中华中医药学刊

基于网络药理学和动物实验验证大枣减附子神经毒性作用机制研究

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陈丽华 , 王萍 , 谢淑鸿 , 吴璐

中华中医药学刊 | 博士导师新论 2026,44(7): 1-7

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中华中医药学刊 |博士导师新论 2026 , 44 (7) : 1 -7

基于网络药理学和动物实验验证大枣减附子神经毒性作用机制研究

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陈丽华（1972-），女，江西崇仁人，教授，博士研究生导师，博士，研究方向：中药新剂型与新技术。

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陈丽华, 王萍, 谢淑鸿, 吴璐

作者信息

江西中医药大学，江西　南昌　330004

通讯作者:

吴璐（1981-），女，湖南长沙人，副教授，硕士，研究方向：中药新剂型、中药传统理论。E-mail：wulu456@126.com。

作者简介:

陈丽华（1972-），女，江西崇仁人，教授，博士研究生导师，博士，研究方向：中药新剂型与新技术。

Investigating Mechanism of Dazao (Ziziphi Jujubae Fructus) in Attenuating Fuzi (Aconiti Lateralis Radix)-Induced Neurotoxicity: A Combined Approach of Network Pharmacology and Animal Experiments

Lihua CHEN, Ping WANG, Shuhong XIE, Lu WU

Affiliations

Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi, China

出版时间: 2026-07-10 doi: 10.13193/j.issn.1673-7717.2026.07.001

文章导航

摘要

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目的

基于网络药理学和动物实验研究大枣减附子神经毒性作用机制。

方法

借助文献检索，通过中药系统药理学数据库与分析平台（Traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）、中药分子机理的生物信息学分析工具（Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine，BATMAN）和本草组鉴（HERB）数据库检索筛选出附子毒性成分和大枣活性成分；用Swiss Target Prediction、PharmMapper数据库预测毒性成分靶点，得到相应成分的靶点库；检索“nerve toxicity”和“toxic encephalopathy”，建立疾病靶点库。然后取成分靶点与疾病靶点的交集，再对两交集靶点进行蛋白质-蛋白质相互作用（Protein-protein interaction，PPI）和京都基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析，实现附子神经毒性网络毒理学分析和大枣减附子神经毒性网络药理学分析，对比所涉及的大枣减毒信号通路与附子神经毒性信号通路，对大枣减毒的潜在作用机制进行预测。以SD大鼠为研究对象，研究附子与大枣配伍前后对大鼠脑组织中超氧化物歧化酶（Superoxide dismutase，SOD）、丙二醛（Malondialdehyde，MDA）的影响，以及对磷脂酰肌醇3激酶（Phosphatidylinositol 3-kinase，PI3K）、蛋白激酶B（Protein kinase B，AKT）和缺氧诱导因子1α（Hypoxia-inducible factor-1α，HIF-1α）mRNA表达水平的影响。

结果

网络药理学整理获得附子潜在毒性成分21个，潜在毒性成分作用靶点1169个，其中神经毒性靶点570个；大枣活性成分29个，收集对应靶点680个，三者取交集得到大枣减附子神经毒性潜在作用靶点76个。PPI网络分析显示，大枣减毒的核心成分为槲皮素、皂苷、生物碱类化合物，KEGG通路分析富集到171条通路，主要涉及PI3K-AKT和HIF-1α等信号通路。动物实验结果显示，附子可导致大鼠脑组织氧化-抗氧化失调，诱发氧化应激，大枣配伍可抑制附子对脑组织的氧化损伤。实时荧光定量聚合酶链式反应（Quantitative real-time polymerase chain reaction，q RT-PCR）实验结果显示，与正常组比较，附子使大鼠脑组织中PI3K、AKT、HIF-1α mRNA水平显著升高，与大枣配伍可使PI3K、AKT、HIF-1α mRNA的表达水平显著下降。

结论

大枣减轻附子神经毒性作用与调控PI3K/AKT/HIF-1信号通路，减轻附子对大鼠脑组织造成的氧化应激损伤有关。研究结果为有毒中药的网络药理学研究提供了新的研究视角，为中药配伍减毒作用机制研究提供了新思路。

关键词

附子 / 大枣 / 神经毒性 / 网络药理学 / 实验验证

Abstract

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Objective

To investigate the mechanism of Dazao (Ziziphi Jujubae Fructus) in reducing Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity based on network pharmacology and animal experiments.

Methods

The toxic components of Fuzi (Aconiti Lateralis Radix) and active constituents of Dazao (Ziziphi Jujubae Fructus) were screened through literature retrieval and database searches. Potential targets of toxic components were predicted using Swiss Target Prediction and PharmMapper databases, followed by construction of a comprehensive target library. A disease target library was established by retrieving “nerve toxicity” and “toxic encephalopathy”-related genes from biomedical databases. The intersection targets between component-related and disease-related targets were subsequently subjected to protein-protein interaction (PPI) network analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Comparative analysis of the identified detoxification pathways [from Dazao (Ziziphi Jujubae Fructus)] and neurotoxicity pathways [from Fuzi (Aconiti Lateralis Radix)] was performed to predict the underlying detoxification mechanisms. Using SD rats as the animal model, a quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate the effects of Fuzi (Aconiti Lateralis Radix) and Dazao (Ziziphi Jujubae Fructus) combination therapy on mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and hypoxia inducible factor-1α(HIF-1α) in the brain tissues of the rats.

Results

Through network pharmacology analysis, it identified 21 potential toxic components and 1169 potential toxic targets in Fuzi (Aconiti Lateralis Radix), including 570 neurotoxic targets. There were 29 active components in Dazao (Ziziphi Jujubae Fructus) with 680 corresponding targets. Venn analysis identified 76 overlapping targets as the potential detoxification targets through which Dazao (Ziziphi Jujubae Fructus) counteracted Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity. PPI network pharmacology identified quercetin, saponins and specific alkaloids as the primary mediators of Dazao (Ziziphi Jujubae Fructus) detoxification effects against Fuzi (Aconiti Lateralis Radix) neurotoxicity. The KEGG pathway analysis identified enrichment in 171 pathways, primarily involving signaling pathways such as the PI3K-AKT signaling pathway and HIF-1 signaling pathway. In vivo studies revealed that Fuzi (Aconiti Lateralis Radix) disrupted redox homeostasis in the rat brain, promoting oxidative stress, whereas co-administration with Dazao (Ziziphi Jujubae Fructus) effectively counteracted these pro-oxidative effects, q RT-PCR experiment results demonstrated that, compared with those of the control group, the mRNA levels of PI3K, AKT and HIF-1α in the cerebral cortex and hippocampal tissues of the rats in the Fuzi (Aconiti Lateralis Radix) group were significantly increased. Compared with those in the Fuzi (Aconiti Lateralis Radix) group, the mRNA expression levels of PI3K, AKT and HIF-1α in the cerebral cortex and hippocampus of rats in the Fuzi (Aconiti Lateralis Radix)-Dazao (Ziziphi Jujubae Fructus) combination group were significantly decreased.

Conclusion

The neuroprotective effect of Dazao (Ziziphi Jujubae Fructus) against Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity is mediated through modulation of the PI3K/AKT/HIF-1 signaling pathway, thereby alleviating Fuzi (Aconiti Lateralis Radix)-triggered oxidative stress damage in rat brain tissues. These findings provide a novel perspective for network pharmacology research on toxic traditional Chinese herbs and offer new insights into the mechanism of toxicity reduction through herbal compatibility.

Key words

Fuzi (Aconiti Lateralis Radix) / Dazao (Ziziphi Jujubae Fructus) / neurotoxicity / network pharmacology / experiment validation

引用本文

陈丽华, 王萍, 谢淑鸿, 吴璐. 基于网络药理学和动物实验验证大枣减附子神经毒性作用机制研究. 中华中医药学刊, 2026 , 44 (7) : 1 -7 . DOI: 10.13193/j.issn.1673-7717.2026.07.001

Lihua CHEN, Ping WANG, Shuhong XIE, Lu WU. Investigating Mechanism of Dazao (Ziziphi Jujubae Fructus) in Attenuating Fuzi (Aconiti Lateralis Radix)-Induced Neurotoxicity: A Combined Approach of Network Pharmacology and Animal Experiments[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (7) : 1 -7 . DOI: 10.13193/j.issn.1673-7717.2026.07.001

基金

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国家自然科学基金项目(82160752)
江西省中医药管理局科技计划项目(2020A0372)
江西省“大学生创新创业训练计划”项目(S202410412061)

参考文献

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2026年第44卷第7期

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doi: 10.13193/j.issn.1673-7717.2026.07.001

首发时间：2026-10-20
出版时间：2026-07-10

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国家自然科学基金项目(82160752)

江西省中医药管理局科技计划项目(2020A0372)

江西省“大学生创新创业训练计划”项目(S202410412061)

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江西中医药大学，江西　南昌　330004

通讯作者:

吴璐（1981-），女，湖南长沙人，副教授，硕士，研究方向：中药新剂型、中药传统理论。E-mail：wulu456@126.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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