Xu Jing, Liu Taotao, Pan Fuzhu, Ao Xuan, Wang Lan, Liang Rixin, Lei Yuxin, Ding Yurong, Yu Miao, Li Li, Yang Hongjun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongzhimen NeiNanxiaojie Within 16, Beijing, 100700, China.
Tongjunge Health, Chongqing Taiji Industry (Group) Co. Ltd, Chongqing, 408000, China.
Mol Neurobiol. 2025 Aug;62(8):10228-10244. doi: 10.1007/s12035-025-04865-x. Epub 2025 Apr 7.
Ischemic stroke is a significant public health problem worldwide. Growing evidence has shown gut microbiota served a vital function in ischemic stroke. Rhubarb, always used after processing, is a promising therapy for ischemic stroke. However, the possible mechanism of rhubarb with different cooking methods has remained unclear. Herein, the constitutes of steaming rhubarb (SP), raw rhubarb (RP), and nine steaming nine sun-drying rhubarb (NSP) were identified via LC-QTOF-MS. The middle cerebral artery occlusion (MCAO) mice model was constructed. Infarction area, neurological score, Nissl staining, IBA-1 immunofluorescence, and ELISA were performed to confirm the neuroprotective effect of SP, RP, and NSP. The gut microbiota in fetal was studied via 16sRNA sequencing, and the level of short-chain fatty acids (SCFAs) in brain and gut were measured via GC-MS. The function of microbiota signature was identified through PICRUSt2; the possible mechanism was studied. SP, RP, and NSP alleviated the neurological dysfunction, decreased the inflammation, suppressed dysbiosis of gut microbiota, restored SCFA-producing bacteria, and enhanced the SCFA level in MCAO mice. Moreover, the NSP and SP enriched the proportion of anti-inflammation and beneficial bacteria, deleted the proportion of pro-inflammation. It observed energy metabolism was involved in the possible mechanism of rhubarb; activities of COXI and Na-K-ATPase were increased in the brain of NSP and SP treatment mice. Furthermore, the expression of GLUT4 and PFK1 (the energy metabolism-related genes) was elevated in the brain after RP, NSP and SP administration. In this study, it provided proof for the treatment of ischemic stroke with rhubarb. Rhubarb restored the gut microbiota and regulated the expression of GLUT4 and PFK1 to alleviate ischemic stroke.
缺血性中风是全球范围内一个重大的公共卫生问题。越来越多的证据表明肠道微生物群在缺血性中风中发挥着至关重要的作用。大黄，通常经过炮制后使用，是一种有前景的缺血性中风治疗方法。然而，不同炮制方法的大黄的可能作用机制仍不清楚。在此，通过液相色谱-四极杆飞行时间质谱（LC-QTOF-MS）鉴定了清蒸大黄（SP）、生大黄（RP）和九蒸九晒大黄（NSP）的成分。构建了大脑中动脉闭塞（MCAO）小鼠模型。通过梗死面积、神经功能评分、尼氏染色、离子钙结合衔接分子1（IBA-1）免疫荧光和酶联免疫吸附测定（ELISA）来证实SP、RP和NSP的神经保护作用。通过16sRNA测序研究胎鼠的肠道微生物群，并通过气相色谱-质谱联用（GC-MS）测量大脑和肠道中短链脂肪酸（SCFAs）的水平。通过PICRUSt2鉴定微生物群特征的功能；研究了可能的机制。SP、RP和NSP减轻了MCAO小鼠的神经功能障碍，减轻了炎症，抑制了肠道微生物群的失调，恢复了产生SCFA的细菌，并提高了SCFA水平。此外，NSP和SP增加了抗炎和有益细菌的比例，减少了促炎细菌的比例。观察到能量代谢参与了大黄的可能作用机制；NSP和SP处理小鼠的大脑中细胞色素氧化酶I（COXI）和钠钾ATP酶的活性增加。此外，给予RP、NSP和SP后，大脑中葡萄糖转运蛋白4（GLUT4）和磷酸果糖激酶1（PFK1）（能量代谢相关基因）的表达升高。在本研究中，为大黄治疗缺血性中风提供了证据。大黄恢复了肠道微生物群并调节了GLUT4和PFK1的表达以减轻缺血性中风。
