中国临床药理学杂志

基于BDNF-AKT-mTOR通路探讨百合有效成分的抗抑郁作用及其机制研究

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韦莹莹 ^1a^,² , 邓丽英 ^1b , 陈燕 ^1a , 戴佩如 ^1a , 吴晓梅 ^1a , 陈春林 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(17): 2465-2470

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (17) : 2465 -2470

基于BDNF-AKT-mTOR通路探讨百合有效成分的抗抑郁作用及其机制研究

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韦莹莹^1a^,², 邓丽英^1b, 陈燕^1a, 戴佩如^1a, 吴晓梅^1a, 陈春林^1a

作者信息

^1a.宜春学院，化学与生物工程学院，江西宜春 336000

^1b.宜春学院，医学院，江西宜春 336000

^2.盐城市第三人民医院，药学部，江苏盐城 224000

通讯作者:

陈春林，教授，硕士生导师 MP: 18979539940 E-mail: chenchunlinycxy@ 163.com

作者简介:

韦莹莹（1998-），女，硕士研究生，主要从事神经药理学方面的研究

Research of antidepressant effect and mechanism of effective components of lily based on BDNF-AKT-mTOR pathway

Ying-ying WEI^1a^,², Li-ying DENG^1b, Yan CHEN^1a, Pei-ru DAI^1a, Xiao-mei WU^1a, Chun-lin CHEN^1a

Affiliations

^1a.College of Chemistry and Bioengineering, Yi Chun University, Yichun 336000, Jiangxi Province, China

^1b.College of Medicine, Yi Chun University, Yichun 336000, Jiangxi Province, China

^2.Pharmacy Department, Yancheng Third People’s Hospital, Yancheng 224000, Jiangsu Province, China

出版时间: 2025-09-17 doi: 10.13699/j.cnki.1001-6821.2025.17.012

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摘要

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目的

基于脑源性神经营养因子/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（BDNF/AKT/mTOR）通路探讨百合有效成分的抗抑郁作用及其机制。

方法

在细胞实验中，人神经母细胞瘤细胞（SH-SY5Y）分为空白对照组（细胞培养液）、模型对照组（皮质酮400 μmol·L^-1建模）、百合皂苷低剂量组（皮质酮400 μmol·L^-1+0.2 mg·L^-1百合皂苷）、百合皂苷高剂量组（皮质酮400 μmol·L^-1+0.6 mg·L^-1百合皂苷）、百合多糖低剂量组（皮质酮400 μmol·L^-1+0.2 mg·L^-1百合多糖）和百合多糖高剂量组（皮质酮400 μmol·L^-1+0.6 mg·L^-1百合多糖）。除空白组外，其余各组用皮质酮建立损伤模型，检测细胞存活率。在动物实验中，将48只雄性ICR小鼠随机分成6组：模型组（灌胃等量饮用水）、百合皂苷低剂量组（50 mg·kg^-1）、百合皂苷高剂量组（100 mg·kg^-1）、百合多糖低剂量组（50 mg·kg^-1）、百合多糖高剂量组（100 mg·kg^-1）和阳性药对照组（盐酸氟西汀，10 mg·kg^-1）。各组均给予小鼠急性应激造模，并观察行为学指标变化。用酶联免疫吸附测定法检测血清中皮质酮的水平。用蛋白质免疫印迹分析法检测小鼠前额叶皮层中BDNF/AKT/mTOR信号通路相关蛋白以及突触后致密物95（PSD95）和突触素（Synapsin）的表达水平。

结果

在细胞实验中，模型组、百合皂苷低、高剂量组和百合多糖低、高剂量组的细胞存活率分别是（71.46±1.92）%、（95.97±1.11）%、（105.51±1.80）%、（107.48±0.27）%和（107.66±3.61）%。给药组与模型组存活率相比，在统计学上差异均有统计学意义（均P<0.01）。在动物实验中，模型组和百合皂苷低、高剂量组、百合多糖低、高剂量组和阳性对照组的小鼠悬尾累计不动时间分别是（122.75±4.77）、（90.75±2.09）、（66.13±3.23）、（79.75±2.84）、（54.38±4.40）和（42.00±6.34）s；小鼠血清中皮质酮含量分别是（236.94±6.17）、（213.88±3.95）、（165.52±2.19）、（203.40±3.27）、（170.18±2.18）和（104.96±3.87）ng·mL^-1；脑源性神经营养因子（BDNF）相对表达水平为0.26±0.03、0.74±0.25、0.86±0.03、0.97±0.11、0.92±0.13和1.05±0.23;磷酸化蛋白激酶B/蛋白激酶B（p-AKT/AKT）相对表达水平为0.26±0.03、0.60±0.19、0.75±0.09、0.82±0.05、0.94±0.23和0.58±0.07；磷酸化哺乳动物雷帕霉素靶蛋白/哺乳动物雷帕霉素靶蛋白（p-mTOR/mTOR）相对表达水平为0.46±0.04、0.52±0.19、0.60±0.18、1.01±0.01、0.98±0.06和0.93±0.10；突触后致密物95（PSD95）相对表达水平为0.36±0.05、0.50±0.08、0.60±0.09、0.73±0.09、0.84±0.18和1.00±0.12；突触素（Synapsin）蛋白相对表达水平为0.13±0.04、1.03±0.02、1.16±0.06、1.02±0.00、1.00±0.04和0.65±0.15。高剂量组的上述指标与模型组相比，除高剂量组百合皂苷组的p-mTOR/mTOR和PSD95外，其余各指标在统计学上差异均有统计学意义（P<0.05，P<0.01）。

结论

百合皂苷和多糖可能通过调控BDNF/AKT/mTOR信号通路改善前额叶皮层的突触可塑性，从而改善行为绝望小鼠抑郁样行为，抑制其血清中皮质酮水平。其中百合多糖在改善突触可塑性的效果上略优于百合皂苷。

关键词

百合多糖 / 百合皂苷 / 抑郁 / 急性抑郁模型 / 突触可塑性

Abstract

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Objective

To explore the antidepressant effect and its mechanism of effective components of Lilium brownii based on brain-derived neurotrophic factor/protein kinase B/mammalian target of rapamycin (BDNF/AKT/mTOR) pathway.

Methods

In cellular experiments, the experiments were divided into control group (cell culture solution), model group (corticosterone 400 μmol·L^-1), lily saponin low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy saponin), lily saponin high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy saponin), lily polysaccharide low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy polysaccharide), and lily polysaccharide high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy polysaccharide). Except for the blank group, the remaining groups were modeled with corticosterone to establish human neuroblastoma cells (SH-SY5Y) injury, and cell survival was detected. In the animal experiments, 48 male ICR mice were randomly divided into 6 groups: model group (drinking water with the same amount), low dose of lily saponin (50 mg·kg^-1), high dose of lily saponin (100 mg·kg^-1), low dose of lily polysaccharide (50 mg·kg^-1), high dose of lily polysaccharide (100 mg·kg^-1) and positive drug control group (fluoxetine,10 mg·kg^-1). Each group was given acute stress modeling in mice, and changes in behavioral indexes were observed. Serum corticosterone levels were measured by enzyme-linked immunosorbent assay. The relative expression levels of proteins such as postsynaptic densifier 95 (PSD95) and synapsin in the prefrontal cortex of mice were detected by protein immunoblot analysis.

Results

In the cellular experiments, the cell survival rates of each subgroup were (71.46±1.92)%, (95.97±1.11)%, (105.51±1.80)%, (107.48±0.27)% and (107.66±3.61)%, respectively. The differences between the administered groups and the model group were all statistically significant (all P<0.01). In the animal experiments, the cumulative immobilization time of mice with suspended tails in model group, low and high dose of lily saponin groups, low and high dose of lily polysaccharide group and positive drug group was (122.75±4.77), (90.75±2.09), (66.13±3.23), (79.75±2.84), (54.38±4.40), and (42.00±6.34) s, respectively; the levels of corticosterone in the serum of mice were (236.94±6.17), (213.88±3.95), (165.52±2.19), (203.40±3.27), (170.18±2.18) and (104.96±3.87) ng·mL^-1, respectively; the relative expression levels of brain-derived neurotrophic factor (BDNF) were 0.26±0.03, 0.74±0.25, 0.86±0.03, 0.97±0.11, 0.92±0.13 and 1.05±0.23, respectively; the relative expression levels of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) were 0.26±0.03, 0.60±0.19, 0.75±0.09, 0.82±0.05, 0.94±0.23 and 0.58±0.07, respectively; the relative expression levels of phosphorylated mammalian target of rapamycin/mammalian target of rapamycin protein (p-mTOR/mTOR) were 0.46±0.04, 0.52±0.19, 0.60±0.18, 1.01±0.01, 0.98±0.06 and 0.93±0.10, respectively; the relative expression levels of postsynaptic density protein-95 (PSD95) were 0.36±0.05, 0.50±0.08, 0.60±0.09, 0.73±0.09, 0.84±0.18 and 1.00±0.12, respectively; the relative expression levels of synapsin protein were 0.13±0.04, 1.03±0.02, 1.16±0.06, 1.02±0.00, 1.00±0.04 and 0.65±0.15, respectively. Except the p-mTOR/mTOR and PSD95 in high dose of lily saponin, the differences of the above indexes between the model group and the high dose groups were all statistically significant (P<0.05, P<0.01).

Conclusion

Lily saponins and polysaccharides may improve synaptic plasticity in prefrontal cortex by modulating the BDNF/AKT/mTOR signaling pathway, which improves depressive-like behavior and suppresses serum corticosterone levels in behavioral despair mice. Among them, lily polysaccharides were slightly better than lily saponins in improving synaptic plasticity.

Key words

lily polysaccharide / lily saponin / depression / acute depression model / synaptic plasticity

引用本文

韦莹莹, 邓丽英, 陈燕, 戴佩如, 吴晓梅, 陈春林. 基于BDNF-AKT-mTOR通路探讨百合有效成分的抗抑郁作用及其机制研究. 中国临床药理学杂志, 2025 , 41 (17) : 2465 -2470 . DOI: 10.13699/j.cnki.1001-6821.2025.17.012

Ying-ying WEI, Li-ying DENG, Yan CHEN, Pei-ru DAI, Xiao-mei WU, Chun-lin CHEN. Research of antidepressant effect and mechanism of effective components of lily based on BDNF-AKT-mTOR pathway[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (17) : 2465 -2470 . DOI: 10.13699/j.cnki.1001-6821.2025.17.012

基金

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国家自然科学基金资助项目(81560584)
江西省研究生创新专项基金资助项目(YC2022-s974)

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2025年第41卷第17期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.17.012

接收时间：2024-11-22
首发时间：2026-08-05
出版时间：2025-09-17

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收稿日期：2024-11-22

基金

国家自然科学基金资助项目(81560584)

江西省研究生创新专项基金资助项目(YC2022-s974)

作者信息

^1a.宜春学院，化学与生物工程学院，江西宜春 336000

^1b.宜春学院，医学院，江西宜春 336000

^2.盐城市第三人民医院，药学部，江苏盐城 224000

通讯作者:

陈春林，教授，硕士生导师 MP: 18979539940 E-mail: chenchunlinycxy@ 163.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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