{"title":"印度芥蜜的植物成分通过激活海马中的TrkB/CREB/BDNF通路，对利血平诱导的抑郁状态具有抗抑郁活性。","authors":"Saakshi Saini, Viney Kumar, Samrat Chauhan, Rajat Saini, Partho Biswas, Tiyasa Pathak, Thakur Gurjeet Singh, Surendra Kumar Saini, Kaushik Ghosh, Prabhat Kumar, Partha Roy","doi":"10.1080/1028415X.2025.2554363","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Depression is a global health issue, with traditional antidepressants raising safety concerns. Indian mustard honey (MH) offers a potential alternative due to its health benefits, though its antidepressant effects remain unexplored. This study investigates the neuroprotective and antidepressant effects of MH in HT-22 cells <i>in vitro</i> and in Wistar rats <i>in vivo</i>.</p><p><strong>Methods: </strong>Chemical constituents of MH were identified using liquid chromatography-mass spectrometry (LC-MS). Effects of MH on phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotropic factor (BDNF) and phosphorylated cyclic AMP-dependent response element-binding protein (p-CREB) were assessed in reserpine-treated HT-22 cells and rat models. Antidepressant effects in rats were evaluated using forced swim, tail suspension and locomotor activity tests, along with hippocampal histopathology and molecular analyses.</p><p><strong>Results: </strong>MH profiling identified key polyphenols with antioxidant properties. In HT-22 cells, MH showed neuroprotection at 60 mg/mL (<i>p</i> < 0.001), and upregulated p-TrkB, BDNF, and p-CREB (<i>p</i> < 0.001) against reserpine-induced oxidative stress. In rats, compared to fluoxetine, MH at 1 g/kg BW increased locomotor activity by ∼2.3 fold and reduced immobility by ∼50% and 25% in the tail suspension and forced swim tests (<i>p</i> < 0.001), respectively, showing comparable/ better antidepressant effects. It also preserved hippocampal architecture and upregulated p-TrkB, BDNF, and p-CREB (<i>p</i> < 0.001) levels compared to reserpine-treated rats.</p><p><strong>Discussions: </strong>MH demonstrated antioxidant, neuroprotective and antidepressant activities in <i>in vitro</i> and <i>in vivo</i> models, suggesting therapeutic potential. However, further studies on additional pathways, including β-catenin/Wnt, MAPK/ERK, along with pharmacokinetics, are essential before recommending MH as an antidepressant agent.</p>","PeriodicalId":19423,"journal":{"name":"Nutritional Neuroscience","volume":" ","pages":"1-18"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phytoconstituents of Indian mustard honey impart antidepressant activity in reserpine-induced depressed condition through activation of TrkB/CREB/BDNF pathway in hippocampus.\",\"authors\":\"Saakshi Saini, Viney Kumar, Samrat Chauhan, Rajat Saini, Partho Biswas, Tiyasa Pathak, Thakur Gurjeet Singh, Surendra Kumar Saini, Kaushik Ghosh, Prabhat Kumar, Partha Roy\",\"doi\":\"10.1080/1028415X.2025.2554363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Depression is a global health issue, with traditional antidepressants raising safety concerns. Indian mustard honey (MH) offers a potential alternative due to its health benefits, though its antidepressant effects remain unexplored. This study investigates the neuroprotective and antidepressant effects of MH in HT-22 cells <i>in vitro</i> and in Wistar rats <i>in vivo</i>.</p><p><strong>Methods: </strong>Chemical constituents of MH were identified using liquid chromatography-mass spectrometry (LC-MS). Effects of MH on phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotropic factor (BDNF) and phosphorylated cyclic AMP-dependent response element-binding protein (p-CREB) were assessed in reserpine-treated HT-22 cells and rat models. Antidepressant effects in rats were evaluated using forced swim, tail suspension and locomotor activity tests, along with hippocampal histopathology and molecular analyses.</p><p><strong>Results: </strong>MH profiling identified key polyphenols with antioxidant properties. In HT-22 cells, MH showed neuroprotection at 60 mg/mL (<i>p</i> < 0.001), and upregulated p-TrkB, BDNF, and p-CREB (<i>p</i> < 0.001) against reserpine-induced oxidative stress. In rats, compared to fluoxetine, MH at 1 g/kg BW increased locomotor activity by ∼2.3 fold and reduced immobility by ∼50% and 25% in the tail suspension and forced swim tests (<i>p</i> < 0.001), respectively, showing comparable/ better antidepressant effects. It also preserved hippocampal architecture and upregulated p-TrkB, BDNF, and p-CREB (<i>p</i> < 0.001) levels compared to reserpine-treated rats.</p><p><strong>Discussions: </strong>MH demonstrated antioxidant, neuroprotective and antidepressant activities in <i>in vitro</i> and <i>in vivo</i> models, suggesting therapeutic potential. However, further studies on additional pathways, including β-catenin/Wnt, MAPK/ERK, along with pharmacokinetics, are essential before recommending MH as an antidepressant agent.</p>\",\"PeriodicalId\":19423,\"journal\":{\"name\":\"Nutritional Neuroscience\",\"volume\":\" \",\"pages\":\"1-18\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nutritional Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1028415X.2025.2554363\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutritional Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1028415X.2025.2554363","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
目的：抑郁症是一个全球性的健康问题，传统的抗抑郁药引起了安全性担忧。印度芥末蜂蜜（MH）提供了一种潜在的替代品，因为它对健康有益，尽管它的抗抑郁作用尚未被探索。本研究探讨了MH对HT-22细胞和Wistar大鼠体内的神经保护和抗抑郁作用。方法：采用液相色谱-质谱联用技术对其化学成分进行鉴定。在利血平处理的HT-22细胞和大鼠模型中，评估了MH对磷酸化酪氨酸激酶受体B （p-TrkB）、脑源性神经营养因子（BDNF）和磷酸化环amp依赖性反应元件结合蛋白（p-CREB）的影响。通过强迫游泳、悬尾和运动活动测试，以及海马组织病理学和分子分析来评估大鼠的抗抑郁作用。结果：MH谱分析鉴定出具有抗氧化性能的关键多酚。在HT-22细胞中，60 mg/mL (p p p p p) MH显示出神经保护作用。讨论：MH在体外和体内模型中显示出抗氧化、神经保护和抗抑郁活性，提示治疗潜力。然而，在推荐MH作为抗抑郁药物之前，有必要进一步研究其他途径，包括β-catenin/Wnt、MAPK/ERK以及药代动力学。
Phytoconstituents of Indian mustard honey impart antidepressant activity in reserpine-induced depressed condition through activation of TrkB/CREB/BDNF pathway in hippocampus.
Objective: Depression is a global health issue, with traditional antidepressants raising safety concerns. Indian mustard honey (MH) offers a potential alternative due to its health benefits, though its antidepressant effects remain unexplored. This study investigates the neuroprotective and antidepressant effects of MH in HT-22 cells in vitro and in Wistar rats in vivo.
Methods: Chemical constituents of MH were identified using liquid chromatography-mass spectrometry (LC-MS). Effects of MH on phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotropic factor (BDNF) and phosphorylated cyclic AMP-dependent response element-binding protein (p-CREB) were assessed in reserpine-treated HT-22 cells and rat models. Antidepressant effects in rats were evaluated using forced swim, tail suspension and locomotor activity tests, along with hippocampal histopathology and molecular analyses.
Results: MH profiling identified key polyphenols with antioxidant properties. In HT-22 cells, MH showed neuroprotection at 60 mg/mL (p < 0.001), and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) against reserpine-induced oxidative stress. In rats, compared to fluoxetine, MH at 1 g/kg BW increased locomotor activity by ∼2.3 fold and reduced immobility by ∼50% and 25% in the tail suspension and forced swim tests (p < 0.001), respectively, showing comparable/ better antidepressant effects. It also preserved hippocampal architecture and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) levels compared to reserpine-treated rats.
Discussions: MH demonstrated antioxidant, neuroprotective and antidepressant activities in in vitro and in vivo models, suggesting therapeutic potential. However, further studies on additional pathways, including β-catenin/Wnt, MAPK/ERK, along with pharmacokinetics, are essential before recommending MH as an antidepressant agent.
期刊介绍：
Nutritional Neuroscience is an international, interdisciplinary broad-based, online journal for reporting both basic and clinical research in the field of nutrition that relates to the central and peripheral nervous system. Studies may include the role of different components of normal diet (protein, carbohydrate, fat, moderate use of alcohol, etc.), dietary supplements (minerals, vitamins, hormones, herbs, etc.), and food additives (artificial flavours, colours, sweeteners, etc.) on neurochemistry, neurobiology, and behavioural biology of all vertebrate and invertebrate organisms. Ideally this journal will serve as a forum for neuroscientists, nutritionists, neurologists, psychiatrists, and those interested in preventive medicine.
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