Page 52 - 2020年17期

China；2. Dept. of Pharmacy，Sun Yat-sen Memorial Hospital of Sun Yat-sen University，Guangzhou 510120，
China；3. Senior School Section，Shenzhen Middle School，Guangdong Shenzhen 518001，China；4. College of
Chinese Medicine，Guangzhou University of TCM，Guangzhou 510006，China；5. School of Pharmaceutical
Sciences，Guangzhou Medical University，Guangzhou 511436，China）

ABSTRACT OBJECTIVE：To predict the active components and potential target of volatile oil of Citri reticulatae preventing and
treating Alzheimer’s disease （AD）. METHODS：The volatile oil of C. reticulatae was determined by GC-MS，and identified
according to NIST 11.L database and manual data analysis. The active components and targets of volatile oil of C. reticulatae were
predicted through TCMSP and PharmMapper database. The related targets of AD were obtained by using GeneCards and OMIM
databases. Venny 2.1.0 software mapping was used to obtain the direct targets of volatile oil of C. reticulatae against AD. Core
nodes were mined with STRING database and Cytoscape 7.2.1 software，and the indirect targets of volatile oil of C. reticulatae
against AD were obtained by mapping and duplication coith Venny 2.1.0 software. With the help of DAVID 6.7 database，the above
direct and indirect targets（i.e. action targets）were used for gene ontology（GO）function enrichment analysis and KEGG pathway
enrichment analysis. Using Cytoscape 7.2.1 software， topology analysis was conducted for the network of “active
components-acting targets”of volatile oil of C. reticulatae，with node degree value，betweenness centrality and closeness centrality
as indexes，then key components and key targets were mined. RESULTS & CONCLUSIONS：A total of 40 chemical components
in volatile oil were identified by GC-MS，all of them were active components，including D-limonene，γ-terpinene，etc. A total of
151 active components-corresponding targets and 1 291 AD-related targets were mined，including 48 direct targets and 41 indirect
targets. The above 89 targets were mainly concentrated in cell fraction，axon，cytosol and other cell components；intracellular
signaling cascade，response to organic substance and other biological processes；protein kinase activity and amine receptor activity
and other molecular functions；as well as cancer pathway，calcium signaling pathway and neurotrophin signaling pathway（P＜
0.05）. A total of 10 key components including α-terpinene，β-elemen，thymol and（－）-4-terpineol，as well as 21 key targets such
as androgen receptor，prostaglandin G/H synthase 2，mitogen activated protein kinase 14，muscarinic acetylcholine receptor M1
were excavated，indicating the effect of volatile oil of C. reticulatae against AD had the characteristics of multi-component，
multi-target and multi-channel.
KEYWORDS Citri reticulatae；Volatile oil；GC-MS；Network pharmacology；Alzheimer’s disease；Mechanism

青皮为芸香科植物橘（Citrus reticulata Blanco）及其 酯酶抑制剂等化学药物作用靶点单一，且长期服用会引
栽培变种的干燥幼果或未成熟果实的果皮。其中，5～6 发副作用和成瘾性 。因此，多靶点抗 AD 研究已成为
[18]
[19]
月收集自落的幼果晒干者，习称“个青皮”；7～8 月采收 相关药物研发的热门方向 。中药具有丰富的药理活
[4]
未成熟的果实，在果皮上纵剖成四瓣至基部，除尽瓜瓣 性，可通过多通路、多靶点发挥治疗作用 。中药挥发油
[1]
后晒干者，习称“四花青皮”。除橘类未成熟果实的果 是中药材中一种具有挥发性的油状液体，易透过血脑屏
皮外，其同属植物甜橙[C. sinensis（Linn.）Osbeck]、枸橼 障并迅速入脑，具有药理活性丰富、起效靶点多、不良反
（C. medica L.）以 及 茶 枝 柑（C. reticulata Blanco cv. 应较少且症状轻微等特点；同时，其独特的芳香气味容
[18]
Chachiensis）等柑类未成熟果实的果皮在有的地区亦作 易让患者接受并在治疗过程中产生愉悦感 。可见，中
青皮使用 。青皮味辛、苦，性微温，沉降下行，偏于疏肝 药挥发油在防治AD领域中可能具有较大潜力。已有研
[2]
[3]
[20]
胆气分，有破气行痰、消积化滞之功效 ，对心脑血管、消 究显示，罗勒挥发油可抗抑郁 ，石菖蒲挥发油可抗焦
[4]
化系统、呼吸系统 及平滑肌 均具有广泛的药理作用， 虑 ，辛夷、温郁金挥发油可改善实验动物的学习记忆
[21]
[5]
[24]
主要用于治疗肝气郁滞、疝气、胸胁胃脘疼痛、食积、乳 能力 [22-23] ，当归挥发油可提高记忆力、防治 AD 等。有
房胀痛、脘闷嗳气、久疟癖块等症 [6-7] 。青皮挥发油为其 关青皮挥发油防治AD方面的研究主要集中于相关复方
主要药效成分之一，具有理气、调气和抗菌等活性 [8-10] 。 中，如：存注丹可缓解老年人健忘 ，加味癫狂梦醒汤联
[25]
其中，D-柠檬烯是青皮发挥理气作用的主要有效成分， 合盐酸多奈哌齐可更有效地改善AD痰瘀互结证患者的
[15]
[26]
同时还兼具祛痰、抗肿瘤 [11-14] 和广谱抗菌 等作用；对伞 中医证候 。考虑到中药挥发油用于防治情志病具有
花烃、芳樟醇、α-萜品醇以及柠檬醛等是青皮发挥调气 一定的潜力，加之青皮也用于治疗AD的中药复方中，故
[4]
作用的主要成分 ，且α-萜品醇还具有显著的抗菌作 本研究拟探索青皮挥发油防治 AD 的潜在靶点与途径，
[16]
用 。 为进一步阐明复方中单味药的作用机制奠定基础。
阿尔茨海默病（Alzheimer’s disease，AD）是一种中 中药具有多成分、多途径、多靶点的作用特点，其疗
枢神经退行性疾病，也是老年痴呆中较常见的类型之 效通常取决于其中有效成分群的综合作用。网络药理
[17]
一。现有治疗药物的效果欠佳 ，其中常用的乙酰胆碱 学是一种药物设计的新方法，涉及生物信息学、多向药
·2094 · China Pharmacy 2020 Vol. 31 No. 17 中国药房 2020年第31卷第17期