The quercetin-serotonin transporter (SERT) connection: a new hope for depression therapy?

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-09-04 DOI:10.1007/s00213-025-06889-6

Meesala Krishna Murthy

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Abstract

Quercetin, a naturally occurring flavonoid, has been found to be a potential agent for the treatment of major depressive disorder (MDD), given the complexity of its interaction with the serotonin transporter (SERT). Clinically, quercetin has direct and indirect modulatory effects as opposed to conventional selective serotonin reuptake inhibitors (SSRI), which act mainly by inhibiting SERT after a time delay and communicate with SERT through possible binding location preferences and allosteric processing, while simultaneously controlling its definite expression through anti-inflammatory and antioxidant pathways, such as the NF-kB, AMPK/SIRT-1, and Nrf2-ARE cascades. These processes assist in modifying serotonergic neurotransmission and minimizing oxidative and inflammatory strains, which are the major contributors to the pathophysiology of depression. Quercetin positively affects neuroplasticity and regulates the gut-to-brain axis, which affirms its antidepressant effects. Preclinical evidence indicates that quercetin can cause more rapid and extensive effects than SSRIs. However, translation issues include poor bioavailability and interindividual variation. Future trials should focus on inflammatory markers and individual quercetin formulations to maximize therapeutic effects in the depressed state.

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槲皮素-血清素转运体（SERT）连接：抑郁症治疗的新希望？

槲皮素是一种天然存在的类黄酮，由于其与血清素转运体（SERT）相互作用的复杂性，已被发现是治疗重度抑郁症（MDD）的潜在药物。与传统的选择性5 -羟色胺再摄取抑制剂（SSRI）相比，槲皮素在临床上具有直接和间接的调节作用，后者主要通过延迟时间抑制SERT，并通过可能的结合位置偏好和变构加工与SERT沟通，同时通过NF-kB、AMPK/SIRT-1和Nrf2-ARE级联等抗炎和抗氧化途径控制其明确表达。这些过程有助于改变血清素能神经传递，减少氧化和炎症菌株，这是抑郁症病理生理的主要贡献者。槲皮素积极影响神经可塑性，调节肠-脑轴，这证实了它的抗抑郁作用。临床前证据表明，槲皮素的作用比SSRIs更迅速、更广泛。然而，翻译问题包括生物利用度差和个体间变异。未来的试验应该关注炎症标志物和个体槲皮素配方，以最大限度地提高抑郁状态下的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.