{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:07:00Z","timestamp":1788667620490,"version":"build-2803163510"},"reference-count":207,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Creativity and Management Office (RCMO)","award":["USM\/1001\/PPSP\/8012252"],"award-info":[{"award-number":["USM\/1001\/PPSP\/8012252"]}]},{"name":"Universiti Sains Malaysia (USM)","award":["USM\/1001\/PPSP\/8012252"],"award-info":[{"award-number":["USM\/1001\/PPSP\/8012252"]}]},{"name":"School of Medical Sciences, USM","award":["USM\/1001\/PPSP\/8012252"],"award-info":[{"award-number":["USM\/1001\/PPSP\/8012252"]}]},{"name":"Research University Incentive Grant","award":["USM\/1001\/PPSP\/8012252"],"award-info":[{"award-number":["USM\/1001\/PPSP\/8012252"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Depression is a debilitating psychiatric disorder impacting an individual\u2019s quality of life. It is the most prevalent mental illness across all age categories, incurring huge socio-economic impacts. Most depression treatments currently focus on the elevation of neurotransmitters according to the monoamine hypothesis. Conventional treatments include tricyclic antidepressants (TCAs), norepinephrine\u2013dopamine reuptake inhibitors (NDRIs), monoamine oxidase inhibitors (MAOIs), and serotonin reuptake inhibitors (SSRIs). Despite numerous pharmacological strategies utilising conventional drugs, the discovery of alternative medicines from natural products is a must for safer and beneficial brain supplement. About 30% of patients have been reported to show resistance to drug treatments coupled with functional impairment, poor quality of life, and suicidal ideation with a high relapse rate. Hence, there is an urgency for novel discoveries of safer and highly effective depression treatments. Stingless bee honey (SBH) has been proven to contain a high level of antioxidants compared to other types of honey. This is a comprehensive review of the potential use of SBH as a new candidate for antidepressants from the perspective of the monoamine, inflammatory and neurotrophin hypotheses.<\/jats:p>","DOI":"10.3390\/molecules27165091","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T05:43:57Z","timestamp":1660196637000},"page":"5091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pathophysiology of Depression: Stingless Bee Honey Promising as an Antidepressant"],"prefix":"10.3390","volume":"27","author":[{"given":"Fatin Haniza","family":"Zakaria","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Samhani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Medical Campus, Jalan Sultan Mahmud, Kuala Terengganu 20400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-8184","authenticated-orcid":false,"given":"Mohd Zulkifli","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-1852","authenticated-orcid":false,"given":"Nazlahshaniza","family":"Shafin","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00125-006-0159-x","article-title":"Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis","volume":"49","author":"Knol","year":"2006","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/da.20505","article-title":"Nonresponse, partial response, and failure to achieve remission: Humanistic and cost burden in major depressive disorder","volume":"26","author":"Mauskopf","year":"2009","journal-title":"Depress. Anxiety"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3389\/fmed.2017.00196","article-title":"Anxiety and depression in the Portuguese older adults: Prevalence and associated factors","volume":"4","author":"Sousa","year":"2017","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1749-6632.2012.06635.x","article-title":"Antidepressants prevent hierarchy destabilization induced by lipopolysaccharide administration in mice: A neurobiological approach to depression","volume":"1262","author":"Cohn","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1007\/s00213-018-4915-7","article-title":"Novel antidepressant effects of Paeonol alleviate neuronal injury with concomitant alterations in BDNF, Rac1 and RhoA levels in chronic unpredictable mild stress rats","volume":"235","author":"Zhu","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12264-014-1486-4","article-title":"New hypothesis and treatment targets of depression: An integrated view of key findings","volume":"31","author":"Cai","year":"2015","journal-title":"Neurosci. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1192\/bjp.113.504.1237","article-title":"The biochemistry of affective disorders","volume":"113","author":"Coppen","year":"1967","journal-title":"Br. J. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1176\/ajp.122.5.509","article-title":"The catecholamine hypothesis of affective disorders: A review of supporting evidence","volume":"122","author":"Schildkraut","year":"1965","journal-title":"Am. J. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJMra073096","article-title":"Major depressive disorder","volume":"358","author":"Belmaker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.neuroscience.2005.03.051","article-title":"The pathogenesis of clinical depression: Stressor-and cytokine-induced alterations of neuroplasticity","volume":"135","author":"Hayley","year":"2005","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.bbi.2012.06.001","article-title":"A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: Exploring the causes of heterogeneity","volume":"26","author":"Hiles","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/ejn.14630","article-title":"Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants","volume":"53","author":"Duman","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1001\/archpsyc.1997.01830190015002","article-title":"A molecular and cellular theory of depression","volume":"54","author":"Duman","year":"1997","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_14","first-page":"17","article-title":"A Review: Hypothesis of Depression and Role of Antidepressant Drugs","volume":"15","author":"Kharade","year":"2010","journal-title":"Depression"},{"key":"ref_15","first-page":"25","article-title":"How antidepressants help depression: Mechanisms of action and clinical response","volume":"65","author":"Delgado","year":"2004","journal-title":"J. Clin. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cellsig.2004.12.007","article-title":"Mechanisms of action of antidepressants: From neurotransmitter systems to signaling pathways","volume":"17","author":"Taylor","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/10401230209147454","article-title":"Long-term side effects of newer-generation antidepressants: SSRIS, venlafaxine, nefazodone, bupropion, and mirtazapine","volume":"14","author":"Masand","year":"2002","journal-title":"Ann. Clin. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/00048670903107575","article-title":"Sexual side-effects of contemporary antidepressants","volume":"43","author":"Schweitzer","year":"2009","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_19","first-page":"300","article-title":"Do we need new therapeutic strategies for depression?","volume":"23","year":"2011","journal-title":"Psychiatr. Danub."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.euroneuro.2013.05.001","article-title":"Side effects of antidepressants during long-term use in a naturalistic setting","volume":"23","author":"Bet","year":"2013","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1017\/S1461145712001605","article-title":"Multi-modality: A new approach for the treatment of major depressive disorder","volume":"16","author":"Richelson","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"i65","DOI":"10.1136\/bmj.i65","article-title":"Suicidality and aggression during antidepressant treatment: Systematic review and meta-analyses based on clinical study reports","volume":"352","author":"Sharma","year":"2016","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fphar.2011.00006","article-title":"Pharmacogenetics of antidepressants","volume":"2","author":"Crisafulli","year":"2011","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jad.2011.02.020","article-title":"Staging methods for treatment resistant depression. A systematic review","volume":"137","author":"Spijker","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chiu, C.H., Chyau, C.C., Chen, C.C., Lee, L.Y., Chen, W.P., Liu, J.L., Lin, W.H., and Mong, M.C. (2018). Erinacine A-enriched Hericium erinaceus mycelium produces antidepressant-like effects through modulating BDNF\/PI3K\/Akt\/GSK-3\u03b2 signaling in mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020341"},{"key":"ref_26","first-page":"59","article-title":"Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog. Neuro-Psychopharmacol","volume":"59","author":"Manosso","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/10520295.2017.1323276","article-title":"The antidepressant-like effect of Ocimum basilicum in an animal model of depression","volume":"92","author":"Ali","year":"2017","journal-title":"Biotech. Histochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.3390\/molecules17044400","article-title":"Honey: A novel antioxidant","volume":"17","author":"Erejuwa","year":"2012","journal-title":"Molecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"958721","DOI":"10.1155\/2014\/958721","article-title":"Neurological effects of honey: Current and future prospects","volume":"2014","author":"Gan","year":"2014","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"869","DOI":"10.3892\/mco.2015.559","article-title":"Bee pollen and honey for the alleviation of hot flushes and other menopausal symptoms in breast cancer patients","volume":"3","author":"Voss","year":"2015","journal-title":"Mol. Clin. Oncol."},{"key":"ref_31","first-page":"144","article-title":"Exploring the use of and perceptions about honey as complementary and alternative medicine among the general public in the state of Selangor, Malaysia","volume":"7","author":"Othman","year":"2017","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_32","first-page":"187","article-title":"Physicochemical characteristics of Malaysian stingless bee honey from trigona species","volume":"17","author":"Fatima","year":"2018","journal-title":"IIUM Med. J. Malays."},{"key":"ref_33","first-page":"145","article-title":"Asid fenolik bebas dalam madu kelulut","volume":"2","author":"Roowi","year":"2012","journal-title":"Bul. Teknol. MARDI"},{"key":"ref_34","first-page":"648","article-title":"Ethnomedicinal uses of honey of stingless bee by Nepali community of Darjeeling foothills of West Bengal, India","volume":"16","author":"Biswa","year":"2017","journal-title":"Indian J. Tradit. Knowl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.foodchem.2012.09.064","article-title":"Rapid analysis of sugars in honey by processing Raman spectrum using chemometric methods and artificial neural networks","volume":"136","author":"Boyaci","year":"2013","journal-title":"Food Chem."},{"key":"ref_36","first-page":"150","article-title":"Total phenolic contents and colour intensity of Malaysian honeys from the Apis spp. and Trigona spp. bees. Agric","volume":"2","author":"Kek","year":"2014","journal-title":"Agric. Sci. Procedia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.foodchem.2014.03.016","article-title":"5-HMF and carbohydrates content in stingless bee honey by CE before and after thermal treatment","volume":"159","author":"Biluca","year":"2014","journal-title":"Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.biopha.2017.01.066","article-title":"Rutin attenuates H2O2-induced oxidation damage and apoptosis in Leydig cells by activating PI3K\/Akt signal pathways","volume":"88","author":"Sun","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12291-016-0603-8","article-title":"Influence of the flavonoid, quercetin on antioxidant status, lipid peroxidation and histopathological changes in hyperammonemic rats","volume":"32","author":"Kanimozhi","year":"2017","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_40","first-page":"4","article-title":"Relationship of neurotransmitters to the symptoms of major depressive disorder","volume":"69","author":"Nutt","year":"2008","journal-title":"J. Clin. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13020-019-0246-9","article-title":"Botanicals as modulators of depression and mechanisms involved","volume":"14","author":"Zhang","year":"2019","journal-title":"Chin. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e202103052","DOI":"10.1083\/jcb.202103052","article-title":"The cell biology of synapse formation","volume":"220","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.2174\/0929867043364784","article-title":"Structure and mechanism of monoamine oxidase","volume":"11","author":"Edmondson","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1100\/tsw.2009.137","article-title":"Potentials of curcumin as an antidepressant","volume":"9","author":"Kulkarni","year":"2009","journal-title":"Sci. World J."},{"key":"ref_45","first-page":"9","article-title":"The importance of norepinephrine in depression. Neuropsychiatr","volume":"7","author":"Moret","year":"2011","journal-title":"Dis. Treat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1056\/NEJM195412162512504","article-title":"Mental depression in hypertensive patients treated for long periods with large doses of reserpine","volume":"251","author":"Freis","year":"1954","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/BF02041242","article-title":"The discovery of antidepressants: A winding path","volume":"47","author":"Pletscher","year":"1991","journal-title":"Experientia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jshs.2013.04.001","article-title":"The complex role of physical exercise and reactive oxygen species on brain","volume":"2","author":"Radak","year":"2013","journal-title":"J. Sport Health Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"189","DOI":"10.5607\/en.2018.27.3.189","article-title":"Antidepressant-like effects of p-coumaric acid on LPS-induced depressive and inflammatory changes in rats","volume":"27","author":"Lee","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1023\/A:1023287729363","article-title":"Central GABAergic systems and depressive illness","volume":"28","author":"Tunnicliff","year":"2003","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/15622970600868525","article-title":"GABAA receptors as targets for novel anxiolytic drugs","volume":"7","author":"Rupprecht","year":"2006","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1089\/omi.2006.10.444","article-title":"Genome wide gene expression studies in mood disorders","volume":"10","author":"Sequeira","year":"2006","journal-title":"Omics A J. Integr. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2174\/187152707780363294","article-title":"GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol","volume":"6","author":"Sanacora","year":"2007","journal-title":"Disord.-Drug Targets (Former. Curr. Drug Targets-CNS Neurol. Disord.)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/glia.21087","article-title":"Astrocytes are GABAergic cells that modulate microglial activity","volume":"59","author":"Lee","year":"2011","journal-title":"Glia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF-\u03baB family of transcription factors and its regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1017\/S1461145702003103","article-title":"The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans","volume":"5","author":"Wichers","year":"2002","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri1703","article-title":"NF-\u03baB: Linking inflammation and immunity to cancer development and progression","volume":"5","author":"Karin","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-biophys-083012-130338","article-title":"Molecular basis of NF-\u03baB signaling","volume":"42","author":"Napetschnig","year":"2013","journal-title":"Annu. Rev. Biophys."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nm.3586","article-title":"Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-\u03baB","volume":"20","author":"Yu","year":"2014","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/nrd1225","article-title":"COX-2 and beyond: Approaches to prostaglandin inhibition in human disease","volume":"2","author":"FitzGerald","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1523\/JNEUROSCI.4398-05.2006","article-title":"Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-\u03baB in the frontal cortex and hippocampus via glucocorticoid secretion","volume":"26","author":"Munhoz","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","article-title":"Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression","volume":"65","author":"Miller","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s12264-013-1439-3","article-title":"Inflammation: A mechanism of depression?","volume":"30","author":"Han","year":"2014","journal-title":"Neurosci. Bull."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e463","DOI":"10.1038\/tp.2014.92","article-title":"Peripherally triggered and GSK-3\u03b2-driven brain inflammation differentially skew adult hippocampal neurogenesis, behavioral pattern separation and microglial activation in response to ibuprofen","volume":"4","author":"Hernandez","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.lfs.2015.10.020","article-title":"Ibuprofen ameliorates fatigue-and depressive-like behavior in tumor-bearing mice","volume":"143","author":"Norden","year":"2015","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1073\/pnas.0708092105","article-title":"IL-1\u03b2 is an essential mediator of the antineurogenic and anhedonic effects of stress","volume":"105","author":"Koo","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: When the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_68","first-page":"4074051","article-title":"Inflammatory profiles in depressed adolescents treated with fluoxetine: An 8-week follow-up open study","volume":"2018","author":"Arreola","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_69","first-page":"34","article-title":"Anti-inflammatory cytokine levels in patients with septic shock. Res. Commun","volume":"98","author":"Kasai","year":"1997","journal-title":"Mol. Pathol. Pharmacol."},{"key":"ref_70","first-page":"756357","article-title":"A Review: Inflammatory Process in Alzheimer\u2019s Disease, Role of Cytokines","volume":"2012","year":"2012","journal-title":"Sci. World J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A Meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/mp.2017.205","article-title":"Chemokines in depression in health and in inflammatory illness: A systematic review and meta-analysis","volume":"23","author":"Leighton","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1126\/science.1222939","article-title":"Synaptic dysfunction in depression: Potential therapeutic targets","volume":"338","author":"Duman","year":"2012","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.pharmthera.2011.01.014","article-title":"Immune system to brain signaling: Neuropsychopharmacological implications","volume":"130","author":"Capuron","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/npp.2016.199","article-title":"Inflammation, glutamate, and glia: A trio of trouble in mood disorders","volume":"42","author":"Haroon","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-2094-8-12","article-title":"Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice","volume":"8","author":"Park","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3233\/JAD-2011-111097","article-title":"The role of indoleamine 2, 3-dioxygenase in a mouse model of neuroinflammation-induced depression","volume":"28","author":"Dobos","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1186\/1742-2094-10-87","article-title":"Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2, 3-dioxygenase-dependent depression-like behaviors","volume":"10","author":"Lawson","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3389\/fnins.2018.00499","article-title":"Brain kynurenine and BH4 pathways: Relevance to the pathophysiology and treatment of inflammation-driven depressive symptoms","volume":"12","author":"Vancassel","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3389\/fpsyg.2017.01561","article-title":"The relationships among tryptophan, kynurenine, indoleamine 2, 3-dioxygenase, depression, and neuropsychological performance","volume":"8","author":"Hestad","year":"2017","journal-title":"Front. Psychol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.mp.4002148","article-title":"Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2, 3-dioxygenase activation in mice","volume":"14","author":"Lawson","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/mp.2009.116","article-title":"CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-\u03b1: Relationship to CNS immune responses and depression","volume":"15","author":"Raison","year":"2010","journal-title":"Mol. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neuropharm.2016.08.003","article-title":"The kynurenine pathway and the brain: Challenges, controversies and promises","volume":"112","author":"Schwarcz","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8258307","DOI":"10.1155\/2019\/8258307","article-title":"Stingless bee honey improves spatial memory in mice, probably associated with brain-derived neurotrophic factor (BDNF) and inositol 1, 4, 5-triphosphate receptor type 1 (Itpr1) genes","volume":"2019","author":"Mustafa","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s10545-017-0115-6","article-title":"AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria","volume":"41","author":"Lu","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_86","first-page":"95","article-title":"Mechanisms of inflammation-associated depression: Immune influences on tryptophan and phenylalanine metabolisms","volume":"31","author":"Strasser","year":"2016","journal-title":"Inflamm.-Assoc. Depress. Evid. Mech. Implic."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cobeha.2018.01.027","article-title":"Chemical neuromodulation of cognitive control avoidance","volume":"22","author":"Cools","year":"2018","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/npp.2011.205","article-title":"Psychoneuroimmunology meets neuropsychopharmacology: Translational implications of the impact of inflammation on behavior","volume":"37","author":"Haroon","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"622","DOI":"10.2174\/138920008785821738","article-title":"Chronic immune stimulation correlates with reduced phenylalanine turnover","volume":"9","author":"Neurauter","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1098\/rstb.2011.0357","article-title":"A neurotrophic hypothesis of depression: Role of synaptogenesis in the actions of NMDA receptor antagonists","volume":"367","author":"Duman","year":"2012","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1042\/CS20160009","article-title":"Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions","volume":"131","author":"Begni","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_92","first-page":"e5106","article-title":"Brain-Derived Neurotrophic Factor\u2014Major Depressive Disorder and Suicide","volume":"6","author":"Galea","year":"2019","journal-title":"Open Access Libr. J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuropharm.2015.10.034","article-title":"BDNF\u2013a key transducer of antidepressant effects","volume":"102","author":"Monteggia","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"231","DOI":"10.4306\/pi.2010.7.4.231","article-title":"The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment","volume":"7","author":"Lee","year":"2010","journal-title":"Psychiatry Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrn3379","article-title":"Neurotrophin regulation of neural circuit development and function","volume":"14","author":"Park","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-3-642-45106-5_9","article-title":"BDNF and synaptic plasticity, cognitive function, and dysfunction","volume":"220","author":"Lu","year":"2014","journal-title":"Neurotrophic Factors"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12993-016-0101-4","article-title":"BDNF DNA methylation changes as a biomarker of psychiatric disorders: Literature review and open access database analysis","volume":"12","author":"Zheleznyakova","year":"2016","journal-title":"Behav. Brain Funct."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0165-6147(99)01309-7","article-title":"Neurotrophins and depression","volume":"20","author":"Altar","year":"1999","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Numakawa, T., Odaka, H., and Adachi, N. (2018). Actions of brain-derived neurotrophin factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113650"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1111\/bph.13061","article-title":"MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway","volume":"172","author":"Zhu","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/s41401-019-0238-4","article-title":"Curculigoside facilitates fear extinction and prevents depression-like behaviors in a mouse learned helplessness model through increasing hippocampal BDNF","volume":"40","author":"Yang","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00213-014-3690-3","article-title":"7-Chlorokynurenic acid (7-CTKA) produces rapid antidepressant-like effects: Through regulating hippocampal microRNA expressions involved in TrkB-ERK\/Akt signaling pathways in mice exposed to chronic unpredictable mild stress","volume":"232","author":"Liu","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6903","DOI":"10.1038\/s41598-017-07407-1","article-title":"Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism","volume":"7","author":"Yan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zhang, X., Song, Y., Bao, T., Yu, M., Xu, M., Guo, Y., Wang, Y., Zhang, C., and Zhao, B. (2016). Antidepressant-like effects of acupuncture involved the ERK signaling pathway in rats. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1356-x"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biopha.2018.04.035","article-title":"The antidepressant-like effects of Chaihu Shugan San: Dependent on the hippocampal BDNF-TrkB-ERK\/Akt signaling activation in perimenopausal depression-like rats","volume":"105","author":"Chen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0896-6273(03)00228-9","article-title":"Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons","volume":"38","author":"Man","year":"2003","journal-title":"Neuron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/1073858410365562","article-title":"Ras and Rap signaling in synaptic plasticity and mental disorders","volume":"17","author":"Stornetta","year":"2011","journal-title":"Neuroscientist"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopsych.2006.02.013","article-title":"A neurotrophic model for stress-related mood disorders","volume":"59","author":"Duman","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.tins.2011.11.004","article-title":"Signaling pathways underlying the pathophysiology and treatment of depression: Novel mechanisms for rapid-acting agents","volume":"35","author":"Duman","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3389\/fgene.2013.00297","article-title":"G protein-linked signaling pathways in bipolar and major depressive disorders","volume":"4","author":"Tomita","year":"2013","journal-title":"Front. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/nn.4066","article-title":"The role of ventral striatal cAMP signaling in stress-induced behaviors","volume":"18","author":"Plattner","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nm.4050","article-title":"Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants","volume":"22","author":"Duman","year":"2016","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/brain\/awr039","article-title":"Harnessing neuroplasticity for clinical applications","volume":"134","author":"Cramer","year":"2011","journal-title":"Brain"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00213-018-4950-4","article-title":"Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression","volume":"235","author":"Levy","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fnins.2016.00026","article-title":"Regulation of neurogenesis by neurotrophins during adulthood: Expected and unexpected roles","volume":"10","author":"Vilar","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000368575","article-title":"Neurogenesis in the normal ageing hippocampus: A mini-review","volume":"61","author":"Seib","year":"2015","journal-title":"Gerontology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1126\/science.1222941","article-title":"Depression and hippocampal neurogenesis: A road to remission?","volume":"338","author":"Eisch","year":"2012","journal-title":"Science"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1176\/ajp.157.1.115","article-title":"Hippocampal volume reduction in major depression","volume":"157","author":"Bremner","year":"2000","journal-title":"Am. J. Psychiatry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jad.2011.05.057","article-title":"Hippocampal atrophy in first episode depression: A meta-analysis of magnetic resonance imaging studies","volume":"134","author":"Cole","year":"2011","journal-title":"J. Affect. Disord."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1001\/archpsyc.64.4.410","article-title":"Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression","volume":"64","author":"Frodl","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nature07455","article-title":"The molecular neurobiology of depression","volume":"455","author":"Krishnan","year":"2008","journal-title":"Nature"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/dneu.20758","article-title":"The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity","volume":"70","year":"2010","journal-title":"Dev. Neurobiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0079-6123(00)26027-5","article-title":"Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression","volume":"126","author":"Drevets","year":"2000","journal-title":"Prog. Brain Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/neu.20025","article-title":"Chronic stress alters dendritic morphology in rat medial prefrontal cortex","volume":"60","author":"Cook","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"455","DOI":"10.31887\/DCNS.2013.15.4\/cpittenger","article-title":"Disorders of memory and plasticity in psychiatric disease","volume":"15","author":"Pittenger","year":"2013","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.drudis.2016.01.016","article-title":"Emerging treatment mechanisms for depression: Focus on glutamate and synaptic plasticity","volume":"21","author":"Gerhard","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.tins.2012.12.010","article-title":"Neuronal plasticity and antidepressant actions","volume":"36","author":"Hen","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/381706a0","article-title":"Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus","volume":"381","author":"Figurov","year":"1996","journal-title":"Nature"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1126\/science.1067766","article-title":"Postsynaptic induction of BDNF-mediated long-term potentiation","volume":"295","author":"Kovalchuk","year":"2002","journal-title":"Science"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1126\/science.1152864","article-title":"Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines","volume":"319","author":"Tanaka","year":"2008","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1001\/archgenpsychiatry.2011.60","article-title":"Structural neuroimaging studies in major depressive disorder: Meta-analysis and comparison with bipolar disorder","volume":"68","author":"Kempton","year":"2011","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.conb.2014.08.012","article-title":"The current state of the neurogenic theory of depression and anxiety","volume":"30","author":"Miller","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.euroneuro.2011.05.003","article-title":"Magnetic resonance imaging studies in unipolar depression: Systematic review and meta-regression analyses","volume":"22","author":"Arnone","year":"2012","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1176\/appi.ajp.161.11.1957","article-title":"Hippocampal volume and depression: A meta-analysis of MRI studies","volume":"161","author":"Videbech","year":"2004","journal-title":"Am. J. Psychiatry"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/sj.npp.1301574","article-title":"Stress, depression, and neuroplasticity: A convergence of mechanisms","volume":"33","author":"Pittenger","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrn849","article-title":"The stressed hippocampus, synaptic plasticity and lost memories","volume":"3","author":"Kim","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.neuroscience.2009.08.053","article-title":"Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery","volume":"164","author":"Goldwater","year":"2009","journal-title":"Neuroscience"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/387497a0","article-title":"Behavioural stress facilitates the induction of long-term depression in the hippocampus","volume":"387","author":"Xu","year":"1997","journal-title":"Nature"},{"key":"ref_139","first-page":"142","article-title":"\u2018Miel de Angelita\u2019: Nutritional composition and physicochemical properties of Tetragonisca angustula honey","volume":"37","author":"Fuenmayor","year":"2012","journal-title":"Interciencia"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.lwt.2013.09.024","article-title":"Physicochemical characteristics of minor monofloral honeys from Tenerife, Spain","volume":"55","author":"Manzanares","year":"2014","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_141","first-page":"70","article-title":"A review on beekeeping in Malaysia: History, importance and future directions","volume":"11","author":"Ismail","year":"2016","journal-title":"J. Sustain. Sci. Manag."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"888","DOI":"10.3923\/pjn.2017.888.894","article-title":"Physicochemical and antioxidant potential of raw unprocessed honey from Malaysian stingless bees","volume":"16","author":"Bakar","year":"2017","journal-title":"Pak. J. Nutr."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21315\/mjms2018.25.4.1","article-title":"Reinventing the honey industry: Opportunities of the stingless bee","volume":"25","author":"Mustafa","year":"2018","journal-title":"Malays. J. Med. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Litwack, G. (2018). Chapter 13\u2014Metabolism of Amino Acids. Human Biochemistry, Academic Press.","DOI":"10.1016\/B978-0-12-383864-3.00013-2"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.4103\/1673-5374.235219","article-title":"Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: Implications for Parkinson\u2019s disease","volume":"13","author":"Harkin","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.neubiorev.2013.11.009","article-title":"Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects","volume":"38","author":"Mahar","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev.clinpsy.121208.131305","article-title":"Cognition and depression: Current status and future directions","volume":"6","author":"Gotlib","year":"2010","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/ijnp\/pyx056","article-title":"Dopamine system dysregulation in major depressive disorders","volume":"20","author":"Belujon","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.neulet.2016.08.044","article-title":"Caffeic acid attenuates lipopolysaccharide-induced sickness behaviour and neuroinflammation in mice","volume":"632","author":"Mallik","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12986-019-0341-z","article-title":"Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-\u03baB and p38 MAPK","volume":"16","author":"Ranneh","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3896\/IBRA.4.03.4.01","article-title":"Role of honey polyphenols in health","volume":"3","author":"Uthurry","year":"2011","journal-title":"J. ApiProduct ApiMedical Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"C921","DOI":"10.1111\/j.1750-3841.2011.02282.x","article-title":"Phenolic acid composition and antioxidant properties of Malaysian honeys","volume":"76","author":"Khalil","year":"2011","journal-title":"J. Food Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.aca.2004.11.010","article-title":"Standardization of antioxidant properties of honey by a combination of spectrophotometric\/fluorimetric assays and chemometrics","volume":"533","author":"Beretta","year":"2005","journal-title":"Anal. Chim. Acta"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.foodchem.2007.01.060","article-title":"Evaluation of the phenolic content, antioxidant activity and colour of Slovenian honey","volume":"105","author":"Bertoncelj","year":"2007","journal-title":"Food Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.foodchem.2004.10.006","article-title":"Determination of the total phenolic, flavonoid and proline contents in Burkina Fasan honey, as well as their radical scavenging activity","volume":"91","author":"Meda","year":"2005","journal-title":"Food Chem."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Moniruzzaman, M., Khalil, M.I., Sulaiman, S.A., and Gan, S.H. (2013). Physicochemical and antioxidant properties of Malaysian honeys produced by Apis cerana, Apis dorsata and Apis mellifera. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-43"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0197-4580(02)00078-7","article-title":"A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes","volume":"23","author":"Esposito","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.neurobiolaging.2005.08.007","article-title":"The beneficial effects of fruit polyphenols on brain aging","volume":"26","author":"Lau","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_159","first-page":"23","article-title":"Flavonoids and the aging brain","volume":"56","author":"Schaffer","year":"2005","journal-title":"J. Physiol. Pharmacol. Suppl."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1549158","DOI":"10.1155\/2016\/1549158","article-title":"Tualang honey attenuates noise stress-induced memory deficits in aged rats","volume":"2016","author":"Azman","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.pnpbp.2010.08.026","article-title":"In animal models, psychosocial stress-induced (neuro) inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression","volume":"35","author":"Kubera","year":"2011","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.psyneuen.2016.11.031","article-title":"Oxidative stress, inflammation and treatment response in major depression","volume":"76","author":"Lindqvist","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.pnpbp.2017.06.036","article-title":"The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression","volume":"80","author":"Czarny","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"5762172","DOI":"10.1155\/2017\/5762172","article-title":"Antidepressant flavonoids and their relationship with oxidative stress","volume":"2017","author":"Hritcu","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S1043-6618(03)00214-7","article-title":"Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat\u2019s heart","volume":"48","author":"Helal","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/mnfr.200500014","article-title":"Antioxidant and antigenotoxic effects of plant cell wall hydroxycinnamic acids in cultured HT-29 cells","volume":"49","author":"Ferguson","year":"2005","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.abb.2010.03.016","article-title":"Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity","volume":"501","author":"Vauzour","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ejphar.2016.09.005","article-title":"Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice","volume":"791","author":"Filho","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.cbi.2016.11.005","article-title":"Chrysin promotes attenuation of depressive-like behavior and hippocampal dysfunction resulting from olfactory bulbectomy in mice","volume":"260","author":"Filho","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1021\/jf501314g","article-title":"p-Coumaric acid and ursolic acid from corni fructus attenuated \u03b2-Amyloid25\u201335-induced toxicity through regulation of the NF-\u03baB signaling pathway in PC12 cells","volume":"62","author":"Yoon","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s11011-017-0039-8","article-title":"Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats","volume":"32","author":"Yousef","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_172","first-page":"1560","article-title":"Effect of p-coumaric acid against oxidative stress induced by cisplatin in brain tissue of rats","volume":"27","author":"Alwasel","year":"2017","journal-title":"J. Anim. Plant Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11011-018-0185-7","article-title":"Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries","volume":"33","author":"Sakamula","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1472-8206.2012.01040.x","article-title":"Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress","volume":"27","author":"Chhillar","year":"2013","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_175","first-page":"575","article-title":"Evaluation of antidepressant activity of gallic acid in mice","volume":"5","author":"Pemminati","year":"2014","journal-title":"Res. J. Pharm. Biol. Chem. Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.lfs.2017.09.023","article-title":"Antidepressant-like effect of gallic acid in mice: Dual involvement of serotonergic and catecholaminergic systems","volume":"190","author":"Can","year":"2017","journal-title":"Life Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejphar.2018.01.017","article-title":"Chrysin reverses the depressive-like behavior induced by hypothyroidism in female mice by regulating hippocampal serotonin and dopamine","volume":"822","author":"Bortolotto","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_178","first-page":"1","article-title":"Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression","volume":"5","author":"Ehrhart","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_179","first-page":"322","article-title":"Evaluation of antidepressant-like effects of aqueous and ethanolic extracts of Pimpinella anisum fruit in mice","volume":"6","author":"Shahamat","year":"2016","journal-title":"Avicenna J. Phytomed."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbr.2015.09.031","article-title":"Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1\u03b2 production and NLRP3 inflammasome activation in the rat brain","volume":"296","author":"Li","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_181","first-page":"2867","article-title":"The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR\/AMPK\/ULK1 pathway","volume":"20","author":"Zhang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"31450","DOI":"10.1038\/srep31450","article-title":"Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer\u2019s disease","volume":"6","author":"Balez","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jff.2018.07.037","article-title":"Apigenin: A natural bioactive flavone-type molecule with promising therapeutic function","volume":"48","author":"Kashyap","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1248\/bpb.26.474","article-title":"Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test","volume":"26","author":"Nakazawa","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.lfs.2008.01.007","article-title":"Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin","volume":"82","author":"Yi","year":"2008","journal-title":"Life Sci."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neulet.2015.03.040","article-title":"The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice","volume":"594","author":"Li","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejphar.2016.01.015","article-title":"Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice","volume":"774","author":"Weng","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cbi.2017.03.016","article-title":"Protective role of apigenin on rotenone induced rat model of Parkinson\u2019s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis","volume":"269","author":"Anusha","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1073\/pnas.0913572107","article-title":"A selective TrkB agonist with potent neurotrophic activities by 7, 8-dihydroxyflavone","volume":"107","author":"Jang","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jfda.2016.03.003","article-title":"Influence of gallic acid on \u03b1-amylase and \u03b1-glucosidase inhibitory properties of acarbose","volume":"24","author":"Oboh","year":"2016","journal-title":"J. Food Drug Anal."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4103\/1673-5374.198964","article-title":"Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury","volume":"12","author":"Wurzelmann","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_192","first-page":"28","article-title":"Effect of quercetin on the brain-derived neurotrophic factor gene expression in the rat brain","volume":"119","author":"Rahvar","year":"2018","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.2174\/1381612823666170111141915","article-title":"BDNF\/NF-\u03baB Signaling in the Neurobiology of Depression","volume":"23","author":"Caviedes","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10571-017-0510-4","article-title":"BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity","volume":"38","author":"Lietzau","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1089\/jmf.2013.0024","article-title":"Topical anti-inflammatory activity of a monofloral honey of Mimosa scabrella provided by Melipona marginata during winter in Southern Brazil","volume":"17","author":"Borsato","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.neuropharm.2011.08.018","article-title":"Depressive-like behavior induced by tumor necrosis factor-\u03b1 in mice","volume":"62","author":"Kaster","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s11064-005-2678-0","article-title":"In vivo quinolinic acid increases synaptosomal glutamate release in rats: Reversal by guanosine","volume":"30","author":"Tavares","year":"2005","journal-title":"Neurochem. Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1017\/S1092852900016734","article-title":"Inflammation, glutamate, and glia in depression: A literature review","volume":"13","author":"McNally","year":"2008","journal-title":"CNS Spectr."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.psyneuen.2010.09.012","article-title":"Inflammation-associated depression: From serotonin to kynurenine","volume":"36","author":"Dantzer","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jsbmb.2007.09.014","article-title":"Neuronal actions of glucocorticoids: Focus on depression","volume":"108","author":"Yu","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"790","DOI":"10.3389\/fpsyt.2021.655453","article-title":"Relaxation Response in Stressed Volunteers: Psychometric Tests and Neurotrophin Changes in Biological Fluids","volume":"12","author":"Zappella","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1113\/EP088605","article-title":"Combination of quercetin and exercise training attenuates depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer: Possible involvement of inflammation and BDNF signalling","volume":"105","author":"Sadighparvar","year":"2020","journal-title":"Exp. Physiol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2174\/1570159X14666160119094646","article-title":"Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets","volume":"14","author":"Zhang","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_204","first-page":"17","article-title":"Inflammation and treatment resistance in major depression: A perfect storm","volume":"30","author":"Raison","year":"2013","journal-title":"Psychiatr. Times"},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Strawbridge, R., Young, A.H., and Cleare, A.J. (2018). Inflammation as a marker of clinical response to treatment: A focus on treatment-resistant depression. Inflammation and Immunity in Depression, Academic Press.","DOI":"10.1016\/B978-0-12-811073-7.00027-1"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jad.2018.12.037","article-title":"Inflammatory profiles of severe treatment-resistant depression","volume":"246","author":"Strawbridge","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1177\/0269881117725711","article-title":"Anti-inflammatory treatments for mood disorders: Systematic review and meta-analysis","volume":"31","author":"Husain","year":"2017","journal-title":"J. Psychopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/16\/5091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:58Z","timestamp":1760141218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/16\/5091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":207,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["molecules27165091"],"URL":"https:\/\/doi.org\/10.3390\/molecules27165091","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,10]]}}}