{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:21:34Z","timestamp":1785410494218,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374425"],"award-info":[{"award-number":["82374425"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82374425"],"award-info":[{"award-number":["82374425"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008871","name":"Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["202301AS070053"],"award-info":[{"award-number":["202301AS070053"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Province-Yunnan University of Chinese Medicine Applied Basic Research Joint Special Project","award":["202101AZ070001-034"],"award-info":[{"award-number":["202101AZ070001-034"]}]},{"name":"Yunnan Fundamental Research Project","award":["202301AU070013"],"award-info":[{"award-number":["202301AU070013"]}]},{"name":"Yunnan Fundamental Research Project","award":["202501AT070313"],"award-info":[{"award-number":["202501AT070313"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Cang-ai volatile oil (CAVO) is a traditional Chinese medicine with properties that soothe the liver and alleviate depression. CAVO is widely utilized in the field of antidepressant research and has surfaced as a possible treatment for depression. Depression is a common affective disorder and effective treatment methods are still limited. CAVO is effective in treating depression; however, the exact mechanism is still unclear. This study aimed to explore the likely mechanism by which CAVO reduces symptoms of depression in rats exposed to chronic unpredictable mild stress (CUMS). Methods: We established a CUMS model in Sprague\u2013Dawley rats and administered CAVO via nebulization to evaluate its therapeutic effect. Behavioral and histology tests were conducted to evaluate brain tissue damage. We utilized metabolomics combined with proteomics to analyze the effects of CAVO. We then assessed molecular validation to further clarify the molecular mechanism of its activity. Results: In CUMS model rats, inhaling aerosolized CAVO reduced brain pathology and depression-like behaviors. CAVO changed serum levels of inflammatory cytokines and neurotrophic factors. Biomarkers linked to CAVO\u2019s antidepressant effects were found via metabolomics. Functional analyses highlighted key molecular players such as TrkB, and CREB, and a close association with the antidepressant action of CAVO was confirmed. Conclusions: This study reveals that CAVO reduces depression-like behaviors in CUMS rats by regulating the NT\/Trk signaling pathway. These results demonstrate CAVO\u2019s therapeutic potential and lay the groundwork for future studies and the creation of depressive treatments.<\/jats:p>","DOI":"10.3390\/ph19050751","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cang-Ai Volatile Oil Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-like Symptoms in Rats by Regulating NT\/Trk Signaling Pathway"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9700-1549","authenticated-orcid":false,"given":"Mingqin","family":"Shi","sequence":"first","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"United Graduate School, China Academy of Chinese Medical Sciences, Suzhou 215000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdian","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Qujing University of Medicine & Health Sciences, Qujing 655100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Pan","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"College of Pharmaceutical Science, Dali University, Dali 671000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Qian","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Mengzi, The Affiliated Hospital of Yunnan University of Chinese Medicine, Mengzi 661100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-8408","authenticated-orcid":false,"given":"Dongdong","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev-clinpsy-072220-021440","article-title":"Major Depression and Its Recurrences: Life Course Matters","volume":"18","author":"Monroe","year":"2022","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1001\/jamapsychiatry.2019.4709","article-title":"The Origin of Our Modern Concept of Depression\u2014The History of Melancholia from 1780\u20131880: A Review","volume":"77","author":"Kendler","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/mp.2017.148","article-title":"The genealogy of major depression: Symptoms and signs of melancholia from 1880 to 1900","volume":"22","author":"Kendler","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e879","DOI":"10.1016\/S2214-109X(24)00563-1","article-title":"Data gaps in prevalence rates of mental health conditions around the world: A retrospective analysis of nationally representative data","volume":"13","author":"Casella","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jpsychires.2024.07.054","article-title":"Change in the global burden of depression from 1990\u20132019 and its prediction for 2030","volume":"178","author":"Zhang","year":"2024","journal-title":"J. Psychiatr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-med-051322-120608","article-title":"Ketamine: Mechanisms and Relevance to Treatment of Depression","volume":"75","author":"Kim","year":"2024","journal-title":"Annu. Rev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/wps.21120","article-title":"Treatment-resistant depression: Definition, prevalence, detection, management, and investigational interventions","volume":"22","author":"McIntyre","year":"2023","journal-title":"World Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1017\/S1092852922000906","article-title":"The prescriber\u2019s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression","volume":"28","author":"Abdelmoemin","year":"2023","journal-title":"CNS Spectr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"384","DOI":"10.2174\/1570159X19666210609161447","article-title":"Depression and Pain: Use of Antidepressants","volume":"20","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_11","first-page":"7045","article-title":"The effect of Cangai volatile oil on serum brain-derived neurotrophic factor levels in solitary care combined with chronic stress-induced depression like rats","volume":"37","author":"Cui","year":"2022","journal-title":"Chin. J. Tradit. Chin. Med."},{"key":"ref_12","first-page":"895","article-title":"The effect of Cangai volatile oil regulating TRPC1 signaling pathway on endoplasmic reticulum stress and airway remodeling in asthmatic mice","volume":"56","author":"Wang","year":"2025","journal-title":"Chin. Herb. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112088","DOI":"10.1016\/j.jep.2019.112088","article-title":"Cang-ai volatile oil improves depressive-like behaviors and regulates DA and 5-HT metabolism in the brains of CUMS-induced rats","volume":"244","author":"Chen","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115719","DOI":"10.1016\/j.jep.2022.115719","article-title":"Saffron essential oil ameliorates CUMS-induced depression-like behavior in mice via the MAPK-CREB1-BDNF signaling pathway","volume":"300","author":"Chen","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"149902","DOI":"10.1016\/j.brainres.2025.149902","article-title":"Deep brain stimulation of the olfactory bulb alleviates depressive-like behaviors and alters prefrontal cortex hippocampal coherence","volume":"1866","author":"Bastani","year":"2025","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41398-025-03500-6","article-title":"Modulating salience network connectivity through olfactory nerve stimulation","volume":"15","author":"Heller","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101828","DOI":"10.1016\/j.ctcp.2024.101828","article-title":"Effects of lavender essential oil inhalation aromatherapy on depression and sleep quality in stroke patients: A single-blind randomized controlled trial","volume":"55","author":"Yin","year":"2024","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, Y., Hu, Z., Zhou, K., Wang, Y., Zhang, X., Xue, H., Hu, J., and Wang, J. (2024). The effect of aromatherapy on post-stroke depression: Study protocol for a pilot randomized controlled trial. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1428028"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101973","DOI":"10.1016\/j.ctcp.2025.101973","article-title":"Evaluating the impact of lavender aromatherapy and music therapy on reducing stress, anxiety, and depression in female nurses during the COVID-19 pandemic","volume":"59","author":"Yang","year":"2025","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116835","DOI":"10.1016\/j.biopha.2024.116835","article-title":"Lavender essential oil alleviates depressive-like behavior in alcohol-withdrawn rats: Insights from gut metabolites and hippocampal transcriptome analysis","volume":"176","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Han, L., Wei, S., Wang, R., Liu, Y., Zhong, Y., and Luo, H. (2025). Exploration of the Mechanisms of Acorus tatarinowii in the Treatment of Major Depressive Disorder Based on Network Pharmacology and Molecular Docking Techniques. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47050342"},{"key":"ref_22","first-page":"103797","article-title":"Lithium, a GSK-3\u03b2 inhibitor, attenuates depression and chemobrain induced by doxorubicin in rats: Emphasis on brain BDNF\/TrkB\/Akt\/GSK-3\u03b2\/mTOR\/Nrf2\/HO-1 axis","volume":"393","author":"Elnahas","year":"2025","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178468","DOI":"10.1016\/j.ejphar.2025.178468","article-title":"AdipoRon ameliorates anxiety- and depression-like behaviors in chronic restraint-stressed mice via AMPK-PPAR\u03b1-BDNF-TrkB signaling","volume":"1011","author":"Li","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108047","DOI":"10.1016\/j.phrs.2025.108047","article-title":"Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: A randomised, placebo-controlled, double-blinded clinical trial","volume":"222","author":"Zhang","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/glia.24146","article-title":"Astrocytic p75(NTR) expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption","volume":"70","author":"Qin","year":"2022","journal-title":"Glia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70010","DOI":"10.1111\/jnc.70010","article-title":"Oxidative Stress Suppresses Trk Signaling While Stimulating JNK-Mediated Endocytosis and Cleavage of p75(NTR): A Targetable Pathway for Neuroprotection in a Parkinson\u2019s Disease Model","volume":"169","author":"Pokharel","year":"2025","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40659-024-00504-2","article-title":"Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats","volume":"57","author":"Arenas","year":"2024","journal-title":"Biol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12974-023-02715-y","article-title":"Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy","volume":"20","author":"Yang","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105423","DOI":"10.1016\/j.phrs.2021.105423","article-title":"ERR\u03b3 ligand HPB2 upregulates BDNF-TrkB and enhances dopaminergic neuronal phenotype","volume":"165","author":"Kim","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Turkin, A., Sidorova, M., Kurilova, E., Alenina, N., Tuchina, O., and Klempin, F. (2025). Microglial Expression of Serotonin Receptors Reveals Parallel Regulation of 5-HT2b and BDNF in the Rat Hippocampus. Cells, 15.","DOI":"10.3390\/cells15010066"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Chen, B., Fu, Y., Wan, C., Li, H., Wang, L., Huang, X., Wu, Z., Li, G., and Xiong, L. (2024). Cang-ai volatile oil alleviates nasal inflammation via Th1\/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1332036"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","article-title":"Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability","volume":"99","author":"Antoniuk","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.jad.2020.03.154","article-title":"EZH2 is involved in vulnerability to neuroinflammation and depression-like behaviors induced by chronic stress in different aged mice","volume":"272","author":"Wang","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s12035-025-05325-2","article-title":"Cang-Ai Volatile Oil Mitigates Lipopolysaccharide-Induced Depressive-like Behaviour in Mice by Modulating the Microglial BDNF\/CREB Signaling Pathway","volume":"63","author":"Zhao","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118930","DOI":"10.1016\/j.jep.2024.118930","article-title":"Yiqi Yangxue formula inhibits cartilage degeneration in knee osteoarthritis by regulating LncRNA-UFC1\/miR-34a\/MMP-13 axis","volume":"337","author":"Zhao","year":"2025","journal-title":"J. Ethnopharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:19:28Z","timestamp":1779452368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ph19050751"],"URL":"https:\/\/doi.org\/10.3390\/ph19050751","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]}}}