茯苓皮总三萜抗抑郁作用及机制研究 点击下载
| 论文标题： | 茯苓皮总三萜抗抑郁作用及机制研究 |
| 英文标题： | |
| 中文摘要： | 目的 探讨茯苓皮总三萜（PCTT）的抗抑郁作用及机制。方法采用超高效液相色谱-四极杆飞行时间质谱技术分析PCTT的化学成分。运用网络药理学挖掘PCTT抗抑郁的活性成分、关键靶点及信号通路，并采用分子对接技术验证潜在活性成分和核心靶点的结合能力。动物实验中，分别灌胃80、160、320mg/kg的PCTT14d后，以脂多糖诱导构建小鼠急性抑郁症模型；而后进行行为学测试，检测血清中炎症因子及海马组织中神经递质和脑源性神经营养因子（BDNF）水平，并通过Westernblot法和qPCR法验证PCTT的抗抑郁机制。结果从PCTT中共鉴定出101个化学成分。网络药理学挖掘出10个潜在活性成分（如茯苓酮酸B、茯苓酮酸A、茯苓酸等）、6个核心靶点[如肿瘤坏死因子（TNF）、过氧化物酶体增殖物激活受体、胱天蛋白酶3等]以及TNF、白细胞介素17（IL-17）等多条信号通路。10个潜在活性成分与6个核心靶点均具有较强的结合能力。动物实验结果显示，320mg/kg的PCTT能显著增加模型小鼠的运动距离、运动速度（P＜0.05），缩短悬尾不动时间、游泳不动时间（P＜0.05）；降低血清中IL-6、IL-1β、TNF-α水平，海马组织中谷氨酸水平，前额叶皮质中TNF-α、肿瘤坏死因子受体2（TNFR2）、磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（AKT）mRNA相对表达量以及TNFR2蛋白表达水平和磷酸化PI3K/PI3K、磷酸化AKT/AKT比值；升高海马组织中5-羟色胺、多巴胺、BDNF水平。结论PCTT可能通过调控TNF-α/PI3K/AKT信号通路，下调促炎因子表达，从而调节神经递质及BDNF的释放，进而发挥抗抑郁作用。 |
| 英文摘要： | OBJECTIVE To investigate the antidepressant effect and underlying mechanism of total triterpenes from Poriae Cutis （PCTT）. METHODS UPLC-Q-TOF-MS technology was adopted to analyze the chemical constituents of PCTT. Network pharmacology was applied to screen the antidepressant active ingredients， key targets and signaling pathways of PCTT， and molecular docking was performed to verify the binding capacity between potential active ingredients and core targets. In animal experiment， mice were intragastrically administered PCTT at doses of 80， 160 and 320 mg/kg for 14 consecutive days. Lipopolysaccharide was used to establish an acute depression mouse model. Subsequently， behavioral assays were conducted. The levels of serum inflammatory factors， hippocampal neurotransmitters and brain-derived neurotrophic factor （BDNF） were detected. Western blot and qPCR assays were adopted to validate the antidepressant mechanism of PCTT. RESULTS A total of 101 chemical constituents were identified in PCTT. Network pharmacology screened out 10 potential active ingredients （including poriacosone B， poriacosone A， pachymic acid， etc.）， six core targets [including tumor necrosis factor （TNF）， peroxisome proliferator-activated receptor， caspase-3， etc.]， as well as multiple signaling pathways including TNF and interleukin-17 （IL-17）. All 10 potential active ingredients exhibited strong binding affinity to the six core targets. Animal experimental results demonstrated that 320 mg/kg PCTT markedly increased the movement distance and movement speed of depression model mice （P＜0.05）， and shortened immobility time in tail suspension test and forced swimming test （P＜0.05）. PCTT reduced serum levels of IL-6， IL-1β and TNF-α， decreased hippocampal glutamate level； it also downregulated the relative mRNA expression of TNF-α， tumor necrosis factor receptor-2 （TNFR2）， phosphoinositide 3-kinase （PI3K） and protein kinase B （AKT）， as well as TNFR2 protein expression and the ratios of phosphorylated-PI3K/PI3K，phosphorylated-AKT/AKT in the prefrontal cortex. Meanwhile， PCTT elevated the levels of 5- hydroxytryptamine， dopamine and BDNF in the hippocampus. CONCLUSIONS PCTT exerts antidepressant effects possibly by regulating the TNF-α/PI3K/AKT signaling pathway to downregulate the expression of pro-inflammatory factors， thereby modulating the release of neurotransmitters and BDNF. |
| 期刊： | 2026年第37卷第15期 |
| 作者： | 沈丽；杨玉莹；杨敬宇；沈月；胡鹏；吴雨希；刘丹；叶晓川 |
| 英文作者： | SHEN Li，YANG Yuying，YANG Jingyu，SHEN Yue，HU Peng，WU Yuxi，LIU Dan，YE Xiaochuan |
| 关键字： | 茯苓皮；总三萜；抑郁症；网络药理学；TNF-α/PI3K/AKT信号通路 |
| KEYWORDS： | Poriae Cutis； total triterpenes； depression； |
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