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采用网络药理学的方法揭示沉香-陈皮挥发油（CCVO）经吸嗅给药治疗抑郁症的多靶点、多通路机制，并通过分子对接和动物试验进行验证。经过化合物-靶点-通路预测得知化合物1,5-二苯基-1-戊烯-3-酮（A20）和2-(2-苯基)色酮（A21）在网络中起主要作用，GABRA1、CHRM2和GABRA2为核心靶点。通过KEGG通路富集分析得知神经活性配体-受体相互作用通路可能是CCVO治疗抑郁症的关键机制。A20和A21是相互作用网络中的重要成分，且分子对接分数较高，有望成为一种有前景的先导化合物。此外，通过慢性不可预知温和应激（CUMS）模型进行动物试验验证，发现CCVO能显著改善模型大鼠体重、旷场试验、HE染色等指标，蛋白免疫印迹（Western blotting）证实CCVO可显著上调GABRA1、CHRM2和GABRA2的表达，验证了网络药理学对潜在靶点的预测。研究初步解释了CCVO吸嗅给药治疗抑郁症的潜在机制。
Abstract：The method of network pharmacology was employed to elucidate the mechanisms of the compound volatile oil of Aquilaria sinensis(Lour.) Gilg-Citrus reticulata Blanco(CCVO) in treating depressive disorder via inhalation, which involved multiple targets and pathways. The findings were further validated through molecular docking and animal experiments. The compound-target-pathway prediction predicted that 1, 5-diphenyl-1-penten-3-one(A20) and 2-(2-phenylethyl) chromone(A21) played major roles in the network, with GABRA1, CHRM2, and GABRA2 identified as core targets. The neuroactive ligand-receptor interaction pathway might be the key mechanism of CCVO for the treatment of depressive disorder based on KEGG pathway enrichment analysis. A20 and A21 might be promising leading compounds due to the prediction of interaction network and its high molecular docking scores. Moreover, animal experiments were conducted by chronic unpredictable mild stress(CUMS) model, and it confirmed that CCVO could significantly improve the indexes such as weight of model rats, open field test and HE staining. Western blotting analyses confirmed that CCVO could significantly up-regulate the expression of GABRA1, CHRM2 and GABRA2, which verified the previous prediction that these targets might be potential targets for the treatment of depression. In summary, it preliminary explained the potential mechanism of CCVO in the treatment of depressive disorder.
[1]DOBREK L,G?OWACKA K.Depression and its phytopharmacotherapy:a narrative review[J].International Journal of Molecular Sciences,2023,24(5):4772.
[2]YANG F,LODDER P,HUANG N,et al.Thirty-year trends of depressive disorders in 204 countries and territories from 1990to 2019:an age-period-cohort analysis[J].Psychiatry Research,2023,328:115433.
[3]ZHANG S,LU Y J,CHEN W,et al.Network pharmacology and experimental evidence:PI3K/AKT signaling pathway is involved in the antidepressive roles of Chaihu Shugan San[J].Drug Design,Development and Therapy,2021,15:3425-3441.
[4]孙修桥,伍睿昕,楚晓,等.董昌盛运用芳香类中药治疗肺结节规律[J].香料香精化妆品,2024(2):34-40.
[5]ZHANG Y L,LONG Y,YU S,et al.Natural volatile oils derived from herbal medicines:a promising therapy way for treating depressive disorder[J].Pharmacological Research,2021,164:105376.
[6]L?SCHER W,POTSCHKA H.Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases[J].Progress in Neurobiology,2005,76(1):22-76.
[7]ZHAO J Y,LU Y,DU S Y,et al.Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations[J].Journal of Zhejiang University Science B,2012,13(12):990-996.
[8]YUAN T F,SLOTNICK B M.Roles of olfactory system dysfunction in depression[J].Progress in NeuroPsychopharmacology and Biological Psychiatry,2014,54:26-30.
[9]WANG S,WANG C H,YU Z X,et al.Agarwood essential oil ameliorates restrain stress-induced anxiety and depression by inhibiting HPA axis hyperactivity[J].International Journal of Molecular Sciences,2018,19(11):3468.
[10]LI K W,YAN L,ZHANG Y P,et al.Seahorse treatment improves depression-like behavior in mice exposed to CUMSthrough reducing inflammation/oxidants and restoring neurotransmitter and neurotrophin function[J].Journal of Ethnopharmacology,2020,250:112487.
[11]QI Y,CHENG X H,JING H T,et al.Comparative pharmacokinetic study of the components in Alpinia oxyphylla Miq.-Schisandra chinensis (Turcz.) Baill.herb pair and its single herb between normal and Alzheimer,s disease rats by UPLC-MS/MS[J].Journal of Pharmaceutical and Biomedical Analysis,2020,177:112874.
[12]PARK S Y,PARK J H,KIM H S,et al.Systems-level mechanisms of action of Panax ginseng:a network pharmacological approach[J].Journal of Ginseng Research,2018,42(1):98-106.
[13]GUO X,JI J Y,FENG Z T,et al.A network pharmacology approach to explore the potential targets underlying the effect of sinomenine on rheumatoid arthritis[J].International Immunopharmacology,2020,80:106201.
[14]ZHANG Y Q,LIN Y,ZHAO H Y,et al.Revealing the effects of the herbal pair of Euphorbia kansui and Glycyrrhiza on hepatocellular carcinoma ascites with integrating network target analysis and experimental validation[J].International Journal of Biological Sciences,2016,12(5):594-606.
[15]ZHONG Y,ZHENG Q,HU P Y,et al.Sedative and hypnotic effects of compound Anshen essential oil inhalation for insomnia[J].BMC Complementary and Alternative Medicine,2019,19(1):306.
[16]XING H,ZHANG K,ZHANG R W,et al.Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides,Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress[J].Phytomedicine,2015,22(13):1178-1185.
[17]ZHANG L L,YANG Z Y,FAN G,et al.Antidepressant-like effect of Citrus sinensis (L.) osbeck essential oil and its main component limonene on mice[J].Journal of Agricultural and Food Chemistry,2019,67(50):13817-13828.
[18]OKUGAWA H,UEDA R,MATSUMOTO K,et al.Effect of jinkoh-eremol and agarospirol from agarwood on the central nervous system in mice[J].Planta Medica,1996,62(1):2-6.
[19]LIANG Y L,ZHANG X F,ZOU J B,et al.Pharmacology mechanism of Flos magnoliae and Centipeda minima for treating allergic rhinitis based on pharmacology network[J].Drug Development and Industrial Pharmacy,2019,45(9):1547-1555.
[20]ZHANG Y P,YUAN T H,LI Y S,et al.Network pharmacology analysis of the mechanisms of compound herba sarcandrae(Fufang Zhongjiefeng) aerosol in chronic pharyngitis treatment[J].Drug Design,Development and Therapy,2021,15:2783-2803.
[21]LI Q P,HUANG Z W,LIU D F,et al.Effect of berberine on hyperuricemia and kidney injury:a network pharmacology analysis and experimental validation in a mouse model[J].Drug Design,Development and Therapy,2021,15:3241-3254.
[22]LIU J Q,LIU J,TONG X L,et al.Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huai Hua San against ulcerative colitis[J].Drug Design,Development and Therapy,2021,15:3255-3276.
[23]KAO W Y,HSIANG C Y,HO S C,et al.Novel serotoninboosting effect of incense smoke from Kynam agarwood in mice:the involvement of multiple neuroactive pathways[J].Journal of Ethnopharmacology,2021,275:114069.
[24]王艳芳,宋宽,宋昭赫,等.蒙药清心沉香八味散对急性抑郁模型小鼠行为学及单胺类神经递质的影响[J].包头医学院学报,2023,39(11):92-96.
[25]CANNON D M,CARSON R E,NUGENT A C,et al.Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder[J].Archives of General Psychiatry,2006,63(7):741-747.
[26]CANNON D M,KLAVER J K,GANDHI S K,et al.Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder[J].Molecular Psychiatry,2011,16(4):407-418.
[27]HORIUCHI Y,NAKAYAMA J,ISHIGURO H,et al.Possible association between a haplotype of the GABA-a receptor alpha1 subunit gene (GABRA1) and mood disorders[J].Biological Psychiatry,2004,55(1):40-45.
[28]GONZALEZ-NUNEZ V.Role of gabra2,GABAA receptor alpha-2 subunit,in CNS development[J].Biochemistry and Biophysics Reports,2015,3:190-201.
[29]FATEMI S H,FOLSOM T D,ROONEY R J,et al.Expression of GABAA α2-,β1-and ε-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia,major depression and bipolar disorder[J].Translational Psychiatry,2013,3(9):e303.
[30]GODFREY K E M,GARDNER A C,KWON S,et al.Differences in excitatory and inhibitory neurotransmitter levels between depressed patients and healthy controls:a systematic review and meta-analysis[J].Journal of Psychiatric Research,2018,105:33-44.
[31]BAJBOUJ M,LISANBY S H,LANG U E,et al.Evidence for impaired cortical inhibition in patients with unipolar major depression[J].Biological Psychiatry,2006,59(5):395-400.
[32]LEVINSON A J,FITZGERALD P B,FAVALLI G,et al.Evidence of cortical inhibitory deficits in major depressive disorder[J].Biological Psychiatry,2010,67(5):458-464.
[33]DUMAN R S,SANACORA G,KRYSTAL J H.Altered connectivity in depression:GABA and glutamate neurotransmitter deficits and reversal by novel treatments[J].Neuron,2019,102(1):75-90.
[34]FEE C,BANASR M,SIBILLE E.Somatostatin-positive gamma-aminobutyric acid interneuron deficits in depression:cortical microcircuit and therapeutic perspectives[J].Biological Psychiatry,2017,82(8):549-559.
基本信息:
DOI：10.20099/j.issn.1000-4475.2025.0147
中图分类号:R285.5
引用信息:
[1]李慧婷,杨镒,潘登,等.基于网络药理学及CUMS模型研究沉香-陈皮挥发油的抗抑郁作用[J].香料香精化妆品,2025,No.213(06):1-13.DOI:10.20099/j.issn.1000-4475.2025.0147.
基金信息:
海南省重点研发项目（编号ZDYF2025SHFZ055）; 江西省“赣鄱英才”创新领军人才项目（编号S2024LQCQ0477）; 江西省中医药标委会标准化项目（编号2024A023）; 大学生创新创业训练计划项目（编号202410412007、S202410412094）
2025-04-30
2025
2025-07-02
2025
1
2025-12-30
2025-12-30