Depression, or major depressive disorder, is a prevalent psychological disorder, but its underlying mechanisms remain understood, hindering effective prevention and treatment. This study investigated the protective effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and explored the underlying mechanisms using in vivo and in vitro experiments. Metabonomic analysis revealed that CUMS significantly elevated serum levels of argininosuccinic acid (ASA), which were strongly correlated with depression-like behaviors in rats, suggesting a potential role of ASA in depression pathogenesis. Intracerebral injection of ASA induced depression-like behaviors and upregulated inflammatory markers (inhibitory-κB kinase alpha [IKK-α], nuclear factor kappa b subunit p65, nod-like receptor protein 3 [NLRP3]) and pyroptosis-related proteins ( cysteine-aspartic acid protease-1 [caspase-1], Gasdermin D) in the rats' hippocampus (HPC). Quercetin treatment ameliorated CUMS-induced depressive behaviors, reduced serum ASA levels, and inhibited hippocampal inflammation and pyroptosis. In subsequent in vitro experiments with primary astrocytes isolated from the HPC of neonatal rats aged 1-3 days, reactive oxygen species, NLRP3, and caspase-1 inhibitors were used to demonstrate that quercetin, through its antioxidant and anti-inflammatory effects, could attenuate ASA-induced activation of the nuclear factor- kappa B/NLRP3 inflammatory pathway and subsequent pyroptosis, thereby protecting astrocytes. Collectively, this study suggested that ASA could induce NLRP3/caspase-1 activation via reactive oxygen species, triggering astrocyte pyroptosis and contributing to depression. Notably, quercetin can effectively alleviate stress-induced depression-like behaviors by inhibiting ASA-induced astrocyte pyroptosis and subsequent astrocyte loss in the HPC. This study provides valuable insights into the potential of quercetin as a therapeutic agent targeting cellular mechanisms in depression, offering new perspectives for treating this disorder.

Depression is a serious mental disease, and its accompanying abnormal changes in peripheral organs, including the kidney, are easy to be ignored. The metabolic abnormalities of the kidney and other organs will inevitably affect the progress of depression through the circulatory system. Quercetin has attracted much attention as a flavonoid with anti-inflammatory, antioxidant, neuroprotective, and antidepressant potential. Chronic unpredictable mild stress (CUMS) model is a reliable and effective animal model of depression. We hypothesize that quercetin has the potential to alleviate the abnormalities in renal metabolic profile induced by CUMS. An ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) platform was used to analyze renal metabolites, and the obtained data were analyzed using the Progenesis QI software for peak alignment, peak picking, and data normalization. Based on the data processing method with fold change > 2 or < 0.5, the false discovery rate corrected was p < 0.05, and a variable importance in projection score was > 1; a total of 16 differential metabolites were identified, including L-histidine, D-glucose 1-phosphate, cytidine, D-Ribulose 5-phosphate, D-xylulose 5-phosphate, uridine monophosphate (UMP), uracil, glucuronide, prostaglandin-F2α (PGF2ɑ), arachidonic acid, 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-epoxyeicosatrienoic acid (14,15-EET), deoxycytidine, anserine, carnosine, and PC (14:0). Among them, the intensities of anserine, carnosine, L-histidine, and 14,15-EET were significantly reduced (p < 0.01), while the intensities of other metabolites were significantly increased in the CUMS group compared with the control group (p < 0.01). When CUMS model rats received high-dose quercetin treatment, the intensities of above differential metabolites were significantly restored (p < 0.05 or p < 0.01). Further, pathway enrichment analysis revealed abnormalities in arachidonic acid (AA) metabolism, pyrimidine metabolism, amino acid metabolism, and pentose and glucuronide acid interconversion in the kidney. The renal histopathological examination revealed CUMS induced renal tubular epithelial cell shedding and glomerular atrophy. High-dose quercetin can improve renal metabolic disorders and renal pathological changes caused by CUMS. Mechanistically, quercetin improves renal metabolic disorders by enhancing the antioxidant capacity and inhibiting the secretion of inflammatory factors. Moreover, quercetin can regulate renal AA metabolism disorder by inhibiting soluble epoxide hydrolase activity. High-dose quercetin (50 mg/kg bw) has a certain protective effect on kidney damage induced by CUMS, providing new strategies for quercetin to prevent depression.

Perimenopausal depression is a subtype of depression that seriously harms women's health. The pathogenesis of perimenopausal depression remains unclear, which limits its prevention and therapy. Quercetin is a flavonoid with antidepressant and estrogen-like effects. This study aimed to explore the effects of quercetin on spleen metabolism in rats with perimenopausal depression and its potential mechanism. Untargeted metabolomics was employed to obtain splenic metabolite profiles, and 21 differential metabolites were identified. Pathway analysis revealed that glycerophospholipid metabolism, retinol metabolism, steroid hormone biosynthesis, and linoleic acid metabolism were disturbed. Notably, Spearman's rank correlation analysis revealed that differential metabolites were significantly correlated with behavioral test results (p < 0.01). After treatment with quercetin, the intensities of the above differential metabolites were restored (p < 0.01), indicating that quercetin can improve the spleen metabolic disorder induced by the perimenopausal depression model. Further study showed that quercetin can increase the expression of PPAR-alpha in the hippocampus and spleen, reduce the expression of NF-kappa B and the levels of TNF-alpha and IL-6 in the spleen, and restore the expression of CREB and BDNF in the hippocampus (p < 0.05 or p < 0.01). Our study is the first to explore the effect of quercetin on spleen metabolism disorders in perimenopausal depression model rats using untargeted metabolomics. Quercetin can improve spleen metabolism disorders through multiple pathways, which may be related to the restoration of hippocampal neuroplasticity and reduction of spleen inflammation by regulating the brain-spleen axis. Our study provides a potential strategy for preventing and treating perimenopausal depression.

BACKGROUND:Perimenopausal depression seriously harms women's physical and mental health, and there is currently no safe and effective prevention and treatment method. Flavonoids not only have antidepressant effects, but can also promote the synthesis and utilization of high-density lipoprotein cholesterol (HDL-c), which are closely associated with depression. This study aimed to explore the association between flavonoid intake and the risk of perimenopausal depression and the mediating role of HDL-c. METHODS:The data of this study were collected from the US National Health and Nutrition Examination Survey (NHANES) continuously from 2005 to 2018, and flavonoid intakes data were extracted from the Food and Nutrient Database for Dietary Studies. Multivariate logistic regression was used to estimate the association between flavonoid intake and the risk of perimenopausal depression, and the mediating effect model was constructed to explore the impact of HDL-c on the correlation. RESULTS:Total 4603 perimenopausal female participants were included in this study, results showed that flavonoid intake was inversely associated with the risk of perimenopausal depression, and positively associated with serum HDL-c levels. These associations persisted after adjustment for relevant covariates. Serum HDL-c mediated the association between flavonoid intake and the risk of perimenopausal depression. LIMITATIONS:As a cross-sectional study, which cannot determine the causal relationship between flavonoid intake and perimenopausal depression. CONCLUSION:Our research showed that flavonoid intake, perimenopausal depression, and serum HDL-c are pairwise correlated, revealing that higher flavonoid intake was associated with a lower risk of perimenopausal depression, which may be mediated in part by serum HDL-c.

Perimenopausal depression is a subtype of depression whose pathogenesis remains unclear. Prefrontal cortex (PFC) is an advanced center for cognitive and emotional integration, which plays a critical role in the development of perimenopausal depression. This study aimed to explore the impact of quercetin on metabolic disorders in the PFC of perimenopausal depression rat models and its potential role in inhibiting ferroptosis using untargeted metabolomics technology. Female Wistar rats were randomly divided into four groups: sham group (C), model group (D), model + 17β-estradiol (E2) group (E: 0.27 mg/kg.bw), and model + quercetin group (Q: 50 mg/kg.bw). The perimenopausal depression rat model was established by ovariectomy combined with chronic unpredictable mild stress. After the experiment, the PFC was collected for metabolomic analysis and related index detection. A total of 13 differential metabolites were identified in the model group. Spearman's rank correlation analysis revealed a significant correlation between differential metabolites and behavioral outcomes (p < 0.01). Pathway enrichment analysis of differential metabolites indicated that the metabolic disorders in the PFC of the model group primarily involved lipid metabolism, amino acid metabolism, and carnitine synthesis, which were related to ferroptosis, characterized by the generation of lipid peroxides and the imbalance between oxidation and antioxidation systems. It is worth noting that quercetin can regulate metabolic disorders and inhibit ferroptosis in the PFC of rat models with perimenopausal depression by exerting anti-inflammatory, neuroprotective, and antioxidant effects, providing a new strategy for quercetin in the prevention and treatment of perimenopausal depression.

Diabetic retinopathy (DR) is one of the major complications of diabetes, resulting in severe vision loss. Traction retinal detachment (TRD) is the main factor affecting the effect of proliferative diabetic retinopathy (PDR) surgery. Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the proteomes of the vitreous in the TRD, vitreous hemorrhage (VH) and macular hole (MH) groups. By employing bioinformatics tools for GO and KEGG pathway annotation, as well as conducting protein-protein interaction(PPI) network analysis, we investigated the functional enrichment of proteins in the TRD vitreous and their associated pathways. Additionally, peptide center analysis was performed on the proteomic data to identify key differentially expressed proteins based on screening results. Bioinformatics analysis showed that DEPs is mainly enriched in the complement, the coagulation cascade systems and regulation of actin cytoskeleton. The protein interaction network analysis showed that the central proteins were mainly related to sphingolipid metabolism. APOA4, CHI3L1, LTBP2 were significantly up-regulated in TRD, which were related to the complement system, coagulation cascade and platelet activation, sphingolipid metabolism and other pathways. APOA4 and CHI3L1 protein in patients with TRD group raised significantly in the vitreous humor, shows the potential biomarkers for TRD.

Depression is a mental disorder, and the complexity of its pathogenesis affects the treatment and prevention of depression. Flavonoids possess a variety of biological effects, including antidepressant properties. Quercetin, a natural flavonoid, exhibits antioxidant, antidepressant and anti-inflammatory effects. This research investigated the antidepressant properties of quercetin on rats induced by chronic unpredictable mild stress through untargeted metabolomics. A total of 96 rats were randomly allocated across six groups: control group, quercetin-treated groups receiving distinct dosages (10 and 50 mg/kg bw, respectively), depression model group, and different dosages of quercetin intervention in the depression model. During the 8 wk chronic unpredictable mild stress modeling process, quercetin was administered to the rats via gavage once daily. After 8 wk modeling, rat urine samples and prefrontal cortex were collected for untargeted metabolomics research and related detection, respectively. 19 differential metabolites were identified in the urine of chronic unpredictable mild stress-induced rats, and pathway analysis indicated metabolic disorders in rats, including arachidonic acid metabolism and amino acid metabolism. This study found that the elevation of urinary PGE2 and LTB4 is closely associated with the activation of the NF-κB/NLRP3 pathway in the PFC of chronic unpredictable mild stress-induced rats. Metabolomics reveals that quercetin can ameliorate metabolic disorders induced by chronic unpredictable mild stress through multiple pathways, and inhibit the activation of the NF-κB/NLRP3 pathway in the PFC by exerting anti-inflammatory and antioxidant effects. This study offers novel insights into the role of quercetin for the prevention and management of depression.

Perimenopausal depression is a psychiatric disorder that occurs around the time of menopause and seriously affects women's health. The pathogenesis of perimenopausal depression is unclear which affects its prevention and treatment. Quercetin is a flavonoid compound with antidepressant and estrogen-like effects. The aim of this research was to investigate the role of quercetin on adrenal gland metabolic disorders in perimenopausal depressed rats based on untargeted metabolomics. Female Wistar rats with no difference in sucrose preference were randomly separated into four groups (n = 12): sham-operated group; perimenopausal depression model group; model + 50 mg/kg.bw quercetin group; model + 0.27 mg/kg.bw 17 beta-estradiol group. After successful modeling, adrenal gland and hypothalamic samples were collected for metabolomics experiments and detection of related indicators. A total of 22 differential metabolites were identified in the model group, and pathway analysis revealed adrenal gland metabolism abnormalities including steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism. Notably, Spearman's rank correlation analysis between differential metabolites and rat behavioral results showed strong positive or negative correlations (P < 0.01). Meanwhile, the hypothalamus of the model group showed TrkB-BDNF signaling pathway abnormality, and the HPA axis was found to play an important role in perimenopausal depression. Treatment with quercetin or 17 beta-estradiol restored these abnormal changes. It suggested that quercetin can regulate adrenal metabolic disorders through multiple pathways, thereby ameliorating perimenopausal depression.Further more, quercetin can modulate HPA axis through the TrkB-BDNF signaling pathway. This research provides new ideas for the application of quercetin in the precaution and treatment of perimenopausal depression.

Perimenopausal depression is often accompanied by metabolic disorders, which have long-term harmful effects on women’s physical and mental health. Quercetin, a kind of phytoestrogen, has anti-inflammatory, antioxidant, and nerve-protective effects, and can regulate various metabolic disorders. This study aims to investigate the effect of quercetin on hippocampal metabolic disorder in perimenopausal depression rat models based on untargeted metabolomics technology. The rat model of perimenopausal depression was established by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Rats with no difference in sucrose preference were randomly divided into four groups (n = 12): sham group, OVX-CUMS group (model group), model plus quercetin group, and model plus 17β-estradiol group. At the end of the experiment, hippocampal tissues were collected for untargeted metabolomics analysis, morphological analysis, and detection of related indicators. Metabolomics identified 23 differential metabolites in the model group, and the pathway analysis discovered hippocampus metabolic abnormalities including the metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, and ubiquinone biosynthesis, accompanied by an increase in oxidative stress, inflammation, and lipid peroxidation indicators. At the same time, the morphological characteristics of ferroptosis occurred in the hippocampus in the model group. These abnormal changes were reversed by treatment with quercetin or 17β-estradiol. Quercetin can improve perimenopausal depression by regulating hippocampal metabolic disorders and reducing hippocampal ferroptosis in rats. These findings provide a new strategy for the use of quercetin in the prevention and treatment of perimenopausal depression.

Perimenopausal depression is a subtype of depression and is prevalent among perimenopausal women, which has brought a heavy burden to family and society. The pathogenesis of perimenopausal depression is still unclear, which affects the prevention and treatment of perimenopausal depression to a certain extent. Quercetin is a flavonoid compound, and has estrogenic activity and pharmacological effects such as antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated whether quercetin improved perimenopausal depression-like behaviors and potential mechanism. The results demonstrated that quercetin could alleviate the depression-like behaviors in perimenopausal depression rat model, inhibit astrocyte activation, improve ferroptosis-associated mitochondrial damage (such as mitochondrial pyknosis and mitochondrial cristae reduction) in hypothalamus, increase the expressions of histone 3 lysine 9 acetylation (acetyl-H3K9), ferroptosis-associated protein including glutathione peroxidase 4 (GPX4) and Xc- antiporter (SLC7A11), and reduce the expressions of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1 (IRE1α), phosphorylated IRE1α (p-IRE1α), X-box binding protein 1 (XBP1) and glucose-regulated protein 78 (GRP78) in hypothalamus of perimenopausal depression rat model. Furtherly, in vitro study indicated that quercetin could restore histone acetylase (HAT)/histone deacetylase (HDAC) homeostasis through binding to estrogen receptors and increase the expression of acetyl-H3K9, inhibiting ferroptosis through IRE1α/XBP1 pathway in astrocytes of hypothalamus. Our findings demonstrated that acetyl-H3K9 is a crucial target in development of perimenopausal depression, and quercetin exhibited antidepressant effects through modulating acetyl-H3K9 mediated ferroptosis in perimenopausal depression. Quercetin might be the prevention and adjuvant treatment strategy of perimenopausal depression.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder emerging during early childhood. However, the mechanism underlying the pathogenesis of ASD remains unclear. This study investigated the alterations of elements in serum and prefrontal cortex of BTBR T + tf/J (BTBR) mice and potential mechanisms. The male BTBR mice were used for experimental group and C57BL/6 J (C57) mice were used for control group (n = 15). After behavioral tests were monitored, serum and prefrontal cortex of mice were analyzed by ICP-MS. The results demonstrated that the level of copper (Cu) was increased, and the levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co), iron (Fe) and zinc (Zn) were decreased in BTBR mice compared to C57 mice (p < 0.01). The levels of above differential elements in serum demonstrated positive correlations with those in prefrontal cortex. Meanwhile, differential elements in prefrontal cortex had correlations with the total distance traveled (open field test) and the number of marbles buried (marble burying test) in BTBR mice (p < 0.05 or p < 0.01). The abnormally changed elements in serum might cross blood–brain-barrier into the brain and lead to oxidative stress, causing inflammation. Furtherly, the levels of inflammation-related indicators including tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were increased in prefrontal cortex of BTBR mice (p < 0.01), which were consistent with the aforementioned results. Our study suggested that the abnormal elements in the serum of BTBR mice may cause oxidative stress and inflammation in prefrontal cortex, which might contribute to increase the understanding of ASD pathogenesis.

This study investigated the effects of quercetin on the alterations of serum elements in perimenopausal depression rat model induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS) and possible mechanisms. According to the results of the sucrose preference test, the rats were randomly assigned to four groups: sham, OVX-CUMS, OVX-CUMS + 17β-estradiol (17β-estradiol: 0.27 mg/kg.bw), and OVX-CUMS + Quercetin (Quercetin: 50 mg/kg.bw). At the end of experiment, serum and prefrontal cortex of rats were collected. The inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co) and zinc (Zn) decreased, and levels of iron (Fe) and copper (Cu) increased in serum and prefrontal cortex of OVX-CUMS rats compared with sham group ( p < 0.01). Meanwhile, the levels of the above elements in prefrontal cortex had correlation with behavioral characteristics in OVX-CUMS rats ( p < 0.05 or p < 0.01). The abnormal elements in serum may cross blood–brain-barrier into the brain and induce oxidative stress, leading to ferroptosis. Furtherly, the expressions of ferroptosis-related protein including GPX4 and SLC7A11 were decreased in prefrontal cortex of OVX-CUMS rats ( p < 0.01), which confirmed the above results. Quercetin treatment restored the above abnormal indicators ( p < 0.05 or p < 0.01) induced by OVX-CUMS in rats. Our study suggested that quercetin regulated variation of elements in serum and prefrontal cortex, further inhibiting ferroptosis in prefrontal cortex through alleviating oxidative stress in OVX-CUMS rats.

Depression is the most prevalent psychiatric disease, and its pathogenesis is still unclear. Currently, studies on the pathogenesis of depression are mainly focused on the brain. The liver can modulate brain function via the liver-brain axis, indicating that the liver plays an important role in the development of depression. This study aims to explore the protective effect of quercetin against chronic unpredictable mild stress (CUMS)-induced metabolic changes and the corresponding mechanisms in the rat liver based on untargeted metabolomics technology. In this study, 96 male rats were divided into six groups: control, different doses of quercetin (10 mg per kg bw or 50 mg per kg bw), CUMS, and CUMS + different doses of quercetin. After 8 weeks of CUMS modeling, the liver samples were collected for metabolomics analysis. A total of 17 altered metabolites were identified, including D-glutamic acid, S-adenosylmethionine, lithocholylglycine, L-homocystine, prostaglandin PGE2, leukotriene E4, cholic acid, 5-methyltetrahydrofolic acid, taurochenodeoxycholic acid, S-adenosylhomocysteine, deoxycholic acid, folic acid, L-methionine, leukotriene C5, estriol-17-glucuronide, PE, and PC, indicating that methionine metabolism, bile acid metabolism, and phosphatidylcholine biosynthesis are the major pathways involved in CUMS-induced hepatic metabolic disorders. Hepatic methylation damage may play a role in the pathophysiology of depression, as evidenced by the first discovery of the abnormality of hepatic methionine metabolism. Abnormal changes in hepatic bile acids may provide stronger evidence for depression pathogenesis involving the microbiota-gut-brain axis, suggesting that the liver is involved in depression development and may be a treatment target. The quercetin treatment alleviated the CUMS-induced liver metabolism disorder, suggesting that quercetin may protect against depression by regulating liver metabolism.

Natural flavonoids are the most plentiful form of polyphenols. Given the anti-inflammatory and antioxidant properties of flavonoids, researchers discovered that it might be effective in treating depression and anxiety. The effect of flavonoids on depression and anxiety was investigated by a meta-analysis and systematic review. We searched PubMed, Embase, and Medline databases up to October 15, 2021. We selected 11 studies, among them, 10 studies were chosen to evaluate the depression effects of flavonoids and 7 studies were used to assess anxiety disorder. The meta-analysis showed that flavonoids have an overall significant effect on depression (p = 0.004, Hedge's g = -0.487, 95% CI -0.814 to -0.160) and anxiety (p = 0.006, Hedge's g = -0.741, 95% CI -1.266 to -0.217). Subgroup analysis indicated that the symptoms of depression were significantly improved in the studies when the dose of flavonoids was 50-100mg/day or the treatment duration was >= 8weeks. Anxiety symptoms were improved in the studies with the dose of flavonoids was >= 50mg/day. There was no evidence of publication bias. Our findings suggest that flavonoids might improve symptoms of depression and anxiety. However, a small number of participants and studies were included in this meta-analysis. Therefore, the results should be interpreted with caution.

This research aimed to explore the protective effect of quercetin against nephrotoxicity induced by four organophosphate pesticide mixtures (PM) using untargeted metabolomics technology in rat kidneys. Sixty male Wistar rats were randomly divided into six groups: control, low-dose quercetin treated (10 mg/kg bw), high-dose quercetin treated (50 mg/kg bw), PM-treated, and two dosages of quercetin + PM-treated. Metabolomics results showed that 17 differential metabolites were identified in the PM-treated group, and pathway analysis revealed that renal metabolic disorders include purine metabolism, glycerophospholipid metabolism, and vitamin B6 metabolism. When high-dose quercetin and PM-treated were administered to rats concurrently, the intensities of differential metabolites were substantially restored (p < 0.01), suggesting that quercetin can improve renal metabolic disorders caused by organophosphate pesticides (OPs). Mechanistically, quercetin could regulate the purine metabolism disorder and endoplasmic reticulum stress (ERS)-mediated autophagy induced by OPs by inhibiting XOD activity. Moreover, quercetin inhibits PLA2 activity to regulate glycerophospholipid metabolism and it could also exert antioxidant and anti-inflammatory effects to correct vitamin B6 metabolism in rat kidneys. Taken together, the high dose of quercetin (50 mg/kg. bw) has a certain protective effect on OPs-induced nephrotoxicity in rats, which provides a theoretical basis for quercetin against nephrotoxicity caused by OPs.

Cadmium (Cd) is known to cause damage to the liver. In this study, metabolomics technology was used to investigate the effect of quercetin (QE) on Cd-induced hepatotoxicity. A total of 60 male SD rats were randomly divided into the following six groups: control group (C), low and high-dose QE group (Q1: 10 mg/kg·bw, Q2: 50 mg/kg·bw), Cd group (D), low and high-dose QE and Cd combined intervention group (DQ1, DQ2). The rats were given Cd chloride (CdCl2) at a concentration of 40 mg/L through free drinking water. After 12 weeks of treatment, liver samples of rats were collected for metabonlomic analysis. A total of 12 metabolites were identified, the intensities of PC (18:0/14:1(9Z)) and arachidonate acid were decreased in the Cd-treated group (p < 0.01), whereas the intensities of chenodeoxyglycocholic acid, cholic acid, taurochenodesoxycholic acid, glycocholic acid, prostaglandin D2, 15-deoxy-d-12,14-PGJ2, oxidized glutathione, cholesterol, protoporphyrin IX, bilirubin were increased significantly in the Cd-treated group compared with group C (p < 0.01). When rats were given high doses of QE and Cd at the same time, the intensity of the above metabolites was significantly restored in group DQ2. Results suggest that the protective effect of QE on Cd-induced liver injury is associated with antioxidant activity of QE, as well as QE can regulates hepatic bile acid metabolism by affecting FXR and BSEP, and regulates AA metabolism by inhibiting Cd-induced activities of COX-2 and PLA2.

Depression is a common and serious psychiatric disorder, but current conventional antidepressants have limited efficacy and significant side effects. Thus, better antidepressants are urgently needed. This study aimed to investigate the antidepressant-like effects and potential mechanism of quercetin by evaluating the changes of serum elements in chronic unpredictable mild stress (CUMS) rats. Based on the results of the sucrose preference test (SPT), 96 rats were randomly assigned to six groups: control, different dosages of quercetin (10 and 50 mg/kg·bw, respectively), depressed, and different dosages quercetin plus depressed groups. After 8 weeks of CUMS modeling, rat serum was collected. Fifteen elements in serum were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and related enzyme indicators, antioxidant indicators, and inflammatory cytokines were detected to further explore the potential mechanism. Besides, the accuracy and precision of the method were evaluated. The results showed that the levels of iron (Fe), copper (Cu), and calcium (Ca) in serum significantly increased (p ≤ 0.001), while the levels of magnesium (Mg), zinc (Zn), selenium (Se), and cobalt (Co) significantly decreased (p ≤ 0.001) in depressed group compared with the control group. The levels of the remaining eight elements did not change significantly. When high-dose quercetin was administered to depressed rats, the levels of the above seven elements significantly restored (p ≤ 0.001). This study suggests that quercetin (50 mg/kg·bw) has a regulatory effect on serum elements in CUMS rats, which may be mediated by reducing oxidative stress, inhibiting inflammation, and regulating a variety of neurotransmitter systems.

Acrylamide (AA) widely exists in the human diet, which makes the public inevitably exposed to AA in daily life. This study aimed to investigate the effects of quercetin on AA-induced hepatotoxicity utilizing metabolomics technology. Sixty male Wistar Rats were randomly divided into six groups: control, two dosages of quercetin intervention [10 and 50 mg/kg body weight (bw)], AA-treated [5 mg/kg bw], and two dosages of quercetin combined with AA intervention. AA and quercetin were given to rats via drinking water and gavage respectively. After 16 weeks of treatment, liver samples were collected for metabolomics analysis. 16 metabolites were finally identified, the intensities of glutathione and NADP were decreased (p < 0.01), whereas the intensities of taurodeoxycholic acid, glycocholic acid, cholic acid, sphingosine, sphingosine1-phosphate, stearidonyl carnitine, N-undecanoylglycine, cholesterol, 13,14-Dihydro-15-keto-PGE2, LysoPE (20:5), LysoPE (18:3), LysoPC (20:4), and PC (22:5) were increased (p < 0.01) in the AA-treated group than those in the control group. After high-dose quercetin (50 mg/kg bw) plus AA treated concurrently to rats, the contents of the above 16 metabolites were significantly restored. This research showed that 50 mg/kg quercetin can alleviate AA-induced hepatotoxicity by reducing oxidative stress and inflammatory injury and regulating lipid metabolism.

The current study aimed to investigate the hepatotoxicity of rats administered with chronic low-dose acrylamide (AA) by using metabonomics technology on the basis of ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). A total of 40 male Wistar rats were randomly divided into the following four groups: control, low-dose AA (0.2 mg/kg bw, non-carcinogenic end-point based on the induction of morphological nerve changes in rats), middle-dose AA (1 mg/kg bw), and high-dose AA (5 mg/kg bw). The rats continuously received AA by administering it in drinking water daily for 16 weeks. After the treatment, rat livers were collected for metabonomics analysis and histopathology examination. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used to investigate the metabonomics profile changes in rat liver tissues and screen the potential biomarkers. Fourteen metabolites were identified with significant changes in intensities (increased or decreased compared with the control group) as a result of treatment (p < 0.05 or p < 0.01). These metabolites included tauro-b-muricholic acid, docosapentaenoic acid, sphingosine 1-phosphate, taurodeoxycholic acid, lysoPE(20:5), cervonyl carnitine, linoleyl carnitine, docosahexaenoic acid, lysoPC(20:4), lysoPE(18:3), PA(20:4), stearidonyl carnitine, alpha-linolenic acid, and lysoPA(18:0). Results showed that chronic exposure to AA at NOAEL (0.2 mg/kg bw) exhibited no toxic effect in rat livers at the metabolic level. AA induced oxidative stress to the liver and disrupted lipid metabolism. The results of liver histopathology examination further supported the metabonomic results.