{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:57:56Z","timestamp":1791496676043,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}]},{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}]},{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}]},{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["82204657"],"award-info":[{"award-number":["82204657"]}]},{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}]},{"name":"Hainan International Science and Technology Cooperation Research and Development Project","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["82204657"],"award-info":[{"award-number":["82204657"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research Project of Hainan Province","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}]},{"name":"Key Research Project of Hainan Province","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}]},{"name":"Key Research Project of Hainan Province","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}]},{"name":"Key Research Project of Hainan Province","award":["82204657"],"award-info":[{"award-number":["82204657"]}]},{"name":"Key Research Project of Hainan Province","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}]},{"name":"Key Research Project of Hainan Province","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204657"],"award-info":[{"award-number":["82204657"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["82204657"],"award-info":[{"award-number":["82204657"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}]},{"name":"science and technology planning project of Maoming City","award":["GHYF2024005"],"award-info":[{"award-number":["GHYF2024005"]}]},{"name":"science and technology planning project of Maoming City","award":["2018YFC1706403"],"award-info":[{"award-number":["2018YFC1706403"]}]},{"name":"science and technology planning project of Maoming City","award":["ZDYF2022SHFZ030"],"award-info":[{"award-number":["ZDYF2022SHFZ030"]}]},{"name":"science and technology planning project of Maoming City","award":["82204657"],"award-info":[{"award-number":["82204657"]}]},{"name":"science and technology planning project of Maoming City","award":["2021-I2M-1-032"],"award-info":[{"award-number":["2021-I2M-1-032"]}]},{"name":"science and technology planning project of Maoming City","award":["2022S032"],"award-info":[{"award-number":["2022S032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Depression ranks among the most severe mental health conditions, and poses a burden on global health. Agarwood, an aromatic medicinal plant, has shown potential for improving mental symptoms. As a common folk medicine, agarwood has been applied as an alternative method for mental disorders such as depression through aromatherapy. Previous studies have found that the therapeutic effects of agarwood aromatherapy are primarily related to its volatile components. This study aimed to examine the antidepressant properties and underlying mechanisms of agarwood essential oil (AEO), a collection of the volatile components of agarwood utilized through aromatherapy inhalation and injection administration in mice. Methods: A lipopolysaccharide (LPS)-induced inflammatory depression model was used to evaluate the effects of AEO inhalation and injection on depression-like symptoms. Behavioral assessments included the open-field, tail suspension, and forced swimming tests. Western blot (WB) and ELISA techniques were used to further verify the mechanistic insights. Results: In the LPS-induced depression-like model, AEO inhalation and injection significantly improved depression-like symptoms, decreased immobility duration in both the tail suspension and forced swimming tests in model mice, and reduced the levels of inflammatory cytokines IL-1\u03b2, IL-6, and TNF-\u03b1. WB experiments demonstrated that AEO inhibited the NF-\u03baB\/I\u03baB-\u03b1 inflammatory pathway and activated the BDNF\/TrkB\/CREB pathway in the hippocampus of the LPS-depression model mice. Notably, AEO extracted by hydrodistillation was more effective in alleviating LPS-induced depressive-like behaviors than using supercritical CO2 fluid extraction. Conclusions: Both the inhalation and the injection administration of AEO exerted notable antidepressant effects, potentially associated with reducing inflammation levels in the brain, downregulating inflammatory NF-\u03baB\/I\u03baB-\u03b1, and upregulating the neuroprotective BDNF\/TrkB\/CREB signaling pathway. In the future, it is necessary to further determine the pharmacodynamic components, key targets and specific molecular mechanisms of AEO\u2019s antidepressant effects so as to provide more support for the neuroprotective research of medicinal plants.<\/jats:p>","DOI":"10.3390\/ph18020255","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T04:48:51Z","timestamp":1739508531000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antidepressant Activity of Agarwood Essential Oil: A Mechanistic Study on Inflammatory and Neuroprotective Signaling Pathways"],"prefix":"10.3390","volume":"18","author":[{"given":"Shunan","family":"Zhang","sequence":"first","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-2638","authenticated-orcid":false,"given":"Canhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"School of Biological and Food Engineering, Guangdong University of Petrochemical Technology, Maoming 525011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Gong","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-9300","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"The Burdon Sanderson Cardiac Science Centre and BHF Centre of Research Excellence, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Wu","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-0172","authenticated-orcid":false,"given":"Yangyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhe","family":"Wei","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine & Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education & National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Thompson, R.J., Liu, D.Y., Sudit, E., and Boden, M. (2021). Emotion Differentiation in Current and Remitted Major Depressive Disorder. Front. Psychol., 12.","DOI":"10.3389\/fpsyg.2021.685851"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Vos","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","article-title":"Global Prevalence and Burden of Depressive and Anxiety Disorders in 204 Countries and Territories in 2020 Due to the COVID-19 Pandemic","volume":"398","author":"Santomauro","year":"2021","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.1038\/s41380-024-02625-2","article-title":"Beyond the Serotonin Deficit Hypothesis: Communicating a Neuroplasticity Framework of Major Depressive Disorder","volume":"29","author":"Page","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.brainres.2014.06.032","article-title":"Inflammatory Cytokine-Associated Depression","volume":"1617","author":"Lotrich","year":"2015","journal-title":"Brain Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","article-title":"The Bidirectional Relationship of Depression and Inflammation: Double Trouble","volume":"107","author":"Beurel","year":"2020","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.bbi.2015.06.001","article-title":"Cumulative Meta-Analysis of Interleukins 6 and 1\u03b2, Tumour Necrosis Factor \u03b1 and C-Reactive Protein in Patients with Major Depressive Disorder","volume":"49","author":"Haapakoski","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Majd, M., Saunders, E.F.H., and Engeland, C.G. (2020). Inflammation and the Dimensions of Depression: A Review. Front. Neuroendocr., 56.","DOI":"10.1016\/j.yfrne.2019.100800"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S335","DOI":"10.1192\/j.eurpsy.2021.898","article-title":"Evaluation of Plasma Levels of BDNF in Patients with Disorder Depressive","volume":"64","author":"Galletta","year":"2021","journal-title":"Eur. Psychiat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, T., Nie, Z., Shu, H., Kuang, Y., Chen, X., Cheng, J., Yu, S., and Liu, H. (2020). The Role of BDNF on Neural Plasticity in Depression. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00082"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/ptr.8122","article-title":"Current Understanding and Future Directions of Cruciferous Vegetables and Their Phytochemicals to Combat Neurological Diseases","volume":"38","author":"Kakarla","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_12","unstructured":"Unschuld, P.U., and Zhang, Z. (2014). Dictionary of the Ben Cao Gang Mu. Chinese Historical Illness Terminology, University of California Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.35702\/Trad.10008","article-title":"An Overview of Agarwood, Phytochemical Constituents, Pharmacological Activities, and Analyses","volume":"3","author":"Chen","year":"2022","journal-title":"Tradit. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Alamil, J.M.R., Paudel, K.R., Chan, Y., Xenaki, D., Panneerselvam, J., Singh, S.K., Gulati, M., Jha, N.K., Kumar, D., and Prasher, P. (2022). Rediscovering the Therapeutic Potential of Agarwood in the Management of Chronic Inflammatory Diseases. Molecules, 27.","DOI":"10.3390\/molecules27093038"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Han, M., Zhang, H., Hu, M., Sun, W., Li, Z., Cao, G., Geng, X., and Wei, S. (2021). Inhalation Administration of Agarwood Incense Rescues Scopolamine-Induced Learning and Memory Impairment in Mice. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.821356"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jep.2016.06.055","article-title":"Aquilaria Spp. (Agarwood) as Source of Health Beneficial Compounds: A Review of Traditional Use, Phytochemistry and Pharmacology","volume":"189","author":"Hashim","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tan, C.S., Isa, N.M., Ismail, I., and Zainal, Z. (2019). Agarwood Induction: Current Developments and Future Perspectives. Front. Plant Sci., 10.","DOI":"10.3389\/fpls.2019.00122"},{"key":"ref_18","first-page":"5720","article-title":"Comparative analysis of chemical constituents and anti-oxidant and anti-inflammatory activities of six representative agarwood essential oils","volume":"53","author":"Chen","year":"2022","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chen, X., Wang, C., He, Q., Feng, J., Chen, D., Wei, J., and Liu, Y. (2022). Chemical Composition and Potential Properties in Mental Illness (Anxiety, Depression and Insomnia) of Agarwood Essential Oil: A Review. Molecules, 27.","DOI":"10.3390\/molecules27144528"},{"key":"ref_20","first-page":"4000","article-title":"Composition analysis, antioxidative and antibacterial activities comparison of agarwood oils extracted by supercritical and steam distillation","volume":"44","author":"Tian","year":"2019","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Li, H., Li, Y., Zhang, X., Ren, G., Wang, L., Li, J., Wang, M., Ren, T., Zhao, Y., and Yang, M. (2021). The Combination of Aquilaria Sinensis (Lour.) Gilg and Aucklandia Costus Falc. Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.614413"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, C., Wang, Y., Gong, B., Wu, Y., Chen, X., Liu, Y., and Wei, J. (2022). Effective Components and Molecular Mechanism of Agarwood Essential Oil Inhalation and the Sedative and Hypnotic Effects Based on GC-MS-Qtof and Molecular Docking. Molecules, 27.","DOI":"10.3390\/molecules27113483"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, S., Wang, C., Yu, Z., Wu, C., Peng, D., Liu, X., Liu, Y., Yang, Y., Guo, P., and Wei, J. (2018). Agarwood Essential Oil Ameliorates Restrain Stress-Induced Anxiety and Depression by Inhibiting HPA Axis Hyperactivity. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113468"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, J.-S., Jeon, Y.-J., Kang, J.-Y., Lee, S.-K., Lee, H.-D., and Son, C.-G. (2020). Aquilariae Lignum Methylene Chloride Fraction Attenuates IL-1\u03b2-Driven Neuroinflammation in BV2 Microglial Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155465"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1016\/j.bmc.2006.01.023","article-title":"New Sesquiterpene from Vietnamese Agarwood and Its Induction Effect on Brain-Derived Neurotrophic Factor mRNA Expression in Vitro","volume":"14","author":"Ueda","year":"2006","journal-title":"Bioorg Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"360","DOI":"10.2174\/1573409911309030012","article-title":"Molecular Docking and ADME Studies of Natural Compounds of Agarwood Oil for Topical Anti-Inflammatory Activity","volume":"9","author":"Yadav","year":"2013","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lee, H.-Y., Lee, J.-S., Kim, H.-G., Kim, W.-Y., Lee, S.-B., Choi, Y.-H., and Son, C.-G. (2017). The Ethanol Extract of Aquilariae Lignum Ameliorates Hippocampal Oxidative Stress in a Repeated Restraint Stress Mouse Model. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1902-1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117375","DOI":"10.1016\/j.jep.2023.117375","article-title":"Ononin Ameliorates Depression-like Behaviors by Regulating BDNF-TrkB-CREB Signaling in Vitro and in Vivo","volume":"320","author":"Gong","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhao, X., Kong, D., Zhou, Q., Wei, G., Song, J., Liang, Y., and Du, G. (2021). Baicalein Alleviates Depression-like Behavior in Rotenone- Induced Parkinson\u2019s Disease Model in Mice through Activating the BDNF\/TrkB\/CREB Pathway. Biomed. Pharmacother., 140.","DOI":"10.1016\/j.biopha.2021.111556"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.bbi.2021.10.002","article-title":"Beneficial Effects of QTC-4-MeOBnE in an LPS-Induced Mouse Model of Depression and Cognitive Impairments: The Role of Blood-Brain Barrier Permeability, NF-\u03baB Signaling, and Microglial Activation","volume":"99","author":"Fronza","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_31","first-page":"pyu005","article-title":"Lipopolysaccharide-Induced Depressive-like Behavior Is Associated with A1-Adrenoceptor Dependent Downregulation of the Membrane GluR1 Subunit in the Mouse Medial Prefrontal Cortex and Ventral Tegmental Area","volume":"18","author":"Sekio","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153348","DOI":"10.1016\/j.phymed.2020.153348","article-title":"The Protective Effect of 5-O-Methylvisammioside on LPS-Induced Depression in Mice by Inhibiting the over Activation of BV-2 Microglia through Nf-\u03baB\/I\u03baB-\u03b1 Pathway","volume":"79","author":"Sun","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.bbr.2017.05.064","article-title":"Behavioral, Inflammatory and Neurochemical Disturbances in LPS and UCMS-Induced Mouse Models of Depression","volume":"364","author":"Zhao","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbi.2020.11.008","article-title":"Ibrutinib Alleviates LPS-Induced Neuroinflammation and Synaptic Defects in a Mouse Model of Depression","volume":"92","author":"Li","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.2174\/1381612823666170111141915","article-title":"BDNF\/NF-\u039aB Signaling in the Neurobiology of Depression","volume":"23","author":"Caviedes","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1002\/j.1460-2075.1990.tb07423.x","article-title":"Regional Distribution of Brain-derived Neurotrophic Factor mRNA in the Adult Mouse Brain","volume":"9","author":"Hofer","year":"1990","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.bbrc.2020.07.098","article-title":"Ginsenoside Rk1 Alleviates LPS-Induced Depression-like Behavior in Mice by Promoting BDNF and Suppressing the Neuroinflammatory Response","volume":"530","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","first-page":"1","article-title":"A Simple Role for BDNF in Learning and Memory?","volume":"3","author":"Cunha","year":"2010","journal-title":"Front. Mol. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Miranda, M., Morici, J.F., Zanoni, M.B., and Bekinschtein, P. (2019). Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front. Cell Neurosci., 13.","DOI":"10.3389\/fncel.2019.00363"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s10753-015-0272-4","article-title":"Protective Effect of Astragaloside IV Against Paraquat-Induced Lung Injury in Mice by Suppressing Rho Signaling","volume":"39","author":"Chen","year":"2016","journal-title":"Inflammation"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kaltschmidt, B., Helweg, L.P., Greiner, J.F.W., and Kaltschmidt, C. (2022). NF-\u03baB in Neurodegenerative Diseases: Recent Evidence from Human Genetics. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.954541"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.celrep.2016.05.083","article-title":"I\u03baB Kinase \u03b5 Is an NFATc1 Kinase That Inhibits T Cell Immune Response","volume":"16","author":"Zhang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.pbb.2012.12.003","article-title":"Effects of Antidepressants on Alternations in Serum Cytokines and Depressive-like Behavior in Mice after Lipopolysaccharide Administration","volume":"103","author":"Ohgi","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yu, X., Yao, H., Zhang, X., Liu, L., Liu, S., and Dong, Y. (2022). Comparison of LPS and MS-Induced Depressive Mouse Model: Behavior, Inflammation and Biochemical Changes. BMC Psychiatry, 22.","DOI":"10.1186\/s12888-022-04233-2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jpsychires.2011.08.006","article-title":"Proinflammatory Cytokines in the Prefrontal Cortex of Teenage Suicide Victims","volume":"46","author":"Pandey","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00011-011-0423-5","article-title":"Status of Proinflammatory and Anti-Inflammatory Cytokines in Different Brain Regions of a Rat Model of Japanese Encephalitis","volume":"61","author":"Srivastava","year":"2012","journal-title":"Inflamm. Res."},{"key":"ref_47","first-page":"4436","article-title":"Relationship between Depression and Inflammatory Factors and Brain-Derived Neurotrophic Factor in Patients with Perimenopause Syndrome","volume":"15","author":"Guo","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rossetti, A.C., Paladini, M.S., Trepci, A., Mallien, A., Riva, M.A., Gass, P., and Molteni, R. (2019). Differential Neuroinflammatory Response in Male and Female Mice: A Role for BDNF. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00166"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neulet.2011.07.055","article-title":"Brain-Derived Neurotrophic Factor (BDNF) Infusion Restored Astrocytic Plasticity in the Hippocampus of a Rat Model of Depression","volume":"503","author":"Ye","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbi.2005.04.005","article-title":"Peripheral Immune Activation by Lipopolysaccharide Decreases Neurotrophins in the Cortex and Hippocampus in Rats","volume":"20","author":"Guan","year":"2006","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.bbi.2022.08.005","article-title":"ERK1\/2-Dependent BDNF Synthesis and Signaling Is Required for the Antidepressant Effect of Microglia Stimulation","volume":"106","author":"Lu","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biopsych.2021.05.008","article-title":"Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action","volume":"90","author":"Monteggia","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106099","DOI":"10.1016\/j.phrs.2022.106099","article-title":"Targeting Akt\/CREB\/BDNF Signaling Pathway by Ginsenosides in Neurodegenerative Diseases: A Mechanistic Approach","volume":"177","author":"Zarneshan","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hashemi, P., and Ahmadi, S. (2023). Alpha-Pinene Moderates Memory Impairment Induced by Kainic Acid via Improving the BDNF\/TrkB\/CREB Signaling Pathway in Rat Hippocampus. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1202232"},{"key":"ref_55","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."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/2\/255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:34:12Z","timestamp":1760027652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/2\/255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ph18020255"],"URL":"https:\/\/doi.org\/10.3390\/ph18020255","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]}}}