School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, China.
J Ethnopharmacol. 2021 Oct 28;279:113094. doi: 10.1016/j.jep.2020.113094. Epub 2020 Jul 4.
The husks of Xanthoceras sorbifolia Bunge mainly used in north China as folk medicine were reported to have potential protective effect on cognitive impairment. However, the mechanism remains unclear. In order to fully understand the mechanism of the protection, a complementary study of the husks was conducted.
The urinary and fecal metabolomics were used to analyze the potential biomarkers by the liquid chromatography-tandem time of flight mass spectrometry, and the16S rDNA technology was applied to conduct the analysis of microbiota species in the fecal samples of the rats, which is a significant influencing factor for the development of cognitive impairment.
In metabolomics study, ten potential metabolic biomarkers, which are hippuric acid, kynurenic acid, creatinine, phenylalanine, xanthurenic acid, phenylacetylglycine, succinyladenosine, cresol sulfate, tryptophan 2-C-mannoside and N4-Acetylcytidine in urine, along with two, including isoleucine and phenylalanine in feces, were preliminarily identified, involving multiple pathways such as tryptophan, purine, kynurenine, and phenylalanine metabolism. The perturbation of these metabolic pathways could be related with insulin resistance, oxidative stress, energy metabolism deficit and neuroinflammation, which were risk factors to cause cognitive impairment. In gut microbiota analysis, the relative abundance of c_Bacteroidia, c_Alphaproteobacteria, f_Prevotellaceae, f_Sphingomonadaceae, f_Burkholderiaceae, g_Prevotellaceae_NK3B31_group and p_Bacteroidetes was significantly changed in the rats with cognitive impairment. Spearman's analysis showed obvious correlation between the metabolites and the microbiota species. In the rats with pretreatment of the husks extract, metabolites maintained a relative normal level, and the husks extract could regulate the gut microbiota, especially f_Prevotellaceae and g_Prevotellaceae_NK3B31_group, indicating the effect of the husks on the metabolic pathways via GMs. Such amino acids as isoleucine and phenylalanine failed to show any significant correlation with the microbiota species, indicating that the husks exhibited the potential protective effect through gut microbiota and other pathways.
The husks extract could improve the intestinal microenvironment, and the stability of intestinal microenvironment was associated with normality of tryptophan, purine, kynurenine and phenylalanine metabolic pathways etc, which probably had an effect on cognitive function. This complementary work suggested that gut microbiotas were potential targets of the husks to exert its effect on cognitive impairment.
在中国北方，作为民间药物使用的文冠果壳被报道具有潜在的认知障碍保护作用。然而，其机制尚不清楚。为了充分了解保护机制，对文冠果壳进行了补充研究。
采用液相色谱-串联飞行时间质谱法进行尿和粪便代谢组学分析，应用 16S rDNA 技术对大鼠粪便样本中的微生物群落进行分析，这是导致认知障碍发生的重要影响因素。
在代谢组学研究中，初步鉴定出尿液中 10 种潜在代谢生物标志物，包括马尿酸、犬尿氨酸、肌酸、苯丙氨酸、黄尿酸、苯乙酰甘氨酸、琥珀酰腺苷、甲酚硫酸盐、色氨酸 2-C-甘露糖苷和 N4-乙酰胞苷，粪便中 2 种，包括异亮氨酸和苯丙氨酸，涉及色氨酸、嘌呤、犬尿氨酸和苯丙氨酸代谢等多种途径。这些代谢途径的紊乱可能与胰岛素抵抗、氧化应激、能量代谢不足和神经炎症有关，这些都是导致认知障碍的危险因素。在肠道微生物组分析中，认知障碍大鼠的 c_Bacteroidia、c_Alphaproteobacteria、f_Prevotellaceae、f_Sphingomonadaceae、f_Burkholderiaceae、g_Prevotellaceae_NK3B31_group 和 p_Bacteroidetes 的相对丰度明显发生变化。Spearman 分析显示，代谢物与微生物种类之间存在明显的相关性。在文冠果壳提取物预处理的大鼠中，代谢物保持相对正常水平，文冠果壳提取物可调节肠道微生物群，特别是 f_Prevotellaceae 和 g_Prevotellaceae_NK3B31_group，表明文冠果壳提取物通过 GMs 对代谢途径发挥作用。亮氨酸和苯丙氨酸等氨基酸与微生物种类没有表现出显著相关性，表明文冠果壳提取物通过肠道微生物群和其他途径发挥潜在的保护作用。
文冠果壳提取物可改善肠道微环境，肠道微环境的稳定性与色氨酸、嘌呤、犬尿氨酸和苯丙氨酸代谢途径等的正常性有关，这可能对认知功能有影响。这项补充工作表明，肠道微生物群可能是文冠果壳发挥其对认知障碍作用的潜在靶点。
