treated with coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of occludin, glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved caspase-3, and cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by 16s rRNA sequencing. Our results showed that coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the MPTP-induced mice. Moreover, coffee increased the level of BBB tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the MPTP-induced mice. Furthermore, coffee significantly decreased the levels of proapoptotic proteins, including Bax, cleaved caspase-3, and cytochrome c, while it increased the level of antiapoptotic protein Bcl-2, consequently preventing MPTP-induced apoptotic cascade. Moreover, coffee improved MPTP-induced gut microbiota dysbiosis. These findings suggested that the neuroprotective effects of coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of coffee on PD.
咖啡防治帕金森病（PD）的机制尚不完全清楚。大量研究表明，肠道微生物群在 PD 的发病机制中起着关键作用。在这里，我们通过调节肠道微生物群来探索咖啡防治 PD 的进一步机制。C57BL/6 小鼠经腹腔注射 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导 PD 小鼠模型，然后连续 4 周给予咖啡治疗。进行杆试验和梁行走试验等行为测试，以评估小鼠的运动功能。评估多巴胺能神经元丢失的酪氨酸羟化酶（TH）和α-突触核蛋白（α-syn）的水平。检测紧密连接蛋白 occludin、胶质纤维酸性蛋白（GFAP）、Bcl-2、Bax、cleaved caspase-3 和细胞色素 c（Cyt c）的水平。此外，通过 16s rRNA 测序测量微生物成分。我们的结果表明，咖啡显著改善了 MPTP 诱导的小鼠的运动障碍和 TH 神经元丢失，并降低了α-syn 的水平。此外，咖啡增加了 BBB 紧密连接蛋白 occludin 的水平，并降低了 MPTP 诱导的小鼠中星形胶质细胞激活标志物 GFAP 的水平。此外，咖啡显著降低了促凋亡蛋白 Bax、cleaved caspase-3 和细胞色素 c 的水平，同时增加了抗凋亡蛋白 Bcl-2 的水平，从而防止了 MPTP 诱导的凋亡级联。此外，咖啡改善了 MPTP 诱导的肠道微生物群失调。这些发现表明，咖啡对 PD 的神经保护作用涉及调节肠道微生物群，这可能为阐明咖啡对 PD 的作用提供新的选择。
