Yao Caihong, Jiang Ning, Sun Xinran, Zhang Yiwen, Pan Ruile, He Qinghu, Chang Qi, Liu Xinmin
Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.
Front Pharmacol. 2024 Nov 1;15:1484337. doi: 10.3389/fphar.2024.1484337. eCollection 2024.
Depression and anxiety are serious psychiatric disorders with significant physical and mental health impacts, necessitating the development of safe and effective treatments. This study aimed to evaluate the efficacy of oligosaccharide (JSO), a type of inulin-based oligosaccharide, in alleviating anxiety and depression and to investigate the underlying molecular mechanisms. Using a mouse model of chronic restraint stress (CRS), JSO was administered orally at doses of 50, 100, and 200 mg/kg for 21 days. Behavioral tests, including the novelty-suppressed feeding test (NSFT), open field test (OFT), elevated plus maze test (EPMT), tail suspension test (TST), and forced swimming test (FST), demonstrated that JSO significantly improved anxiety- and depressive-like behaviors (P< 0.05). Notably, JSO reduced feeding latency in the NSFT, increased time spent in the center in the OFT, enhanced time and entries into open arms in the EPMT, and decreased immobility time in the TST and FST (P< 0.01). Histological and molecular analyses revealed that JSO treatment attenuated neuronal loss in the hippocampus (Hip) and medial prefrontal cortex (mPFC) and reduced the expression of inflammatory markers such as Iba-1 and GFAP in these regions. JSO significantly downregulated the mRNA and protein expression of pro-inflammatory factors (IL-1β, TNF-α, IL-6) while increasing anti-inflammatory markers (IL-10, TGF-β) (P< 0.05). Furthermore, JSO inhibited the c-GAS-STING-NLRP3 axis and apoptosis-related proteins (Bax/Bcl-2, Caspase-3/8/9) while promoting the expression of brain-derived neurotrophic factor (BDNF), PSD-95, and synaptophysin (SYP), indicating improved neuronal survival and synaptic plasticity (P< 0.01). These findings suggest that JSO exerts potent anti-anxiety and antidepressant effects by modulating neuroinflammation, synaptic function, and neuronal apoptosis in the Hip and mPFC of CRS mice. This study highlighted JSO as a potential therapeutic agent for stress-induced anxiety and depression.
抑郁症和焦虑症是严重的精神疾病，对身心健康有重大影响，因此需要开发安全有效的治疗方法。本研究旨在评估一种基于菊粉的低聚糖（JSO）缓解焦虑和抑郁的疗效，并探究其潜在的分子机制。使用慢性束缚应激（CRS）小鼠模型，以50、100和200mg/kg的剂量口服给予JSO，持续21天。行为测试，包括新奇抑制摄食试验（NSFT）、旷场试验（OFT）、高架十字迷宫试验（EPMT）、悬尾试验（TST）和强迫游泳试验（FST），表明JSO显著改善了焦虑样和抑郁样行为（P<0.05）。值得注意的是，JSO缩短了NSFT中的摄食潜伏期，增加了OFT中在中央区域停留的时间，增加了EPMT中进入开放臂的时间和次数，并减少了TST和FST中的不动时间（P<0.01）。组织学和分子分析表明，JSO治疗减轻了海马体（Hip）和内侧前额叶皮质（mPFC）中的神经元损失，并降低了这些区域中炎症标志物如Iba-1和GFAP的表达。JSO显著下调促炎因子（IL-1β、TNF-α、IL-6）的mRNA和蛋白质表达，同时增加抗炎标志物（IL-10、TGF-β）（P<0.05）。此外，JSO抑制c-GAS-STING-NLRP3轴和凋亡相关蛋白（Bax/Bcl-2、Caspase-3/8/9），同时促进脑源性神经营养因子（BDNF）、PSD-95和突触素（SYP）的表达，表明神经元存活和突触可塑性得到改善（P<0.01）。这些发现表明，JSO通过调节CRS小鼠Hip和mPFC中的神经炎症、突触功能和神经元凋亡发挥强大的抗焦虑和抗抑郁作用。本研究强调JSO作为应激诱导的焦虑和抑郁的潜在治疗药物。
