{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:51:45Z","timestamp":1785527505301,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Agriculture Research System of MOF and MARA","award":["X2022100190618"],"award-info":[{"award-number":["X2022100190618"]}]},{"name":"Undergraduate Research Program (URP) of China Agricultural University, Ministry of Education","award":["X2022100190618"],"award-info":[{"award-number":["X2022100190618"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Depression poses increasing public health challenges, and alternative dietary strategies are gaining attention for their potential therapeutic effects. This study evaluates a natural ingredient-based formula powder (FP) for its antidepressant effects in a chronic unpredictable mild stress (CUMS) mouse model under both a standard diet and high-fat high-sugar diet (HFHSD) conditions. Behavioral tests demonstrated that FP significantly reduced immobility time in the forced swimming test and tail suspension test, and improved anxiety-like behavior in the open field test, particularly by increasing the central zone activity in mice fed a standard diet. FP supplementation also mitigated CUMS- and HFHSD-induced organ damage, as indicated by increased small intestine and colon coefficients. At the molecular level, FP downregulated the expression of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6) and upregulated brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase-2 (TPH2) in the hippocampus and colon. These findings suggest that FP exerts antidepressant-like effects by alleviating neuroinflammation and supporting the gut\u2013brain axis, offering a promising functional food approach for managing depression.<\/jats:p>","DOI":"10.3390\/foods14091640","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T08:20:53Z","timestamp":1746606053000},"page":"1640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preliminary Exploration on the Effects of a Novel Antidepressant Formula Food in a Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Xu","family":"Chen","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"},{"name":"Department of Food Science, University of Massachusetts Amherst, Amherst, MA 01003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxi","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentian","family":"Yue","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5354-1973","authenticated-orcid":false,"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","first-page":"e11","article-title":"Prevalence of mental disorders in China: A cross-sectional epidemiological study","volume":"6","author":"Huang","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_2","first-page":"1023","article-title":"Depression and anxiety symptoms and their comorbidity among Chinese residents in 2021 and 2022","volume":"37","author":"Rong","year":"2023","journal-title":"Chin. J. Ment. Health"},{"key":"ref_3","first-page":"1008","article-title":"Non-suicidal self-injury detection rate and influencing factors in hospitalized children and adolescents with depressive disorders","volume":"50","author":"Yang","year":"2023","journal-title":"Int. J. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jad.2024.01.009","article-title":"Trends in age-standardized incidence rates of depression in adolescents aged 10\u201324 in 204 countries and regions from 1990 to 2019","volume":"350","author":"Hua","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_5","first-page":"255","article-title":"Interpretation of the Chinese Overweight\/Obesity Medical Nutrition Therapy Guidelines (2021)","volume":"13","author":"Sun","year":"2022","journal-title":"Peking. Union. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physiolgenomics.00056.2023","article-title":"Adenylate cyclase 3: A potential genetic link between obesity and major depressive disorder","volume":"56","author":"Fitzpatrick","year":"2024","journal-title":"Physiol. Genom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbi.2022.07.009","article-title":"Overweight, obesity, and individual symptoms of depression: A multicohort study with replication in UK Biobank","volume":"105","author":"Frank","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e4097","DOI":"10.1016\/j.heliyon.2020.e04097","article-title":"Crosstalk between the microbiota-gut-brain axis and depression","volume":"6","author":"Du","year":"2020","journal-title":"Heliyon"},{"key":"ref_9","first-page":"e10280","article-title":"The Gut-Brain Axis and Its Role in Depression","volume":"12","author":"Nanthakumaran","year":"2020","journal-title":"Cureus"},{"key":"ref_10","first-page":"871","article-title":"Review on research progress of depression in traditional Chinese and Western medicine","volume":"45","author":"Tang","year":"2022","journal-title":"J. Beijing Univ. Chin. Med."},{"key":"ref_11","first-page":"498","article-title":"Research progress on mechanisms of polysaccharides in alleviating depression and anxiety symptoms","volume":"37","author":"Su","year":"2023","journal-title":"Chin. J. Pharmacol. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, M., Wang, C., Zhao, K., Ma, S., Sang, J., and Xu, S. (2025). Bioactive compounds from Chinese herbal plants for neurological health: Mechanisms, pathways, and functional food applications. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1537363"},{"key":"ref_13","first-page":"188","article-title":"Research progress on the role of dietary fiber in regulating gut microbiota","volume":"58","author":"Li","year":"2020","journal-title":"Mod. Dr. China"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102621","DOI":"10.1016\/j.ctim.2020.102621","article-title":"Association of dietary fiber and depression symptom: A systematic review and meta-analysis of observational studies","volume":"56","author":"Fatahi","year":"2021","journal-title":"Complement. Ther. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/camh.12387","article-title":"The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents","volume":"25","author":"Esnafoglu","year":"2020","journal-title":"Child. Adolesc. Ment. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2147\/NDT.S399378","article-title":"Vitamin B12, folate, homocysteine, inflammatory mediators (Interleukin-6, TNF-\u03b1, and CRP) levels in adolescents with anxiety or depressive symptoms","volume":"19","author":"Tan","year":"2023","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Somoza-Moncada, M.M., Turrubiates-Hern\u00e1ndez, F.J., Mu\u00f1oz-Valle, J.F., Guti\u00e9rrez-Brito, J.A., D\u00edaz-P\u00e9rez, S.A., Aguayo-Arelis, A., and Hern\u00e1ndez-Bello, J. (2023). Vitamin D in depression: A potential bioactive agent to reduce suicide and suicide attempt risk. Nutrients, 15.","DOI":"10.3390\/nu15071765"},{"key":"ref_18","unstructured":"Bagchi, D. (2014). Nutraceutical and Functional Food Regulations, Elsevier."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1002\/cpz1.208","article-title":"Models of Depression: Unpredictable Chronic Mild Stress in Mice","volume":"1","author":"Nollet","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_20","first-page":"2379","article-title":"Intervention effect of Jiawei Banxia Houpo Decoction on depressed rats","volume":"33","author":"Li","year":"2018","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"149123","DOI":"10.1016\/j.brainres.2024.149123","article-title":"The chronic unpredictable mild stress (CUMS) Paradigm: Bridging the gap in depression research from bench to bedside","volume":"1843","author":"Sharma","year":"2024","journal-title":"Brain Res."},{"key":"ref_22","unstructured":"Wang, Y. (2017). Risk Factors for White Matter Damage and Its Interactive Relationship with Cognition and Depression. [Ph.D. Thesis, Soochow University Dissertation]."},{"key":"ref_23","first-page":"696","article-title":"Study on TNF-\u03b1 and ADP ratio in patients with depression","volume":"53","author":"Feng","year":"2024","journal-title":"Chongqing Med."},{"key":"ref_24","first-page":"77","article-title":"Changes in serum levels of BDNF and TGF-\u03b21 and their relationship with disease severity and cognitive function in patients with depression","volume":"64","author":"Li","year":"2024","journal-title":"Shandong Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41422-022-00645-7","article-title":"Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons","volume":"32","author":"Zhu","year":"2022","journal-title":"Cell Res."},{"key":"ref_26","unstructured":"Tan, T. (2022). Study on the Association Between Abnormal Functional Brain Regions and TPH2 Methylation in Depression. [Master\u2019s Thesis, Southeast University Dissertation]."},{"key":"ref_27","first-page":"346","article-title":"Research progress on the effects of dietary structure and nutrients on depression","volume":"43","author":"Xu","year":"2022","journal-title":"Food Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.appet.2016.09.011","article-title":"Relationship among obesity, depression, and emotional eating in young adults","volume":"107","author":"Lazarevich","year":"2016","journal-title":"Appetite"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.2174\/0118715273291985240430074053","article-title":"Obesity and depression: Common link and possible targets","volume":"23","author":"Jitte","year":"2024","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13237","DOI":"10.1111\/cch.13237","article-title":"Obesity and risk of depressive disorder in children and adolescents: A meta-analysis of observational studies","volume":"50","author":"Chen","year":"2024","journal-title":"Child. Care Health Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.2337\/db18-0469","article-title":"Fpr2 deficiency alleviates diet-induced insulin resistance by reducing weight gain and inhibiting inflammation mediated by macrophage chemotaxis and M1 polarization","volume":"68","author":"Chen","year":"2019","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/nutrit\/nuz072","article-title":"Dietary fiber and its associations with depression and inflammation","volume":"78","author":"Swann","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/10408398.2013.876959","article-title":"Omega 3 polyunsaturated fatty acids and the treatment of depression","volume":"57","author":"Deacon","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_34","first-page":"741","article-title":"Effect of green tea polyphenols on depressive behavior in social defeat mouse models","volume":"50","author":"Liu","year":"2021","journal-title":"Chongqing Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Unno, K., Furushima, D., Tanaka, Y., Tominaga, T., Nakamura, H., Yamada, H., Taguchi, K., Goda, T., and Nakamura, Y. (2022). Improvement of depressed mood with green tea intake. Nutrients, 14.","DOI":"10.3390\/nu14142949"},{"key":"ref_36","first-page":"2018","article-title":"Effects and mechanism of Gastrodia polysaccharides on LPS-induced depressive mice","volume":"24","author":"Liu","year":"2021","journal-title":"China Pharm."},{"key":"ref_37","unstructured":"Yang, X. (2022). Preliminary Study on Prefrontal microRNA-21 Regulating Anxiety-Like Behavior Via the CRF Signaling Pathway. [Master\u2019s Thesis, Zunyi Medical University Dissertation]."},{"key":"ref_38","first-page":"1591","article-title":"Near-infrared light exposure significantly improves intestinal dysfunction caused by depression in rats","volume":"43","author":"Zheng","year":"2023","journal-title":"J. South. Med. Univ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000087097","article-title":"Chronic mild stress (CMS) revisited: Consistency and behavioral-neurobiological concordance in the effects of CMS","volume":"52","author":"Willner","year":"2005","journal-title":"Neuropsychobiology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Albouery, M., Buteau, B., Gregoire, S., Cherbuy, C., Pais, D.-B., Martine, L., Chain, F., Cabaret, S., Berdeaux, O., and Bron, A.M. (2019). Age-related changes in the gut microbiota modify brain lipid composition. Front. Cell Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00444"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12974-024-03104-9","article-title":"Obesity-induced blood-brain barrier dysfunction: Phenotypes and mechanisms","volume":"21","author":"Feng","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref_42","first-page":"6613385","article-title":"Structural brain changes associated with overweight and obesity","volume":"2021","year":"2021","journal-title":"J. Obes."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bbadis.2008.10.004","article-title":"Obesity and vulnerability of the CNS","volume":"1792","author":"Keller","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12979-022-00323-7","article-title":"Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice","volume":"19","author":"Henn","year":"2022","journal-title":"Immun. Ageing"},{"key":"ref_45","first-page":"79","article-title":"Effects of high sugar and high fat diet on intestinal barrier function and inflammation in mice","volume":"23","author":"Shao","year":"2023","journal-title":"J. Chin. Inst. Food Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2100950","DOI":"10.1002\/mnfr.202100950","article-title":"A high-fat high-fructose diet dysregulates the homeostatic crosstalk between gut microbiome, metabolome, and immunity in an experimental model of obesity","volume":"66","author":"Li","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_47","first-page":"100310","article-title":"Diet patterns, gut microbiota and metabolic disorders: Perspectives and challenges","volume":"23","author":"Dalamaga","year":"2024","journal-title":"Elsevier"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yao, H., Yang, J., Li, S., Cui, S., Tan, H., and Nie, S. (2024). Effects of different fractions of polysaccharides from Dictyophora indusiata on high-fat diet-induced metabolic syndrome in mice. Int. J. Biol. Macromol., 272.","DOI":"10.1016\/j.ijbiomac.2024.132744"},{"key":"ref_49","first-page":"1421","article-title":"Bidirectional relationship between ulcerative colitis and depression and anxiety: Based on \u2018disease-induced depression, depression-induced disease\u2019","volume":"33","author":"Zheng","year":"2022","journal-title":"Shizhen Tradit. Chin. Med."},{"key":"ref_50","unstructured":"Liu, Z. (2023). Study on the Effect and Mechanism of 5-ASA and High-Fat Diet in Ulcerative Colitis. [Ph.D. Thesis, Peking Union Medical College Dissertation]."},{"key":"ref_51","first-page":"25","article-title":"Effects of chronic unpredictable stress on dynamic weight changes and inflammatory cytokine levels in mice","volume":"11","author":"Yuan","year":"2021","journal-title":"China Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.ijbiomac.2018.12.146","article-title":"TNF-\u03b1 regulates microglial activation via the NF-\u03baB signaling pathway in systemic lupus erythematosus with depression","volume":"125","author":"Kong","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_53","first-page":"2603","article-title":"Effects of high-fat and high-carbohydrate diets on fat metabolism in rats","volume":"29","author":"Yang","year":"2017","journal-title":"Chin. J. Anim. Nutr."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/9\/1640\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:37Z","timestamp":1760030917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/9\/1640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["foods14091640"],"URL":"https:\/\/doi.org\/10.3390\/foods14091640","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}