Zhu Hongkang, Yang Yan, Li Zilin, Wang Xiaoyan, Qian He
State Key Laboratory of Food Science and Technology, Jiangnan University, China.
Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, China.
Food Funct. 2022 Oct 31;13(21):11097-11110. doi: 10.1039/d2fo02308c.
L. has been widely used as an edible, feeding and medicinal plant in the Qinghai-Tibet Plateau due to its several pharmacological effects of alleviating deficiency or weakness, anti-inflammation, and relieving acute mountain sickness. However, its therapeutic efficacy and the underlying mechanism against fatigue have not been elucidated. The aim of this study is to investigate the action mechanisms of L. extract (BE) in treating fatigue, with emphasis on the fatigue-related biomarkers, targets and pathways, network pharmacology and widely targeted metabolomics. Based on the UHPLC-MS results, a total of 33 components were identified and the energy metabolic homeostasis and inflammation related signaling pathways were considered crucial for BE against fatigue by gene functional enrichment analysis. Western blotting (WB) showed that BE significantly up-regulated Nrf2/HO-1, phosphorylation of AMPK, and expression of the downstream signaling pathway, which was further verified by quantitative real-time PCR (q Rt-PCR). The metabolic pathway analysis of BE showed that linoleic acid metabolism was mainly involved, as well as the generation and degradation of ketone bodies, and taurine and hypotaurine metabolism, which are closely related to the regulation of energy metabolism and immunoregulation. Furthermore, the drug-containing serum of BE attenuated intracellular ROS levels in macrophage Raw264.7 cells and reversed the M1 polarization by enhancing the level of IL-10 and Arg-1 and inhibiting that of IL-12 and iNOS . Hence, L. has the potential to become a functional food or alternative therapy for fatigue management among immune-compromised people.
由于具有多种药理作用,如缓解虚损、抗炎和缓解急性高原病等,L. 在青藏高原已被广泛用作食用、饲料和药用植物。然而,其治疗疲劳的疗效及潜在机制尚未阐明。本研究旨在探讨L. 提取物(BE)治疗疲劳的作用机制,重点关注与疲劳相关的生物标志物、靶点和途径、网络药理学及广泛靶向代谢组学。基于超高效液相色谱 - 质谱结果,共鉴定出33种成分,通过基因功能富集分析,能量代谢稳态和炎症相关信号通路被认为对BE抗疲劳至关重要。蛋白质免疫印迹法(WB)显示,BE显著上调Nrf2/HO-1、AMPK磷酸化及下游信号通路的表达,定量实时聚合酶链反应(q Rt-PCR)进一步验证了这一结果。BE的代谢途径分析表明,主要涉及亚油酸代谢以及酮体的生成和降解,还有与能量代谢调节和免疫调节密切相关的牛磺酸和低牛磺酸代谢。此外,BE含药血清可降低巨噬细胞Raw264.7细胞内的活性氧水平,并通过提高IL-10和Arg-1水平、抑制IL-12和iNOS水平来逆转M1极化。因此,L. 有潜力成为免疫功能低下人群疲劳管理的功能性食品或替代疗法。