tcm Traditional Chinese Medicine 2166-6059 2166-6067 汉斯出版社 10.12677/tcm.2026.154193 tcm-139100 Article 医药卫生 基于网络药理学与分子对接探讨铁皮石斛 抗疲劳的作用机制 Exploring the Anti-Fatigue Mechanism of Dendrobium officinale Based on Network Pharmacology and Molecular Docking 林 潇 1 王 宗煜 1 许 先源 1 陈 子颜 1 赵 子建 1 杨 汉立 2 段 雪琳 2 广西中医药大学赛恩斯新医药学院，广西 南宁 广西中医药大学壮医药学院，广西 南宁 01 04 2026 04 2026 15 04 143 155 21 01 2026 20 03 2026 07 04 2026 © 2026 Hans Publishers Inc. All rights reserved. 2026 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). https://doi.org/10.12677/tcm.2026.154193

目的：通过网络药理学和分子对接技术探讨铁皮石斛抗疲劳的作用机制。方法：先通过文献挖掘筛选铁皮石斛的活性成分，再借助SwissTargetPrediction数据库获取这些成分的作用靶点；同时利用OMIM、GeneCards、Drugbank数据库挖掘疲劳相关靶点，将两类靶点的交集作为潜在作用靶点开展后续分析。随后采用STRING数据库构建蛋白互作(PPI)网络，通过DAVID数据库进行GO和KEGG通路富集分析，最后运用Cytoscape、Pymol软件完成分子对接。结果：共得到铁皮石斛有效活性成分14个，相关靶点377个，疾病靶点915个，两者共有57个交集。GO功能富集结果显示，“潜在作用靶点”主要涉及胰岛素样生长因子受体信号通路、表皮生长因子受体信号通路等生物过程；细胞质膜、受体复合物等细胞成分；蛋白酪氨酸激酶活性、组蛋白H2AX Y142激酶活性等分子功能。KEGG富集分析显示，潜在作用靶点涉及的通路包括参与癌症中的中央碳代谢、非小细胞肺癌、癌症中的信号通路等。根据分子对接结果可见，潜在作用靶点的蛋白结构与活性成分结合情况良好。结论：铁皮石斛能通过多种途径发挥抗疲劳的功效。

Objective: To investigate the anti-fatigue mechanism of Dendrobium officinale using network pharmacology and molecular docking techniques. Methods: Active components of Dendrobium officinale were searched and screened through literature mining, and their action targets were obtained from the SwissTargetPrediction database. Meanwhile, fatigue-related targets were obtained from the OMIM, GeneCards, and Drugbank databases, and the intersection of the two sets of targets was identified as potential action targets for further analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and GO and KEGG enrichment analyses were conducted using the DAVID database. Finally, molecular docking was performed using Cytoscape and Pymol software. Results: A total of 14 effective active components of Dendrobium officinale were identified, with 377 related targets and 915 disease targets, yielding an intersection of 57. The GO functional enrichment results indicated that the “potential action targets” mainly involve biological processes such as the insulin-like growth factor receptor signaling pathway and epidermal growth factor receptor signaling pathway; cellular components like the cytoplasmic membrane and receptor complex; and molecular functions such as protein tyrosine kinase activity and histone H2AX Y142 kinase activity. The KEGG enrichment analysis indicated that potential targets were associated with pathways including central carbon metabolism in cancer, non-small cell lung cancer, and signaling pathways in cancer. According to molecular docking results, the protein structure of the potential action targets exhibits a good binding situation with the active components. Conclusion: Dendrobium officinale can exert anti-fatigue effects through multiple pathways.

 铁皮石斛 疲劳 网络药理学 分子对接 <i>Dendrobium </i><i>o</i><i>fficinale</i> Fatigue Network Pharmacology Molecular Docking 基金项目 科研立项经费支持 2024年广西中医药大学赛恩斯新医药学院大学生创新训练计划项目(S202413643034)。 1. 引言

人们在持续运动或长期处于压力状态下可能会表现出肌肉酸痛和精神疲惫等疲劳状态。在中医理论中，这种状态多因气血脏腑之间和谐稳定的关系被破坏所致，多种证候均可引发身心压力，最终表现为疲劳[1]。在这种理论指导下，中医提倡通过调和脏腑功能来治标，通过补益气血来治本，双管齐下改善机体疲劳状态，使人体恢复至正常生理状态。

铁皮石斛在很早以前就被誉为滋阴圣药，其功效作用恰好契合了中医在抗疲劳方面的需求。铁皮石斛性味甘淡微寒，在归经上入肺、胃、肾三经，具有清热生津等功效。中医理论体系认为疲劳的核心病机是气阴两虚，而铁皮石斛的滋阴作用则能够很好地抗疲劳[2]。例如，滋养肺阴能够使运动后的一些疲劳状态得到缓解，而补益胃阴则能够加强人体消化吸收功能，从而达到治本的效果。两者相和，具有抗疲劳的作用。现代研究表明，铁皮石斛中含有多种使其能够发挥抗疲劳作用的物质，如多糖、生物碱等。在现代科技的帮助下，铁皮石斛在抗疲劳方面的价值将得到进一步开发[3]。本研究基于网络药理学方法，挖掘铁皮石斛抗疲劳的作用机制，为铁皮石斛药物的开发利用提供新思路。

 2. 材料与方法 2.1. 获取铁皮石斛活性成分及其靶点

利用CNKI检索关键词“铁皮石斛”，收集文献报道中铁皮石斛含有的化学成分。借助SwissADME数据库(http://www.swissadme.ch/)，根据铁皮石斛各成分的化学结构或SMILES字符，预测其成分的ADME参数、药代动力学特性、类药物性质等。以胃肠道吸收(GI-Absorption = high)、类药性(Drug Likeness)中Lipinski、Ghose、Veber、Egan和Muegge是yes的数量 ≥ 3为筛选标准，确定铁皮石斛的主要活性成分。利用SwissTargetPrediction数据平台(http://swisstargetprediction.ch/)，预测铁皮石斛主要活性成分的潜在作用靶点，并以Probability ≥ 0.1为条件进行筛选。

 2.2. 疲劳疾病靶点获取

在GeneCaeds (https://www.genecards.org/)、OMIM (https://www.omim.org/)、Drugbank (https://go.drugbank.com/)数据库查找疲劳的疾病靶点，以Score ≥ 5为条件对GeneCards数据库中靶点进行筛选。

 2.3. 潜在作用靶点获取与活性成分靶点网络构建

在Venny (https://bioinfogp.cnb.csic.es/tools/venny/)中分别导入活性成分和疾病靶点，找到两者交集作为潜在作用靶点。将潜在作用靶点和活性成分导入Cytoscape软件构建活性成分–靶点网络图。

 2.4. 蛋白相互作用网络图(PPI)构建

将潜在作用靶点导入STRING (https://string-db.org/)数据库，物种设为“Homo sapiens”，阈值设为“Medium confidence”，最终将得到的数据导入Cytoscape，并对其进行分析，筛选出Degree值较大的中心基因。

 2.5. GO和KEGG通路富集分析

在DAVID (https://david.ncifcrf.gov/)数据库中检索潜在作用靶点的基因名进行富集分析，包括生物功能(BP)、细胞组分(CC)、分子功能(MF)、KEGG。将分析结果导入微生信平台(https://www.bioinformatics.com.cn/)，对结果进行可视化。

 2.6. 疾病–通路–靶点–成分–药物网络构建

将KEGG分析结果导入Cytoscape对活性成分靶点网络进行补充，构建疾病–通路–靶点–成分–药物网络图，并对其进行分析，筛选出Degree值较大的基因，与中心基因取交集，得到关键基因，用于后续分子对接。

 2.7. 分子对接

选取活性成分–靶点网络中Degree值排名前3的成分与关键基因进行分子对接。在PDB (https://www.rcsb.org/)数据库中下载关键基因对应的蛋白质结构，在TCMSP (https://old.tcmsp-e.com/tcmsp.php)数据库中获取活性成分化学结构。将蛋白结构导入Pymol进行去水和去配体处理，再将基因的蛋白质结构和活性成分化学结构导入AutoDock进行分子对接，最后将对接结果导入Pymol对其进行可视化。

 3. 结果 3.1. 铁皮石斛活性成分及靶点获取

以GI-Absorption = high，以及Drug Likeness中Lipinski、Ghose、Veber、Egan和Muegge是yes的数量 ≥ 3、Probability ≥ 0.1为标准进行筛选，最终得到14个主要活性成分，377个作用靶点。活性成分及靶点信息见表1。

Table 1. Active ingredients of Dendrobium officinale

表1.铁皮石斛活性成分表

活性成分 GI-Absorption 药物靶点/个
毛兰菲 Confusarin high 65
2-羟基柚皮素 2-Hydroxynaringenin high 43
异鼠李素 Isorhamnetin high 100
甘草素 Liquiritigenin high 100
3,3'-二羟基-4,5-二甲氧基联苄基 3,4'-Dihydroxy-4,5-dimethoxybibenzyl high 100
毛兰素 Erianin high 100
滨蒿内酯 Scoparone high 100
升麻素 Cimifugin high 70
南烛木树脂酚 Lyoniresinol high 98
4-烯丙基-2,6-二甲氧基苯基葡萄糖苷 4-allyl-2,6-dimethoxyphenyl glucoside high 57
(+)-丁香脂素 (+)-syringaresinol high 12
柚皮素 Naringenin high 97
对羟基苯甲酸 p-hydroxybenzoic acid high 24
4,4'-二羟基-3,5-二甲氧基联苄 4,4'-dihydroxy-3,5-dimethoxybibenzyl high 100
3.2. 疾病靶点及潜在作用靶点获取

共检索到疲劳相关靶基因971个，其中GeneCards数据库235个、OMIM数据库656个、Drugbank数据库80个，经过汇总去重后得到915个疾病基因。将疾病靶点和白术活性成分靶点导入Venny网站制得韦恩图获得57个交集，并将二者交集确定为潜在作用靶点，见图1。

Figure 1. Key targets of Dendrobium officinale in relation to fatigue

图1.铁皮石斛与疲劳的关键靶点

 3.3. 活性成分靶点网络图

将潜在作用靶点和活性成分导入Cytoscape软件中构建活性成分–靶点网络，见图2。通过AnalyzeNetwork分析网络图，并设置靶点大小与Degree值有关。由图可见，其中Isorhamnetin、Liquiritigenin、Scoparone、3,4'-Dihydroxy-4,5-dimethoxybibenzyl、Erianin、4,4'-dihydroxy-3,5-dimethoxybibenzyl这6个成分的Degree值最大，作用靶点最多，上述成分可能是铁皮石斛抗疲劳的关键成分。

Figure 2. Active component-target network diagram

图2. 活性成分–靶点网络图

 3.4. 蛋白互作网络与中心基因

潜在靶点PPI网络图见图3。在Cytoscape中进行分析后，筛选出个7中心基因，见表2。基因颜色越深，代表Degree值越大，节点越重要。中心基因包括AKT1、EGFR、ALB、ESR1、BCL2、ERBB2、PIK3CA。

Figure 3. Protein-protein interaction (PPI) network diagram of potential targets

图3. 潜在靶点PPI网络图

Table 2. Central genes

表2. 中心基因

序号 基因 Degree 序号 基因 Degree
1 AKT1 39 5 BCL2 31
2 EGFR 33 6 ERBB2 29
3 ALB 32 7 PIK3CA 26
4 ESR1 32
3.5. GO分析图

BP、CC、MF中P值前20的条目见图4。BP包含胰岛素样生长因子受体信号通路(Insulin-Like Growth Factor Receptor Signaling Pathway)、表皮生长因子受体信号通路(Epidermal Growth Factor Receptor Signaling Pathway)等；CC包含细胞质膜(Plasma Membrane)、受体复合物(Receptor Complex)等；MF包含蛋白酪氨酸激酶活性(Protein Tyrosine Kinase Activity)、组蛋白H2AX Y142激酶活性(Histone H2AXY142 Kinase Activity)等。

Figure 4. GO analysis chart

图4. GO分析图

 3.6. KEGG富集分析图

共得到潜在作用靶点参与的通路121条，P值前10的通路见图5 (气泡大小代表基因数量)，包含癌症中的中央碳代谢(Central Carbon Metabolism in Cancer)、非小细胞肺癌(Non-Small Cell Lung Cancer)、癌症中的信号通路(Pathways in Cancer)等。所含基因 > 10的通路名称见表3。

Figure 5. KEGG enrichment analysis chart

图5. KEGG富集分析图

Table 3. KEGG analysis pathways

表3. KEGG分析通路

通路名称 基因数 通路名称 基因数
Pathways in Cancer 24 MicroRNAs in cancer 13
PI3K-Akt Signaling Pathway 20 Melanoma 12
Rap1 Signaling Pathway 15 Breast cancer 12
Central Carbon Metabolism in Cancer 14 Proteoglycans in cancer 12
Ras Signaling Pathway 14 Acute myeloid leukemia 11
Non-Small Cell Lung Cancer 13 Endocrine resistance 11
EGFR Tyrosine Kinase Inhibitor Resistance 13 Gastric cancer 11
Prostate Cancer 13 hsa05207:Chemical carcinogenesis-receptor activation 11
Focal Adhesion 13 cAMP signaling pathway 11
MAPK Signaling Pathway 13 Chemical carcinogenesis-reactive oxygen species 11
3.7. 疾病–通路–靶点–成分–药物网络图

将KEGG分析结果中P值前10的通路及其相关基因补充进活性成分靶点网络图，构建疾病–通路–靶点–成分–药物网络图，见图6。并使用AnalyzeNetwork对其进行分析，选取Degree值前12的基因作为活跃基因，并与中心基因取交集，获得关键基因AKT1、EGFR、PIK3CA。

Figure 6. Disease-pathway-target-component-drug network diagram

图6.疾病–通路–靶点–成分–药物网络图

 3.8. 分子对接结果

活性成分–靶点网络图中Degree值排名前3的活性成分依次为Isorhamnetin、Liquiritigenin、Scoparone，在PPI网络中筛选出的关键基因为AKT1、EGFR、PIK3CA。分子对接结果见表4，选取对接情况较好的3组对其进行可视化，见图7。

Table 4. Molecular docking results

表4.分子对接结果

关键基因 活性成分 结合能
AKT1 Isorhamnetin −2.66
AKT1 Liquiritigenin −4.48
AKT1 Scoparone −3.33
EGFR Isorhamnetin −2.57
EGFR Liquiritigenin −2.93
EGFR Scoparone −3.74
PIK3CA Isorhamnetin −2.51
PIK3CA Liquiritigenin −3.87
PIK3CA Scoparone −2.73

AKT1-Liquiritigenin

PIK3CA-Liquiritigenin

AKT1-Scoparone

Figure 7. Molecular docking

图7. 分子对接

 4. 讨论

通过现代研究可以发现，疲劳的机制涉及多方面，如能量耗竭、代谢产物堆积及氧化应激等，这些因素都有可能导致疲劳[4][5]。本次研究得到了14个铁皮石斛的主要活性成分，其中包括毛兰菲、2-羟基柚皮素、异鼠李素等。将成分靶点和疾病靶点取交集得到了57个潜在作用靶点，然后通过分析潜在作用靶点的PPI网络图得出AKT1、EGFR、ALB、ESR1、BCL2、ERBB2、PIK3CA等基因可能是铁皮石斛发挥抗疲劳作用的主要靶点。根据GO分析的结果可知，在铁皮石斛抗疲劳过程中：生物过程方面，胰岛素样生长因子受体信号通路、表皮生长因子受体信号通路等发挥了重要作用；细胞组分方面，细胞质、受体复合物等信号通路发挥了重要作用；分子功能方面，蛋白酪氨酸激酶活性、组蛋白H2AX Y142激酶活性等信号通路发挥了重要作用。根据KEGG分析的结果可知，在铁皮石斛抗疲劳的过程中，癌症中的中央碳代谢、非小细胞肺癌、癌症中的信号通路等发挥了重要作用。此外，从GO分析和KEGG分析的结果中可以看到，细胞质(Cytoplasm)、癌症中的信号通路(Pathways in Cancer)、内分泌耐药(Endocrine Resistance)有多个关键基因参与。

研究表明，铁皮石斛的活性成分中含有多种黄酮类化合物，如异鼠李素[6]、甘草素[7]、柚皮素[8]、2-羟基柚皮素[9]等均属于黄酮类化合物，在抗氧化方面发挥了重要作用[10]。其中甘草素还能够提高线粒体膜电位，从而改善线粒体功能，提高能量水平，对抗疲劳提供帮助[11]。柚皮素的芳香环上含有抗氧化活性极强的三羟基结构[12]，一方面可减轻小分子淀粉样β蛋白诱导的氧化应激损伤[13]，另一方面能通过下调炎症介导的一氧化氮过量生成，发挥显著的抗氧化作用。上述成分可能在铁皮石斛抗疲劳的过程中发挥了重要的作用[14]。

在PPI网络筛选出的关键基因中，AKT1、EGFR、PIK3CA较为活跃，其中AKT1 (丝氨酸/苏氨酸蛋白激酶B)是AKT激酶家族中重要的一员，又称作蛋白激酶B，是细胞生长和存活过程的关键介质[15]。研究发现，其在细胞凋亡、细胞运动和侵袭以及介导细胞生长增殖等方面有着十分重要的作用[16]。EGFR (表皮生长因子受体)是7号染色体上的一个基因[17]，当EGFR与其它配体结合后，将以同二聚化或异二聚化的方式来激活下游信号通路，并通过PI3K/Akt、Raf/MEK/ERK和JAK/STAT3等胞内信号传导途径调控细胞增殖、分化等生命活动[18]。PIK3CA (磷酸肌醇-3-激酶催化亚基α)是一种编码磷脂酰肌醇3-激酶α (PI3Kα)催化亚基的癌基因[19]-[27]。PI3Kα是一种普遍存在的脂质激酶，可促进细胞生长、增殖和存活，也经常在癌症中发生突变[28]-[31]。GO和KEGG分析的结果显示，细胞质(Cytoplasm)、癌症中的信号通路(Pathways in Cancer)、内分泌耐药(Endocrine Resistance)三个通路中有多个关键基因参与。细胞质(Cytoplasm)是一个在细胞膜和细胞器(包括细胞核)间隙中发生细胞过程的密集而复杂的环境，作为细胞功能的核心，其中会发生大量的化学反应[32]。癌症中的信号通路(Pathways in Cancer)可以通过多种途径来影响机体生命活动，例如促进细胞增殖、迁移、侵袭、炎症、血管生成、细胞凋亡、细胞免疫反应和上皮–间充质转化等[33]。内分泌耐药(Endocrine Resistance)中胰岛素抵抗等过程可能与抗疲劳有关[34]。上述基因和通路可以通过不同途径调控细胞的生命活动，从而影响小鼠体内物质生成与代谢，可能在铁皮石斛抗疲劳的过程中发挥了重要作用。

本次研究通过网络药理学与分子对接相结合的方法说明了铁皮石斛可以通过多靶点、多途径达到抗疲劳的效果。但是本次研究依然存在很大局限：中药成分收集不全面，可能存在部分成分未被收录，以及疾病基因数据滞后等。

 基金项目

2024年广西中医药大学赛恩斯新医药学院大学生创新训练计划项目(S202413643034)。

 NOTES

*通讯作者。

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