Wang Kun, Shen Mengmeng, Tang Hongguang, Zhou Jidong, Liu Yan, Niu Dejun, Zeng Zhen, Pan Lihong, Yao Jingchun, Sun Chenghong
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, 250355, China.
State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, 276005, China.
J Ethnopharmacol. 2025 Jan 31;340:119241. doi: 10.1016/j.jep.2024.119241. Epub 2024 Dec 15.
Chronic fatigue syndrome (CFS), as a complex, multisystemic, and multisystemic disorder affecting multiple organs and systems, often accompanies by symptoms such as post-exercise discomfort, sleep disorders, cognitive difficulties, and orthostatic intolerance. Jingfang Granule (JFG) is a traditional Chinese medicine that have significant protective effects on CFS, but the mechanism is still vague.
This study was designed to evaluate the protective mechanism of JFG on mice with CFS.
The combined stimuli method was used to establish the mice CFS model, and JFG was orally administered. The body weight, exhaustion swimming training and tail suspension test were assayed every 7 days to evaluate the improvement of JFG on CFS. Lactic acid, adenosine triphosphate (ATP), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), IL-1β, TNF-α, IL-6 in serum and liver glycogen, muscle glycogen in muscle were analyzed. Transmission electron microscopy was used to detect mitochondrial morphology. The regulatory networks were investigated by proteomics and central carbon metabolomics, which were verified by Western blot.
JFG reversed the loss of weight and reduce of exhaust swimming time (P < 0.05) induced by CFS in mice, and increased the tail suspension time (P < 0.05), indicating that JFG has an improving effect on CFS. Meanwhile, JFG increased the spleen index (P < 0.05), decreased the thymus index (P < 0.05) and cardiac index (P < 0.05), inhibited the secretion of Lactic acid (P < 0.05), and increased the content of liver glycogen (P < 0.05), muscle glycogen (P < 0.05), and ATP (P < 0.05), and improved mitochondrial morphology in mice with CFS. JFG also inhibited the release of TNF-α (P < 0.05), IL-1β (P < 0.05) and IL-6 (P < 0.05) in serum by inhibiting TLR4/NF-κB signaling pathway and NLRP3 inflammasome signaling pathway, and inhibited oxidative stress by activating Nrf2/HO-1/NQO1 axis. Integrated central carbon metabolomics, proteomics and Western blot showed that JFG intervened in CFS by increasing the expression of Idh1 (P < 0.05) and Idh2 (P < 0.01) to promote tricarboxylic acid (TCA) cycle.
This study confirmed that JFG promoted the TCA cycle by increasing the expression of Idh1 and Idh2, and then inhibited inflammation and oxidative stress to prevent CFS injury, which provided a potential drug candidate for CFS treatment.
慢性疲劳综合征（CFS）是一种影响多个器官和系统的复杂、多系统疾病，常伴有运动后不适、睡眠障碍、认知困难和体位性不耐受等症状。荆防颗粒（JFG）是一种对CFS具有显著保护作用的中药，但其作用机制仍不明确。
本研究旨在评估JFG对CFS小鼠的保护机制。
采用联合刺激法建立小鼠CFS模型，并口服给予JFG。每7天测定体重、疲劳游泳训练和悬尾试验，以评估JFG对CFS的改善作用。分析血清中的乳酸、三磷酸腺苷（ATP）、丙二醛（MDA）、超氧化物歧化酶（SOD）、活性氧（ROS）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）以及肌肉中的肝糖原、肌糖原。采用透射电子显微镜检测线粒体形态。通过蛋白质组学和中心碳代谢组学研究调控网络，并通过蛋白质免疫印迹法进行验证。
JFG可逆转CFS诱导的小鼠体重减轻和疲劳游泳时间缩短（P<0.05），并延长悬尾时间（P<0.05），表明JFG对CFS有改善作用。同时，JFG增加脾脏指数（P<0.05），降低胸腺指数（P<0.05）和心脏指数（P<0.05），抑制乳酸分泌（P<0.05），并增加肝糖原（P<0.05）、肌糖原（P<0.05）和ATP含量（P<0.05），改善CFS小鼠的线粒体形态。JFG还通过抑制TLR4/NF-κB信号通路和NLRP3炎性小体信号通路，抑制血清中TNF-α（P<0.05）、IL-1β（P<0.05）和IL-6（P<0.05）的释放，并通过激活Nrf2/HO-1/NQO1轴抑制氧化应激。综合中心碳代谢组学、蛋白质组学和蛋白质免疫印迹法表明，JFG通过增加异柠檬酸脱氢酶1（Idh1，P<0.05）和异柠檬酸脱氢酶2（Idh2，P<0.01）的表达来促进三羧酸（TCA）循环，从而干预CFS。
本研究证实JFG通过增加Idh1和Idh2的表达促进TCA循环，进而抑制炎症和氧化应激以预防CFS损伤，为CFS治疗提供了一种潜在的候选药物。
