INFLAMMOPHARMACOLOGY
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2026
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IF 6.3
Yang Xiaoxiao,Yang Nengjie,Wang Yunan,Xiao Jun,Gu Zhifeng,Dong Chen
Background Sjogren’s Syndrome (SS) is an autoimmune disease characterized mainly by xerostomia (dry mouth), xerophthalmia (dry eyes) and damage of immune system. Recent studies have found that SS patients frequently experience neuropsychiatric symptoms such as depression and fatigue, suggesting potential underlying mechanisms involving complex immune-neural interactions. However, current therapeutic strategies targeting this immune-neuropsychiatric axis remain limited. Agomelatine (AGO), a novel antidepressant classified as a melatonin (MLT) receptor agonist and a 5-HT2C receptor antagonist, has yet to be fully investigated for its immunomodulatory potential and therapeutic application in SS. Objectives This study explores the immune–neuropsychiatric interaction in SS using Non-Obese Diabetic (NOD) mice, and investigates the therapeutic potential of AGO, highlighting its anti-inflammatory and immunomodulatory effects. Methods NOD mice were divided into blank control, hydroxychloroquine (HCQ, a basic immune regulatory drug), MLT, and AGO groups; ICR mice served as healthy controls. All received intraperitoneal injections for 4 weeks. Behavioral tests (open field and tail suspension) were conducted. Flow cytometric analysis was performed to systematically evaluate splenic T cell and B cell subsets. The results showed that only the proportions of T helper 1 (Th1) and T helper 17 (Th17) cells exhibited significant differences, whereas no obvious changes were observed in B cells or regulatory T cells (Tregs).Salivary gland tissues were assessed by Hematoxylin–Eosin (HE) staining for inflammation and damage, and by immunofluorescence for Th1-epithelial cell co-localization. Results AGO-treated mice showed significantly shorter immobility time in the tail suspension test versus untreated NOD controls, indicating reduced despair. AGO intervention also reduced splenic Th1 and Th17 cell proportions, alleviated salivary gland lymphocyte infiltration, and decreased Th1-epithelial cell co-localization, suggesting inhibition of Th1 cell migration to target tissues. Conclusion AGO significantly improved behavioral performance, reduced the proportion of Th1 cells in the spleen, and alleviated inflammatory infiltration in the salivary glands of NOD mice. These findings suggest that the drug may exert therapeutic effects by modulating immune responses and neurobehavioral functions, positioning it as a promising candidate for the treatment of SS.
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Journal of Neuroinflammation
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2022
·Vol. 19
·期 1
·1-14
·
IF 9.587
Lan Tian,Wu Yuhan,Zhang Yulei,Li Shuhan,Zhu Zhanpeng,Wang Liyan,Mao Xueqin,Li Ye,Fan Cuiqin,Wang Wenjing,Yu Shu Yan
Background Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder.
Methods Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Results Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. Conclusion Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine. Graphical Abstract
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Frontiers in Aging Neuroscience
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2022
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IF 5.702
Yang Xiao-bo,Zu Heng-bing,Zhao Yong-fei,Yao Kai
Agomelatine, an agonist of melatonergic MT1 and MT2 receptors and a selective 5-hydroxytryptamine 2C receptor antagonist, is widely applied in treating depression and insomnia symptoms in several neurogenerative diseases. However, the neuroprotective effect of agomelatine in Alzheimer’s disease (AD) is less known. In this study, a total of 30 mice were randomly divided into three groups, namely, wild type (WT), APP/PS1, and agomelatine (50 mg/kg). After 30 days, the Morris water maze was performed to test the cognitive ability of mice. Then, all mice were sacrificed, and the hippocampus tissues were collected for ELISA, Western blot, and immunofluorescence analysis. In this study, we found that agomelatine attenuated spatial memory deficit, amyloid-β (Aβ) deposition, tau phosphorylation, and neuroinflammation in the hippocampus of APP/PS1 mice. Further study demonstrated that agomelatine treatment upregulated the protein expression of DHCR24 and downregulated P-Akt, P-mTOR, p-p70s6k, Hes1, and Notch1 expression. In summary, our results identified that agomelatine could improve cognitive impairment and ameliorate AD-like pathology in APP/PS1 mice via activating DHCR24 signaling and inhibiting Akt/mTOR and Hes1/Notch1 signaling pathway. Agomelatine may become a promising drug candidate in the therapy of AD.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2017
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IF 3.255
Xiujuan Chen,Shuiqing Zheng,Jian Le,Zheyuan Qian,Runsheng Zhang,Zhanying Hong,Yifeng Chai
Antidepressant drugs are widely used in the treatment of different psychiatric disorders, as well as in conjunction with antipsychotics for the treatment of major depressive disorder. In this study, a simple and rapid ultrasound-assisted low-density solvent dispersive liquid–liquid microextraction (UA-LDS-DLLME) method was developed for the simultaneous determination of 12 new antidepressants (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide, melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram, paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood by gas chromatography–mass spectrometry (GC–MS). Different parameters affecting the UA-LDS-DLLME were optimized and the optimal conditions were as follows: 100 μL of toluene as extraction solvent, extraction pH 12 and 3 min of ultrasound stirring. Good linearity ( R 2 ≥ 0.991) was obtained at the concentration range of 15–1500 ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline and citalopram, and 5–500 ng/mL for agomelatine, mirtazapine, moclobemide, N-desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The intra-day and inter-day precision were all less than 10%, and accuracy of intra-day and inter-day were in the range of −12.7% to 7.9% and −13.9 to 11.8%, respectively. The extraction recoveries of most analytes were more than 60%. The UA-LDS-DLLME/GC–MS method was demonstrated with acceptable precision, accuracy and good specificity for the simultaneous determination of 12 antidepressants and 2 antipsychotics, and has been successfully applied in a real case.
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Advanced Science
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2025
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IF 14.1
Wei Zhang,Xingwang Ji,Qianyanqiu Zhao,Jinyao Qi,Wen Guo,Gaoshuo Zhang,Yujing Guan,Shenglong Li,Yuling Mao
Central nervous system (CNS) disorders confront significant challenges in drug delivery due to the blood–brain barrier (BBB). Inspired by the rapid and precise binding of odor molecules to olfactory receptors (ORs), this research uses thiolated HPMA to construct odor nanoparticles (nanoodors) capable of delivering drugs to the CNS via the olfacto–cerebral pathway to overcome the delivery obstruction. The nanoodor core is used to encapsulate agomelatine (AGO), a CNS-targeting antidepressant, and the encapsulation efficiency exceeded 80%. A series of thiol-presenting nanoscale structures with different surface densities of thiol groups are constructed, and the effectiveness positively correlated with the density of thiol groups on their surface. Notably, the nanoodors enable precise brain-targeted delivery, outperforming commercially available oral formulations in terms of drug accumulation in the brain and antidepressant effects. The study of the nanoodor transport and action mechanisms revealed that after binding to ORs, the nanoodors are rapidly delivered to the brain via the olfactory pathway. Nanoodors, the first design to deliver CNS drugs via the olfactory pathway by mimicking natural smells for the treatment of CNS disorders, are expected to achieve clinical transformation, benefiting human health.
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Moying Yang,Yan Yao,Haotian Shen,Fei Teng,Yunuo Liu,Yuyang Ma,Bin Di,Mengxiang Su
Depression has gradually become a serious public health problem. Traditionally, data on depression are mainly derived from questionnaires or antidepressant prescriptions, and these methods may suffer from update delays and survey bias, resulting in a low actual prevalence of depression. To monitor the prevalence of depression in near real-time, this study developed an analytical method of UPLC-MS/MS by wastewater-based epidemiology to detect 10 typical antidepressants and metabolites in four provinces of China. The method has high sensitivity in that the lower limit of quantification was 2 ng/L. And the method provides recoveries and matrix effects ranging from 85.12 % to 102.98 % and 84.95 % to 112.75 %, respectively. The results showed that among the four provinces, the highest average detected concentration of antidepressants was in Jiangsu (91.82 ± 150.46 ng/L), followed by Guangxi (76.06 ± 130.44 ng/L), Anhui (61.53 ± 94.09 ng/L), and Hainan (27.87 ± 28.33 ng/L). Most wastewater treatment facilities had antidepressants such as venlafaxine, fluvoxamine, and agomelatine. The average back-calculated consumption of venlafaxine and fluvoxamine was 815.88 ± 2015.96 mg/day/1000 inh and 497.02 ± 405.21 mg/day/1000 inh, respectively. Based on this study, the estimated prevalence in the population over 15 in Jiangsu, Anhui, and Hainan was finally determined to be 4.90 %, 5.36 %, and 2.93 %, indicating regional diversity. This study offered a workable way to track the prevalence of depression using wastewater-based epidemiology, which aided public health agencies in comprehending the state of depression prevalence.
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INTERNATIONAL JOURNAL OF OBESITY
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2025
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IF 3.8
Zhao Ruolin,Tang Yujie,Zhang Yingbing,Liu Jinwang,Zhong Changsheng,Ji Bozhen,Song Weijia,Zhang Chengtu,Su Jianmin
Background/objective Palmitic acid (PA) is known to be elevated in the follicular fluid of women with obesity, negatively affecting female fertility. However, the mechanism by which PA exposure reduces female fertility is not fully understood, and how it can be treated requires further investigation. Methods We first established in vivo and in vitro models of mouse oocyte maturation at high concentrations of PA and determined the effects of treatment with agomelatine (Ago) which is a melatonin receptor agonist with antioxidant properties. We assessed oocyte maturation rates, spindle morphology and chromosome morphology, oxidative stress and apoptosis levels. Lastly, we examined energy levels, mitochondrial function, and mitochondrial synthesis-related protein expression levels. Results Our results showed that PA exposure disrupted spindle assembly and chromosome alignment, reduced microtubule stability, and impaired the meiotic maturation of oocytes. PA also disrupted mitochondrial function, leading to decreased ATP production, elevated Reactive Oxygen Species(ROS) levels, oxidative stress, and apoptosis. Remarkably, Ago supplementation promoted oocyte quality by restoring spindle/chromosome conformation, maintaining mitochondrial function, lowering ROS levels, and inhibiting apoptosis. Conclusions This study establishes that Ago ameliorates metabolic stress-induced oocyte deterioration through mitochondrial functional restoration, providing mechanistic insights into obesity-associated infertility. Importantly, our study identifies a potentially favorable drug for combating obesity-induced female infertility.
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Antioxidants
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2025
·Vol. 14
·期 4
·410
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IF 6.6
Yan Zhu,Ye Li,Zhaoying Yu,Xiao Chen,Tian Lan,Meijian Wang,Shuyan Yu
Major depressive disorder (MDD) is a common psychiatric disorder characterized by significant mood disturbances and cognitive impairments. Chronic stress, particularly social defeat stress, plays a crucial role in the etiology of depression, with oxidative stress being a pivotal factor in its pathophysiology. Consequently, identifying effective strategies to mitigate oxidative stress and prevent the progression of depression is of paramount importance. Agomelatine, an atypical antidepressant with melatonergic and serotonergic properties, has shown promise in treating MDD due to its unique mechanisms of action. In this study, we aimed to investigate whether agomelatine could ameliorate behavioral deficits in a chronic social defeat stress (CSDS) mouse model. CSDS mice were administered agomelatine (50 mg/kg, intraperitoneally) and exhibited significant reductions in both anxiety-like and depressive-like behaviors in behavioral tests. Further analysis revealed that agomelatine treatment effectively reduced oxidative damage in the hippocampus of CSDS mice. Additionally, agomelatine attenuated mitochondrial dysfunction and restored synaptic plasticity, as evidenced by an increased density of excitatory synapses and enhanced neuronal activity. These findings suggest that agomelatine may exert therapeutic effects by reducing oxidative stress, preserving mitochondrial function, and enhancing synaptic plasticity, providing new insights into its potential as a treatment for chronic social defeat stress-induced depression.
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