Abstract
［Objective］ This study aims to investigate the anti -depression effects of enzymatic hydrolysates of mulberry leaf flavonoids (EMLF ).［Methods］ EMLF was prepared and its components were analyzed by UPLC -MS.A zebrafish model of depression was induced by 40 mg/L reserpine.Six groups were designed,including the control,model,fluoxetine,L-EMLF (20 μg/mL ),M-EMLF (40 μg/mL ),and H-EMLF (80 μg/mL ) groups.Behavioral tests,including the new tank test and the light -dark box test,were conducted.The structural changes in the brain tissue of zebrafish in each group were observed by HE staining.The mRNA levels of interleukin -1β (IL-1β),tumor necrosis factor -α (TNF-α),tryptophan hydroxylase -2 (TPH- 2),and 5-hydroxytryptamine 2A (5-HT2A) receptor in the brain tissue were determined by q -PCR.The activity of superoxide dismutase (SOD ) and the level of reactive oxygen species (ROS ) in the brain tissue of zebrafish were measured.Metabolomics analysis was performed to identify differential metabolites and associated metabolic pathways.贾东升（1982—），男，河北省农林科学院副研究员，博士。E-mail：jiads 1@163.com|［Results］］ UPLC -MS identified 10 flavonoid aglycone compounds.Reserpine (40 mg/L ) induced depression -like behaviors in zebrafish,while EMLF alleviated the bottom -dwelling and dark -preference behaviors,restored the orderly arrangement of nerve cells in the midbrain region,and increased the cell number.EMLF treatment down -regulated the mRNA levels of IL-1β,TNF-α,and 5-HT2A while up -regulating the mRNA level of TPH- 2.In addition,EMLF increased the SOD activity and reduced the ROS level.Metabolomics analysis revealed that EMLF significantly regulated 24 differential metabolites,primarily affecting purine metabolism,arginine and proline metabolism,tryptophan metabolism,and riboflavin metabolism.［Conclusion］ EMLF effectively alleviated reserpine -induced depression in zebrafish,potentially by regulating the tryptophan metabolism,purine metabolism,and arginine and proline metabolism.
Publication Date
2-18-2025
First Page
118
Last Page
128
DOI
10.13652/j.spjx.1003.5788.2024.80655
Recommended Citation
Xuan, ZHENG; Yunke, LU; Chunling, ZHOU; Ju, ZHANG; Mingxue, WANG; Shizhan, CUI; and Dongsheng, JIA
(2025)
"Enzymatic hydrolysates of mulberry leaf flavonoids alleviate depression induced by reserpine in zebrafish,"
Food and Machinery: Vol. 40:
Iss.
12, Article 16.
DOI: 10.13652/j.spjx.1003.5788.2024.80655
Available at:
https://www.ifoodmm.cn/journal/vol40/iss12/16
References
[1] 郑涵文,王梓航,刘昕玥,等.黄花菜醇提物对斑马鱼抑郁样行为的改善作用研究 [J].中国比较医学杂志,2024,34(4):20-27.ZHENG H W,WANG Z H,LIU X Y,et al.Improvement of depressive-like behavior in Hemerocallis citrina Baroni using a zebrafish model [J].Chinese Journal of Comparative Medicine,2024,34(4):20-27.
[2] MEDEIROS G C,ROY D,KONTOS N,et al.Post-stroke depression:a 2020 updated review [J].General Hospital Psychiatry,2020,66:70-80.
[3] CALDIROLI A,CAPUZZI E,TAGLIABUE I,et al.Augmentative pharmacological strategies in treatment-resistant major depression:a comprehensive review [J].International Journal of Molecular Sciences,2021,22(23):13070.
[4] 李晓辉,杜冠华.新药研究与评价概论 [M].2版.北京:人民卫生出版社,2022:342.LI X H,DU G H.Introduction to new drug research and evaluation [M].2nd ed.Beijing:People's Medical Publishing House,2022:342.
[5] 黄越,黄传书,吴均,等.桑资源生物活性物质及其在食品领域应用研究进展 [J].食品与发酵工业,2023,49(23):362-370.HUANG Y,HUANG C S,WU J,et al.Research progress on bioactive substances of mulberry resources and their application in food field [J].Food and Fermentation Industries,2023,49(23):362-370.
[6] 刘静波,陈晶晶,王二雷.黄酮苷元类化合物制备技术及功能活性研究进展 [J].中国食品学报,2018,18(10):276-285.LIU J B,CHEN J J,WANG E L.Research progress in preparation technologies and functional activities of flavonoid aglycone compounds [J].Journal of Chinese Institute of Food Science and Technology,2018,18(10):276-285.
[7] JIA D S,TIAN X,CHEN Y T,et al.Preparation of enzymatic hydrolysates of mulberry leaf flavonoids and investigation into its treatment and mechanism for zebrafish inflammatory bowel disease [J].Fish & Shellfish Immunology,2024,154:109960.
[8] KYZAR E,STEWART A M,LANDSMAN S,et al.Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish [J].Brain Research,2013,1 527:108-116.
[9] MARCON M,HERRMANN A P,MOCELIN R,et al.Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam,fluoxetine and nortriptyline[J].Psychopharmacology,2016,233(21/22):3 815-3 824.
[10] LACHOWICZ J,NIEDZIAŁEK K,ROSTKOWSKA E,et al.Zebrafish as an animal model for testing agents with antidepressant potential [J].Life,2021,11(8):792.
[11] GE C J,WANG S L,WU X Q,et al.Quercetin mitigates depression-like behavior via the suppression of neuroinflammation and oxidative damage in corticosterone-induced mice [J].Journal of Chemical Neuroanatomy,2023,132:102313.
[12] BANSAL Y,SINGH R,SAROJ P,et al.Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression [J].Toxicology and Applied Pharmacology,2018,355:257-268.
[13] ZHU Q,HAN Y S,HE Y,et al.Kaempferol improves breast cancer-related depression through the COX -2/PGE 2 pathway[J].Frontiers in Bioscience,2023,28(11):311.
[14] GOPNAR V V,RAKSHIT D,BANDAKINDA M,et al.Fisetin attenuates arsenic and fluoride subacute co-exposure induced neurotoxicity via regulating TNF -α mediated activation of NLRP 3 inflammasome [J].NeuroToxicology,2023,97:133-149.
[15] ZHANG L,LIU C,YUAN M.Eriodictyol produces antidepressant-like effects and ameliorates cognitive impairments induced by chronic stress [J].Neuroreport,2020,31(15):1 111-1 120.
[16] AMIN F,IBRAHIM M A A,RIZWAN-UL-HASAN S,et al.Interactions of apigenin and safranal with the 5HT1A and 5HT2A receptors and behavioral effects in depression and anxiety:a molecular docking,lipid-mediated molecular dynamics,and in vivo analysis [J].Molecules,2022,27(24):8 658.
[17] YANG R,YANG X X,ZHANG F.New perspectives of taxifolin in neurodegenerative diseases [J].Current Neuropharmacology,2023,21(10):2 097-2 109.
[18] 薛丽,韩红,张力.桑黄素通过抑制 TXNIP /NLRP 3/Caspase- 1信号通路对脑缺血再灌注大鼠神经元凋亡的影响 [J].天津医药,2023,51(5):487-491.XUE L,HAN H,ZHANG L.Effects of Morin on neuronal apoptosis in cerebral ischemia-reperfusion rats by inhibiting TXNIP /NLRP 3/Caspase- 1 signaling pathway [J].Tianjin Medical Journal,2023,51(5):487-491.
[19] GAMMOH O,QNAIS E Y,ATHAMNEH R Y,et al.Unraveling the potential of isorhamnetin as an adjuvant in depression treatment with escitalopram [J].Current Issues in Molecular Biology,2023,45(9):7 668-7 679.
[20] 郭梦杰,刘云,吴志强,等.南极磷虾油对利血平诱导的斑马鱼抑郁模型的改善作用 [J].食品与机械,2023,39(7):152-156,171.GUO M J,LIU Y,WU Z Q,et al.Improvement of Antarctic krill oil on reserpine induced zebrafish depression model [J].Food & Machinery,2023,39(7):152-156,171.
[21] 胡国俊.丙戊酸钠对慢性不可预知应激诱导斑马鱼抑郁模型的改善作用及机制研究 [D].重庆:西南大学,2022:39.HU G J.The improvement effect and mechanism of valproate sodium on chronic unpredictable stress-induced zebrafish depression model [D].Chongqing:Southwest University,2022:39.
[22] GAHTAN E,TANGER P,BAIER H.Visual prey capture in larval zebrafish is controlled by identified reticulospinal neurons downstream of the tectum [J].The Journal of Neuroscience,2005,25(40):9 294-9 303.
[23] JOËLS M,KARST H,ALFAREZ D,et al.Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus [J].Stress,2004,7(4):221-231.
[24] 王慧敏,秦雪梅,刘晓节.脑—肠交互视域下抑郁症与胃肠疾病共病的中西药调节及其机制研究进展 [J].中草药,2024,55(1):332-343.WANG H M,QIN X M,LIU X J.Modulation of depression and gastrointestinal disease co-morbidity by Chinese and western medicines and its mechanism under perspective of brain-gut interaction [J].Chinese Traditional and Herbal Drugs,2024,55(1):332-343.
[25] 何璎,邹蔓姝,韩远山,等.小胶质细胞活化介导的神经元损伤与抑郁症的研究进展 [J].中国药理学通报,2024,40(1):12-15.HE Y,ZOU M S,HAN Y S,et al.Research progress of neuronal injury mediated by microglial activation and depression [J].Chinese Pharmacological Bulletin,2024,40(1):12-15.
[26] PEHRSON A L,ROBERTS D,KHAWAJA A,et al.The role of serotonin neurotransmission in rapid antidepressant actions[J].Psychopharmacology,2022,239(6):1 823-1 838.
[27] 邓淑怡,王佳佳,张永平,等.海马改善斑马鱼慢性应激所致抑郁样行为和病理变化的机制 [J].中国药理学通报,2023,39(3):520-525.DENG X Y,WANG J J,ZHANG Y P,et al.Mechanism of seahorse ameliorating depression-like behavioral and pathological changes caused by chronic stress in zebrafish [J].Chinese Pharmacological Bulletin,2023,39(3):520-525.
[28] 陈贝贝,彭志兰,章超桦,等.牡蛎酶解物对慢性不可预知温和应激斑马鱼抑郁行为改善作用研究 [J].食品科学技术学报,2021,39(4):55-63.CHEN B B,PENG Z L,ZHANG C H,et al.Study on improving effect of oyster hydrolysate on depressive behavior of zebrafish under chronic unpredictable mild stress [J].Journal of Food Science and Technology,2021,39(4):55-63.
[29] 张莉,卢仁睿,王慧慧,等.地黄苷 D对皮质酮诱导的 PC-12细胞损伤的保护作用及机制研究 [J].中草药,2022,53(11):3 385-3 393.ZHANG L,LU R R,WANG H H,et al.Protective effect and mechanism of rehmannioside D on PC- 12 cells injury induced by corticosterone [J].Chinese Traditional and Herbal Drugs,2022,53(11):3 385-3 393.
[30] 林洁筠,段阳,龙淼青,等.柴胡疏肝散在抗抑郁治疗中的药效物质与作用机制研究进展 [J].中国实验方剂学杂志,2024,30(10):246-257.LIN J J,DUAN Y,LONG M Q,et al.Pharmacodynamic substances and action mechanisms of Chaihu Shugansan in antidepressant treatment:a review [J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(10):246-257.
[31] LILIANA D,CLAUDIA C,FEDERICO M,et al.Depression,Serotonin and Tryptophan [J].Current Pharmaceutical Design,2016,22(8):949-954.
[32] GONG X L,CHANG R,ZOU J,et al.The role and mechanism of tryptophan-kynurenine metabolic pathway in depression [J].Reviews in the Neurosciences,2023,34(3):313-324.
[33] 胡超,杨蕙,赵洪庆,等.基于代谢组学与网络药理学的百合地黄汤抗抑郁作用机制研究 [J/OL ].中国中药杂志.(2024 -07-16) [2024 -08-12].https://doi.org/10.19540 /j.cnki.cjcmm.20240712.710.HU C,YANG H,ZHAO H Q,et al.Antidepressant mechanism of Baihe Dihuang Decoction based on metabolomics and network pharmacology [J/OL ].China Journal of Chinese Materia Medica.(2024 -07-16) [2024 -08-12].https://doi.org/10.19540 /j.cnki.cjcmm.20240712.710.
[34] JI S,HAN S S,YU L,et al.Jia Wei Xiao Yao San ameliorates chronic stress-induced depression-like behaviors in mice by regulating the gut microbiome and brain metabolome in relation to purine metabolism [J].Phytomedicine,2022,98:153940.
[35] TAKAHASHI T,OTSUGURO K,OHTA T,et al.Adenosine and inosine release during hypoxia in the isolated spinal cord of neonatal rats [J].British Journal of Pharmacology,2010,161(8):1 806-1 816.
[36] 陈佳俊,秦雪梅,杜冠华,等.基于嘌呤能系统及嘌呤代谢的抑郁症发病机制研究进展 [J].药学学报,2021,56(9):2 464-2 471.CHEN J J,QIN X M,DU G H,et al.Advances in the pathogenesis of depression based on purinergic system and purine metabolism [J].Acta Pharmaceutica Sinica,2021,56(9):2 464-2 471.
[37] BIAN X Q,ZHOU N,ZHAO Y R,et al.Identification of proline,1-pyrroline- 5-carboxylate and glutamic acid as biomarkers of depression reflecting brain metabolism using carboxylomics,a new metabolomics method [J].Psychiatry and Clinical Neurosciences,2023,77(4):196-204.
[38] 伍春桃,陈磊,常祥兵,等.白术多糖对抑郁症小鼠动物模型的作用及机制研究 [J].中国药学杂志,2024,59(9):789-800.WU C T,CHEN L,CHANG X B,et al.Effect and mechanism of Atractylodes macrocephala polysaccharide on CUMS mouse models [J].Chinese Pharmaceutical Journal,2024,59(9):789-800.
