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Figueiredo Godoy AC, Frota FF, Araújo LP, Valenti VE, Pereira EDSBM, Detregiachi CRP, Galhardi CM, Caracio FC, Haber RSA, Fornari Laurindo L, Tanaka M, Barbalho SM. Neuroinflammation and Natural Antidepressants: Balancing Fire with Flora. Biomedicines 2025; 13:1129. [PMID: 40426956 DOI: 10.3390/biomedicines13051129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2025] [Revised: 05/02/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Major depressive disorder (MDD) is a major global health concern that is intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, and more acceptable therapeutic techniques. Phytochemicals, i.e., natural antidepressants derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at the same time. Summary: This narrative review synthesizes evidence from preclinical and clinical studies on the efficacy of phytochemicals such as curcumin, polyphenols, flavonoids, and alkaloids in lowering depressed symptoms. Consistent data show that these substances have neuroprotective, anti-inflammatory, and antioxidant properties, altering neuroimmune interactions, reducing oxidative damage, and improving mitochondrial resilience. Particularly, polyphenols and flavonoids have great therapeutic potential because of their capacity to penetrate the blood-brain barrier, inhibit cytokine activity, and encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, the heterogeneity in study designs, phytochemical formulations, and patient demographics highlights the importance of thorough, standardized clinical studies. Conclusions: This review identifies phytochemicals as compelling adjuvant or independent therapies in depression treatment, providing multimodal mechanisms and enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, and integrative therapy approaches is essential. Using phytotherapeutics could considerably improve holistic and customized depression care, encouraging new research routes in integrative neuroscience and clinical psychiatry.
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Affiliation(s)
- Ana Clara Figueiredo Godoy
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Fernanda Fortes Frota
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Larissa Parreira Araújo
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Vitor E Valenti
- Autonomic Nervous System Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-900, SP, Brazil
| | - Eliana de Souza Bastos Mazuqueli Pereira
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Claudia Rucco P Detregiachi
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Cristiano M Galhardi
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Flávia Cristina Caracio
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, SP, Brazil
| | - Rafael S A Haber
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Lucas Fornari Laurindo
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Masaru Tanaka
- Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
| | - Sandra M Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Research Coordinator at UNIMAR Charity Hospital, Marília 17525-902, SP, Brazil
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Hamlbar EP, Mirghafourvand M, Shaseb E, Kamalifard M. The effect of curcumin on postpartum depression and anxiety in primiparous women: a double-blind randomized placebo-controlled clinical trial. BMC Complement Med Ther 2025; 25:157. [PMID: 40281561 PMCID: PMC12023657 DOI: 10.1186/s12906-025-04798-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 01/29/2025] [Indexed: 04/29/2025] Open
Abstract
Postpartum depression and anxiety are common problems in primiparous women, which can negatively affect Maternal-infant bonding and lead to sexual disorders. It's important to prevent and treat these issues, especially since medication options during breastfeeding may be limited. Our study aimed to investigate the effect of curcumin, a natural substance known for its beneficial properties, on postpartum depression and anxiety in primiparous women. A randomized controlled clinical trial was conducted on 96 primiparous women in Tabriz City. Participants were randomly assigned to either the intervention group (n = 48) or the control group (n = 48) using the random block method. The intervention group received curcumin capsules with a dose of 500 mg, while the control group received a placebo with the same dose once daily for eight weeks. Data was collected using the Edinburgh Postnatal Depression Scale (EPDS) and postpartum-specific Anxiety Scale research short-form (PSAS-RSF) questionnaires. After the intervention, the mean score of depression (mean difference: -2.5; 95% confidence interval: -3.3 to -1.7; P < 0.001) and anxiety (Mean difference: -1.4; 95% confidence interval: -2.1 to -0.7; P < 0.001) in the intervention group were significantly lower than the control group. It seems that curcumin can improve the mental health and quality of life of primiparous women postpartum due to its efficacy in reducing postpartum anxiety and depression, easy accessibility, and cost-effectiveness.
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Affiliation(s)
- Elham Pishevar Hamlbar
- Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mojgan Mirghafourvand
- Social Determinants of Health Research Center, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elnaz Shaseb
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahin Kamalifard
- Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran.
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Shen CL, Hassan T, Presto P, Payberah D, Devega R, Wakefield S, Dunn DM, Neugebauer V. Novel Insights into Dietary Bioactive Compounds and Major Depressive Disorders: Evidence from Animal Studies and Future Perspectives. J Nutr 2025:S0022-3166(25)00190-7. [PMID: 40274236 DOI: 10.1016/j.tjnut.2025.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/25/2025] [Accepted: 04/08/2025] [Indexed: 04/26/2025] Open
Abstract
Clinical depression, including major depressive disorder (MDD), is a chronic mental illness characterized by persistent sadness and indifference. Depression is associated with neuroinflammation, oxidative stress, and neuronal apoptosis in the brain, resulting in microglial overactivation, decreased neuronal and glial proliferation, monoamine depletion, structural abnormalities, and aberrant biochemical activity via the hypothalamic-pituitary-adrenal axis. Recent studies have exhibited the role of dietary bioactive compounds in the mitigation of MDD progression. Here, in this narrative review, we reported the effects of commonly consumed bioactive compounds (curcumin, saffron, garlic, resveratrol, omega-3 fatty acids, ginger, blueberry, tea, and creatine) on MDD and MDD-related neuroinflammation and oxidative stress. The evidence reviewed here is almost exclusively from animal studies and strongly suggests that these commonly consumed bioactive compounds have anti-MDD effects as shown in antidepression-like behaviors, such as increased immobility, sucrose preference, and social interaction. On the basis of the literature/studies reviewed, the proposed molecular mechanisms include 1) the reduction of neuroinflammation activation and oxidative stress, 2) the enhancement of anti-inflammatory and antioxidant properties, 3) the reduction of monoamine oxidase-A production, and 4) the elevation of brain-derived neurotropic factor and neurogenesis. In the future, dietary bioactive compounds on clinical randomized controlled trials are warranted to confirm the findings of preclinical efficacies using bioactive compounds in individuals with MDD.
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Affiliation(s)
- Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
| | - Taha Hassan
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Peyton Presto
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Daniel Payberah
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Rodan Devega
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Sarah Wakefield
- Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Dale M Dunn
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - Volker Neugebauer
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States
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Huang B, Chen WN, Peng CM, Shen XL, Xue J, Yan CC, Zhong FM. Global trends of purinergic receptors and depression: A bibliometric analysis from 2003 to 2023. World J Psychiatry 2025; 15:102344. [PMID: 39974485 PMCID: PMC11758036 DOI: 10.5498/wjp.v15.i2.102344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 12/01/2024] [Accepted: 12/19/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Depression significantly threatens human health. Purinergic receptors are reported to be associated with depression. However, there is no bibliometric research in this field have been published. AIM To provide some reference for the further research in the field of purinergic receptors and depression utilizing bibliometric analysis. METHODS Relevant researches were retrieved from the Web of Science Core Collection database. The period of the search was from January 1, 2003 to December 31, 2023. The CiteSpace (6.2.R7) and VOSviewer (1.6.19) were applied to identify the main contributors of countries, authors, institutions, references and journals. Besides, we evaluate keywords to assess the hotspots and trends over the previous 2 decades. RESULTS Totally, 247 articles were identified, showing an increasing trend over time. The most productive country, institution, and journal in this field are China, Harvard University, and Biological Psychiatry, respectively. Liang SD and Rodrigues, Ana Lucia S were the most prolific authors. Burnstock G ranked first among the cited authors. The cooperation among countries and disciplines is crucial. The P2X7 receptor provides promising prospects for treating depression and further studies are warranted to validate the scope and significance of depression therapeutic strategies. CONCLUSION This study provides an overview of the worldwide research status and future trends in purinergic receptors and depression. P2X7 receptor is considered an appropriate target for the treatment of depression, as well as neurological diseases. It is implied that based on purinergic system, the future prospects for interventions aimed at depression treatment are promising, showing the way for both augmentation strategies and new drug treatments in the context of the pharmacology of depression.
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Affiliation(s)
- Biao Huang
- Department of Acupuncture, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
| | - Wei-Ning Chen
- Graduate School, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Chun-Mei Peng
- Department of Asset Management, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiu-Li Shen
- Department of Gastroenterology, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
| | - Jin Xue
- Graduate School, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Chun-Chuan Yan
- Department of Acupuncture, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi Province, China
| | - Fa-Ming Zhong
- Department of Spinal Surgery, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China
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5
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Zhao R, Wang J, Chung SK, Xu B. New insights into anti-depression effects of bioactive phytochemicals. Pharmacol Res 2025; 212:107566. [PMID: 39746497 DOI: 10.1016/j.phrs.2024.107566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 12/04/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025]
Abstract
Depression is one of the most common psychological disorders, and due to its high prevalence and mortality rates, it imposes a significant disease burden. Contemporary treatments for depression involve various synthetic drugs, which have limitations such as side effects, single targets, and slow onset of action. Unlike synthetic medications, phytochemicals offer the benefits of a multi-target and multi-pathway mode of treatment for depression. In this literature review, we describe the pharmacological actions, experimental models, and clinical trials of the antidepressant effects of various phytochemicals. Additionally, we summarize the potential mechanisms by which these phytochemicals prevent depression, including regulating neurotransmitters and their receptors, the HPA axis, inflammatory responses, managing oxidative stress, neuroplasticity, and the gut microbiome. Phytochemicals exert therapeutic effects through multiple pathways and targets, making traditional Chinese medicine (TCM) a promising adjunctive antidepressant for the prevention, alleviation, and treatment of depression. Therefore, this review aims to provide robust evidence for subsequent research into developing phytochemical resources as effective antidepressant agents.
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Affiliation(s)
- Ruohan Zhao
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China
| | - Jingwen Wang
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China
| | - Sookja Kim Chung
- Faculty of Medicine, Macau University of Science and Technology, Macau, China.
| | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China.
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Picheta N, Piekarz J, Daniłowska K, Mazur K, Piecewicz - Szczęsna H, Smoleń A. Phytochemicals in the treatment of patients with depression: a systemic review. Front Psychiatry 2024; 15:1509109. [PMID: 39717381 PMCID: PMC11663887 DOI: 10.3389/fpsyt.2024.1509109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 11/19/2024] [Indexed: 12/25/2024] Open
Abstract
Background Depression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous - currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda. Materials and methods The study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta - analysis were included in the systematic review. Results Many plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient. Conclusions Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients' quality of life and reduce treatment costs.
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Affiliation(s)
- Natalia Picheta
- Chair and Department of Epidemiology and Clinical Research Methodology, Medical
University of Lublin, Lublin, Poland
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Seo CR, Lee BK, Jee HJ, Yoo JR, Lee CK, Park JW, Jung YS. Ameliorating Effect of Fermented Perilla frutescens on Sleep Deprivation-Induced Cognitive Impairment Through Antioxidant and BDNF Signaling in Mice. Nutrients 2024; 16:4224. [PMID: 39683616 DOI: 10.3390/nu16234224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 12/03/2024] [Accepted: 12/05/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Adequate sleep is essential for maintaining cognitive function, as evidenced by literature. Perilla frutescens var. acuta Kudo (PF) is a traditional medicinal herb reported to improve vascular cognitive impairment and induce sedation. However, the effects of PF on cognitive impairment caused by sleep deprivation (SD) have not yet been evaluated. This study aims to evaluate the effects of fermented PF (FPF) and its underlying mechanisms in a model of SD-induced cognitive impairment. Methods: Mice were subjected to SD to establish cognitive impairment, and FPF was administered once daily for 3 days. Cognitive performance was assessed using Y-maze and passive avoidance tests, followed by molecular mechanisms analyses. Results: FPF treatment improved SD-induced cognitive impairment, as evidenced by increased spontaneous alternation and extended latency time. Histological analysis revealed that SD impaired the hippocampus, and this impairment was alleviated by FPF treatment. FPF demonstrated antioxidant activity by increasing glutathione levels and decreasing malondialdehyde levels. Furthermore, the decreased levels of brain-derived neurotrophic factor (BDNF) observed in sleep-deprived mice were restored with FPF treatment. FPF also enhanced the phosphorylation of tropomyosin receptor kinase B, extracellular signal-regulated kinase, and cAMP response element-binding protein. Conclusions: These results indicate that FPF may have beneficial effects on SD-induced cognitive impairment by protecting against oxidative stress and increasing BDNF expression.
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Affiliation(s)
- Chae-Ryeong Seo
- Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
| | - Bo Kyung Lee
- Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
| | - Hye Jin Jee
- Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
| | - Jae Ryeong Yoo
- Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
| | - Chul-Kyu Lee
- Headquarters of New Drug Development Support, Corestemchemon Inc., 15 F, Gyeonggi Bio Center, Suwon 16229, Republic of Korea
| | - Jin Wook Park
- Headquarters of New Drug Development Support, Corestemchemon Inc., 15 F, Gyeonggi Bio Center, Suwon 16229, Republic of Korea
| | - Yi-Sook Jung
- Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
- Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 16499, Republic of Korea
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Guo P, Wang Z, Sun L, He Z, Li J, Geng J, Zong Y, Chen W, Du R. 20 (S)-Protopanaxadiol Alleviates DRP1-Mediated Mitochondrial Dysfunction in a Depressive Model In Vitro and In Vivo via the SIRT1/PGC-1α Signaling Pathway. Molecules 2024; 29:5085. [PMID: 39519726 PMCID: PMC11547436 DOI: 10.3390/molecules29215085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/11/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Depression is a complex and common mental illness affecting physical and psychological health. Panax ginseng C. A. Mey is a traditional Chinese medicine with abundant pharmacological activity and applications in regulating mood disorders. 20 (S)-Protopanaxadiol is the major intestinal metabolite of ginsenoside and one of the active components in ginseng. In this study, we aimed to investigate the therapeutic effects of 20 (S)-Protopanaxadiol on neuronal damage and depression, which may involve mitochondrial dynamics. However, the mechanism underlying the antidepressant effects of 20 (S)-Protopanaxadiol is unelucidated. In the present study, we investigated the potential mechanisms underlying the antidepressant activity of 20 (S)-Protopanaxadiol by employing a corticosterone-induced HT22 cellular model and a chronic unpredicted mild stress (CUMS)-induced animal model in combination with a network pharmacology approach. In vitro, the results showed that 20 (S)-Protopanaxadiol ameliorated the corticosterone (CORT)-induced decrease in HT22 cell viability, decrease in 5-hydroxytryptamine (5-HT) levels, and increase in nitric oxide (NO) and malondialdehyde (MDA) levels. Furthermore, 20 (S)-Protopanaxadiol exerted improvement effects on the CORT-induced increase in HT22 cell mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and apoptosis. In vivo, the results showed that 20 (S)-Protopanaxadiol ameliorated depressive symptoms and hippocampal neuronal damage in CUMS mice, and sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-1-Alpha (PGC-1α) activity were activated in the hippocampus of mice, thereby alleviating mitochondrial dysfunction and promoting the clearance of damaged mitochondria. In both in vivo and in vitro models, after inhibiting SIRT1 expression, the protective effect of 20 (S)-Protopanaxadiol on mitochondria was significantly weakened, and dynamin-related protein 1 (DRP1)-mediated mitochondrial division was significantly reduced. These findings suggest that 20 (S)-Protopanaxadiol may exert neuroprotective and antidepressant effects by attenuating DRP1-mediated mitochondrial dysfunction and apoptosis by modulating the SIRT1/PGC-1α signaling pathway.
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Affiliation(s)
- Pengli Guo
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
| | - Zixian Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
| | - Li Sun
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
| | - Zhongmei He
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
| | - Jianming Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
| | - Jianan Geng
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
| | - Ying Zong
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
| | - Weijia Chen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
| | - Rui Du
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (P.G.)
- Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China
- Key Laboratory of Animal Production and Product Quality and Security, Ministry of Educatio, Ministry of National Education, Changchun 130118, China
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Guo N, Wang X, Xu M, Bai J, Yu H, Le Zhang. PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression. Pharmacol Res 2024; 206:107300. [PMID: 38992850 DOI: 10.1016/j.phrs.2024.107300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/13/2024]
Abstract
Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of depression is complex and involves multiple signal transduction pathways and molecular changes. The PI3K/AKT pathway is an essential signaling pathways in neurons, which is widely expressed in emotion-related regions of the brain. Therefore, the PI3K/AKT pathway may play a moderating role in mood disorders. However, the role and mechanism of the PI3K/AKT signaling pathway in depression have not been fully described. This review systematically summarized the role of the PI3K/AKT signaling pathway in the pathogenesis of depression and discussed its potential in the treatment of depression. This will help in the treatment of depression and the development of antidepressants.
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Affiliation(s)
- Ningning Guo
- School of Mental Health, Jining Medical University, Jining, China
| | - Xin Wang
- Department of Radiation Therapy, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Muran Xu
- Clinical College, Jining Medical University, Jining, China
| | - Jie Bai
- Medical School, Kunming University of Science and Technology, Kunming, China.
| | - Hao Yu
- School of Mental Health, Jining Medical University, Jining, China.
| | - Le Zhang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
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Su L, Lu H, Zhang D, Zhu X, Li J, Zong Y, Zhao Y, He Z, Chen W, Du R. Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155519. [PMID: 38492365 DOI: 10.1016/j.phymed.2024.155519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 02/07/2024] [Accepted: 03/07/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1β, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.
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Affiliation(s)
- Lili Su
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Haoyu Lu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Dongxue Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Xiaoying Zhu
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Jianming Li
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Ying Zong
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Yan Zhao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Zhongmei He
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China
| | - Weijia Chen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China.
| | - Rui Du
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Changchun 130118, China; Key Laboratory of Animal Production and Product Quality and Security, Ministry of Education, Ministry of National Education, Changchun 130118, China.
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Yang Y, Chen YK, Xie MZ. Exploring the transformative impact of traditional Chinese medicine on depression: Insights from animal models. World J Psychiatry 2024; 14:607-623. [PMID: 38808079 PMCID: PMC11129158 DOI: 10.5498/wjp.v14.i5.607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/06/2024] [Accepted: 04/28/2024] [Indexed: 05/16/2024] Open
Abstract
Depression, a prevalent and complex mental health condition, presents a significant global health burden. Depression is one of the most frequent mental disorders; deaths from it account for 14.3% of people worldwide. In recent years, the integration of complementary and alternative medicine, including traditional Chinese medicine (TCM), has gained attention as a potential avenue for addressing depression. This comprehensive review critically assesses the efficacy of TCM interventions in alleviating depressive symptoms. An in-depth look at different research studies, clinical trials, and meta-analyses is used in this review to look into how TCM practices like herbal formulations, acupuncture, and mind-body practices work. The review looks at the quality of the evidence, the rigor of the methods, and any possible flaws in the current studies. This gives us an idea of where TCM stands right now in terms of treating depression. This comprehensive review aims to assess the efficacy of TCM interventions in alleviating depressive symptoms. In order to learn more about their possible healing effects, the study also looks into how different types of TCM work, such as herbal formulas, acupuncture, and mind-body practices.
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Affiliation(s)
- Yan Yang
- School of Nursing, Hunan University of Chinese Medicine, Changsha 410200, Hunan Province, China
| | - Yan-Kun Chen
- Precision Medicine R&D Center, Zhuhai Institute of Advanced Technology, Chinese Academy of Sciences, Zhuhai 519000, Guangdong Province, China
- School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410200, Hunan Province, China
| | - Meng-Zhou Xie
- School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410200, Hunan Province, China
- Hunan Engineering Technology Research Center for Medicinal and Functional Food, Hunan University of Chinese Medicine, Changsha 410200, Hunan Province, China
- Key Laboratory of TCM Heart and Lung Syndrome Differentiation and Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha 410200, Hunan Province, China
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12
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Wang H, Jia R, Zhang M, Fan W. The influence of stress on mental health among Chinese college students: The moderating role of psychological suzhi. Heliyon 2024; 10:e26699. [PMID: 38444499 PMCID: PMC10912246 DOI: 10.1016/j.heliyon.2024.e26699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 02/08/2024] [Accepted: 02/19/2024] [Indexed: 03/07/2024] Open
Abstract
Depending on its duration, stress can be divided into chronic and acute stress, both of which can be detrimental to an individual's mental health. Psychological suzhi may act as a protective factor that buffers the adverse effects of stress. This study aimed to explore the moderating role of psychological suzhi in the relationship between these two types of stress and mental health based on a dual-factor model of mental health. Study 1 explored the moderating role of psychological suzhi on the relationship between chronic stress and mental health using the Adolescent Self-Rating Life Events Check List, College Student Psychological Suzhi Scale Brief Mental Health Version, Satisfaction With Life Scale, and 12-item General Health Questionnaire to investigate 919 Chinese college students. A hierarchical regression model was used to examine the moderating effects. Study 2 examined the moderating role of psychological suzhi on the relationship between acute stress and mental health. Participants (N = 56) were classified into high (N = 30) and low (N = 26) psychological suzhi groups based on the Psychological Suzhi Scale. They completed the Trier Social Stress Test for Groups and a specific control condition, and their state anxiety and happiness levels were assessed. Data were analyzed using a mixed-design repeated-measures ANOVA. The results of Study 1 revealed that psychological suzhi moderated the influence of chronic stress on the negative indicator of mental health (psychological symptoms) (β = -0.18, t = -6.90, p < 0.001). The results of Study 2 showed that psychological suzhi moderated the effect of acute stress on the negative indicator of mental health (state anxiety) [F (1, 54) = 4.79, p < 0.05, η2 = 0.08]. Psychological suzhi can moderate the influence of both chronic and acute stress on the negative indicators of college students' mental health but cannot moderate the influence on the positive indicators of mental health.
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Affiliation(s)
- Huixin Wang
- Department of Applied Psychology, Binzhou Medical University, Yantai, China
| | - Ruxue Jia
- Psychological Center, Xinghua Fourth People's Hospital, Taizhou , China
| | - Min Zhang
- Department of Applied Psychology, Binzhou Medical University, Yantai, China
| | - Wenyi Fan
- Department of Applied Psychology, Binzhou Medical University, Yantai, China
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Zhang R, Zeng M, Zhang X, Zheng Y, Lv N, Wang L, Gan J, Li Y, Jiang X, Yang L. Therapeutic Candidates for Alzheimer's Disease: Saponins. Int J Mol Sci 2023; 24:10505. [PMID: 37445682 DOI: 10.3390/ijms241310505] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/20/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Drug development for Alzheimer's disease, the leading cause of dementia, has been a long-standing challenge. Saponins, which are steroid or triterpenoid glycosides with various pharmacological activities, have displayed therapeutic potential in treating Alzheimer's disease. In a comprehensive review of the literature from May 2007 to May 2023, we identified 63 references involving 40 different types of saponins that have been studied for their effects on Alzheimer's disease. These studies suggest that saponins have the potential to ameliorate Alzheimer's disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. Most intriguingly, ginsenoside Rg1 and pseudoginsenoside-F11 possess these important pharmacological properties and show the best promise for the treatment of Alzheimer's disease. This review provides a summary and classification of common saponins that have been studied for their therapeutic potential in Alzheimer's disease, showcasing their underlying mechanisms. This highlights the promising potential of saponins for the treatment of Alzheimer's disease.
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Affiliation(s)
- Ruifeng Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Miao Zeng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiaolu Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yujia Zheng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Nuan Lv
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Luming Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Jiali Gan
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yawen Li
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xijuan Jiang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Lin Yang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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14
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Shen J, Wang Q, Mao Y, Gao W, Duan S. Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies. MedComm (Beijing) 2023; 4:e288. [PMID: 37256211 PMCID: PMC10225743 DOI: 10.1002/mco2.288] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 04/25/2023] [Accepted: 05/08/2023] [Indexed: 06/01/2023] Open
Abstract
Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling-targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor-promoting role by blocking the mitochondria-dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.
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Affiliation(s)
- Jinze Shen
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang ProvinceSchool of MedicineHangzhou City UniversityHangzhouZhejiangChina
| | - Qurui Wang
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang ProvinceSchool of MedicineHangzhou City UniversityHangzhouZhejiangChina
| | - Yunan Mao
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang ProvinceSchool of MedicineHangzhou City UniversityHangzhouZhejiangChina
| | - Wei Gao
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang ProvinceSchool of MedicineHangzhou City UniversityHangzhouZhejiangChina
| | - Shiwei Duan
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang ProvinceSchool of MedicineHangzhou City UniversityHangzhouZhejiangChina
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Liu X, Huang R, Wan J. Puerarin: a potential natural neuroprotective agent for neurological disorders. Biomed Pharmacother 2023; 162:114581. [PMID: 36966665 DOI: 10.1016/j.biopha.2023.114581] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/18/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Puerarin is an isoflavone compound derived from Pueraria lobata in traditional Chinese medicine. Accumulating evidence has indicated that puerarin demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Based on the latest research progress on puerarin as a neuroprotective agent, its pharmacological activity, molecular mechanism, and therapeutic application were systematically reviewed with emphasis on pre-clinical studies. The related information was extracted and compiled from major scientific databases, including PubMed, ScienceDirect, SpringerLink, and Chinese National Knowledge Infrastructure, using 'Puerarin', 'Neuroprotection', 'Apoptosis', 'Autophagy', 'Antioxidant', 'Mitochondria', 'Anti-inflammation' as keywords. This review complied with The Preferred Reporting Items for Systematic Reviews criteria. Forty-three articles met established inclusion and exclusion criteria. Puerarin has shown neuroprotective effects against a variety of neurological disorders, including ischemic cerebrovascular disease, subarachnoid hemorrhage, epilepsy, cognitive disorders, traumatic brain injury, Parkinson's disease, Alzheimer's disease, anxiety, depression, diabetic neuropathy, and neuroblastoma/glioblastoma. Puerarin demonstrates anti-apoptosis, proinflammatory mediator inhibitory, autophagy regulatory, anti-oxidative stress, mitochondria protection, Ca2+ influx inhibitory, and anti-neurodegenerative activities. Puerarin exerts noticeable neuroprotective effects on various models of neurological disorders in vivo (animal). This review will contribute to the development of puerarin as a novel clinical drug candidate for the treatment of neurological disorders. However, well-designed, high-quality, large-scale, multicenter randomized clinical studies are needed to determine the safety and clinical utility of puerarin in patients with neurological disorders.
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Affiliation(s)
- Xue Liu
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Rui Huang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jiye Wan
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
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Zhang YM, Wei RM, Li XY, Feng YZ, Zhang KX, Ge YJ, Kong XY, Liu XC, Chen GH. Long-term environmental enrichment overcomes depression, learning, and memory impairment in elderly CD-1 mice with maternal sleep deprivation exposure. Front Aging Neurosci 2023; 15:1177250. [PMID: 37168717 PMCID: PMC10164971 DOI: 10.3389/fnagi.2023.1177250] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/03/2023] [Indexed: 05/13/2023] Open
Abstract
Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.
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Affiliation(s)
- Yue-Ming Zhang
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ru-Meng Wei
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xue-Yan Li
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yi-Zhou Feng
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Kai-Xuan Zhang
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yi-Jun Ge
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiao-Yi Kong
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xue-Chun Liu
- Department of Neurology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China
- *Correspondence: Gui-Hai Chen, ; Xue-Chun Liu,
| | - Gui-Hai Chen
- Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui, China
- *Correspondence: Gui-Hai Chen, ; Xue-Chun Liu,
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