Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
J Ethnopharmacol. 2024 Feb 10;320:117464. doi: 10.1016/j.jep.2023.117464. Epub 2023 Nov 20.
The dried fruit of Schisandra chinensis (Turcz.) Baill (S. chinensis) is widely used in treating central nervous system disorders. Increasing evidence has suggested that alcohol-soluble extracts and lignans from S. chinensis could significantly ameliorate depression-like behaviors in animal models, while there was little research on the potential of alcohol-insoluble polysaccharides as a candidate in the treatment of depression.
Our research was designed to explore both the physicochemical characteristics and antidepressant-like effects of an alcohol-insoluble polysaccharide-rich fraction named SCP from S. chinensis. Simultaneously, the underlying mechanisms were elucidated in the study.
The physicochemical characteristics were accomplished by colorimetric assays, CE, HPGPC, and FT-IR. Behavioral despair testing accompanied by LAT were processed to promptly assess the antidepressant-like effects of SCP in mice. Then OBX-induced mice were established to explore the impacts of chronic co-treatments with SCP. Furthermore, effects of SCP on the HPA axis, oxidant/antioxidant system, neurotrophic and synaptic factors, and gut microbiota in OBX-induced mice were detected through ELISA and 16S rDNA (V3 + V4 regions) gene sequencing.
SCP is a polysaccharide-rich fraction mainly comprised of xylose, glucose, rhamnose, galactose, mannose, and galacturonic acid in ratios of 0.27, 5.09, 0.24, 1.00, 0.63, and 2.86, of which the MW distribution ranges from 681 to 3232 Da. Acute pre-treatment with SCP (200 mg/kg, i.g.) remarkably reduced mice's immobility in the FST without motor stimulation. Prolonged pre-treatments effectively enhanced the effects of SCP on the behavioral despair testing in mice. Chronic co-treatments with SCP (50, 200, and 800 mg/kg, i.g.) could ameliorate the slow increase of body weight and behavioral abnormality of OBX-induced mice in systemic behavioral testing. SCP (200 mg/kg) also successfully restored hyperactivity of the HPA axis, oxidative damage in the liver, neurotrophic disturbance and abnormal synaptic plasticity in the hippocampus, and dysregulation of gut microbiota in OBX-induced mice.
SCP exerts noteworthy antidepressant-like impacts on behavioral despair mice and OBX-induced mice via multiple targets, indicating a potential therapeutic candidate in depression therapy.
五味子(Turcz.)Baill(五味子)的干果实被广泛用于治疗中枢神经系统疾病。越来越多的证据表明,五味子的醇溶性提取物和木脂素可显著改善动物模型中的抑郁样行为,而对于作为候选药物的醇不溶性多糖的潜在作用则研究甚少。
本研究旨在探讨五味子中一种醇不溶性多糖丰富的组分 SCP 的理化特性及其抗抑郁作用。同时,在研究中阐明了其潜在机制。
通过比色法、CE、HPGPC 和 FT-IR 完成了理化特性的测定。采用行为绝望测试(LAT)迅速评估 SCP 对小鼠的抗抑郁样作用。然后建立 OBX 诱导的小鼠模型,以探讨 SCP 与慢性共处理的影响。此外,通过 ELISA 和 16S rDNA(V3+V4 区)基因测序检测 SCP 对 OBX 诱导的小鼠下丘脑-垂体-肾上腺轴(HPA 轴)、氧化应激/抗氧化系统、神经营养和突触因子以及肠道微生物群的影响。
SCP 是一种富含多糖的组分,主要由木糖、葡萄糖、鼠李糖、半乳糖、甘露糖和半乳糖醛酸组成,其比例为 0.27、5.09、0.24、1.00、0.63 和 2.86,其中 MW 分布范围为 681 至 3232Da。急性预给药 SCP(200mg/kg,ig)可显著减少 FST 中小鼠的不动性,而无需运动刺激。长期预处理可有效增强 SCP 对小鼠行为绝望测试的作用。慢性 SCP(50、200 和 800mg/kg,ig)共处理可改善 OBX 诱导的小鼠在全身行为测试中体重缓慢增加和行为异常的情况。SCP(200mg/kg)还成功恢复了 HPA 轴的过度活跃、肝脏的氧化损伤、海马的神经营养障碍和异常的突触可塑性以及 OBX 诱导的小鼠肠道微生物群的失调。
SCP 通过多种靶点对行为绝望小鼠和 OBX 诱导的小鼠产生显著的抗抑郁作用,表明其是治疗抑郁症的潜在治疗候选药物。