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Depression is a global health problem with growing prevalence rates and serious impacts on the daily life of patients. However, the side effects of currently used antidepressants greatly reduce the compliance of patients. Quercetin is a flavonol present in fruits, vegetables, and Traditional Chinese medicine (TCM) that has been proved to have vario...
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... (C5H10O7; Figure 1), a flavonol widely present in nature in the form of glucosides ( Ulusoy and Sanlier, 2020), is one of the main components of different TCM, including Radix Bupleuri, Mulberry leaves, Sophorae Fructus, Inulae Flos, and Crataegi Fructus ( Ding et al., 2021a;Shi et al., 2021;Tu et al., 2022). Many studies have demonstrated that quercetin has a wide range of pharmacological effects such as anti-cancer, antibacterial, anti-oxidation, and memory impairment improvement ( Horowitz and Zunszain, 2015;Suganthy et al., 2016;Babaei et al., 2018a;Kashyap et al., 2019). ...
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... Among these, riboflavin may protect nerves by reducing inflammation and antioxidative stress properties, suggesting its potential as a migraine preventive agent (57). Herbal treatment has the advantages of holistic conditioning, multi-targeting, and long-lasting effects, which are conducive to individualized and fine-tuned treatment for migraine patients (58)(59)(60). In 22 years, Yang et al. (61) showed that in a rat model of nitroglycerin (NTG)-induced migraine, the Chinese herbal formula Xiongshao Zhitongfang (XZR) regulated NO, 5-HT, CGRP, and SP to normal levels, while inhibiting mast cell degranulation and the release of inflammatory factors, which resulted in attenuation of migraine symptoms. ...
Migraine is a prevalent and disabling neurovascular disorder, with women being more susceptible, characterized by unilateral throbbing headache, often accompanied by nausea and vomiting, and often associated with various comorbidities such as brain and cardiovascular diseases, which can have a serious impact on quality of life. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the main first-line medications for the treatment of pain, long-term use often leads to side effects and drug addiction, which emphasizes the need to investigate alternative pain management strategies with fewer adverse effects. Complementary and alternative medicine is a viable pain intervention often used in conjunction with traditional medications, including acupuncture, herbs, moxibustion, transcutaneous electrical stimulation, bio-supplements, and acupressure, which offer non-pharmacological alternatives that are now viable pain management options. This review focuses on the mechanistic doctrine of migraine generation and the role and potential mechanisms of Complementary and Alternative Therapies (CAT) in the treatment of migraine, summarizes the research evidences for CAT as an adjunct or alternative to conventional therapies for migraine, and focuses on the potential of novel migraine therapies (calcitonin gene-related peptide (CGRP) antagonists and pituitary adenylyl cyclase-activating peptide (PACAP) antagonists) with the aim of evaluating CAT therapies as adjunctive or alternative therapies to conventional migraine treatment, thereby providing a broader perspective on migraine management and the design of treatment programs for more effective pain management.
... Among these, riboflavin may protect nerves by reducing inflammation and antioxidative stress properties, suggesting its potential as a migraine preventive agent (57). Herbal treatment has the advantages of holistic conditioning, multi-targeting, and long-lasting effects, which are conducive to individualized and fine-tuned treatment for migraine patients (58)(59)(60). In 22 years, Yang et al. (61) showed that in a rat model of nitroglycerin (NTG)-induced migraine, the Chinese herbal formula Xiongshao Zhitongfang (XZR) regulated NO, 5-HT, CGRP, and SP to normal levels, while inhibiting mast cell degranulation and the release of inflammatory factors, which resulted in attenuation of migraine symptoms. ...
Migraine is a prevalent and disabling neurovascular disorder, with women being more susceptible, characterized by unilateral throbbing headache, often accompanied by nausea and vomiting, and often associated with various comorbidities such as brain and cardiovascular diseases, which can have a serious impact on quality of life. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the main first-line medications for the treatment of pain, long-term use often leads to side effects and drug addiction, which emphasizes the need to investigate alternative pain management strategies with fewer adverse effects. Complementary and alternative medicine is a viable pain intervention often used in conjunction with traditional medications, including acupuncture, herbs, moxibustion, transcutaneous electrical stimulation, bio-supplements, and acupressure, which offer non-pharmacological alternatives that are now viable pain management options. This review focuses on the mechanistic doctrine of migraine generation and the role and potential mechanisms of Complementary and Alternative Therapies (CAT) in the treatment of migraine, summarizes the research evidences for CAT as an adjunct or alternative to conventional therapies for migraine, and focuses on the potential of novel migraine therapies (calcitonin gene-related peptide (CGRP) antagonists and pituitary adenylyl cyclase-activating peptide (PACAP) antagonists) with the aim of evaluating CAT therapies as adjunctive or alternative therapies to conventional migraine treatment, thereby providing a broader perspective on migraine management and the design of treatment programs for more effective pain management.
... Thus, it is often prescribed as a health supplement and used in the production of nutraceuticals. A series of retrospective studies and reviews have demonstrated the efficacy and safety of quercetin [4,5]. Furthermore, clinical observations and experimental studies have also suggested that quercetin can effectively relieve depression and improve neurological health [6,7]. ...
... Based on a network pharmacology analysis of these Chinese medicines, the researchers screened out a total of four antidepressant ingredients, and the list included quercetin. In addition, some researchers have also explored the quercetin-mediated treatment of depression from a pharmacological perspective, demonstrating its effects on neurotransmitter regulation, the increased regeneration of hippocampal neurons, improvements in hypothalamic-pituitary-adrenal functions, as well as reductions in inflammation [4]. Meanwhile, other researchers have applied quercetin clinically to improve emotional states in subjects with cognitive impairment, showing that this compound can maintain redox homeostasis in the brain [6], in line with previous findings [4]. ...
... In addition, some researchers have also explored the quercetin-mediated treatment of depression from a pharmacological perspective, demonstrating its effects on neurotransmitter regulation, the increased regeneration of hippocampal neurons, improvements in hypothalamic-pituitary-adrenal functions, as well as reductions in inflammation [4]. Meanwhile, other researchers have applied quercetin clinically to improve emotional states in subjects with cognitive impairment, showing that this compound can maintain redox homeostasis in the brain [6], in line with previous findings [4]. As demonstrated by Adeoluwa OA et al., quercetin can downregulate pro-inflammatory factors in the hippocampus and microglia, as well as improve behavioral indexes in rats with depressive-like behaviors [37]. ...
Background: Depression is becoming increasingly prevalent around the world, imposing a substantial burden on individuals, families, as well as society. Quercetin is known to be highly effective in treating depression. However, additional research is needed to dissect the mechanisms of its anti-depressive effects. Methods: For this study, Sprague-Dawley (SD) rats were randomized into the control, model, quercetin, or fluoxetine group. The latter three groups were exposed to chronic unpredictable mild stress (CUMS) for 42 d. The first two groups received saline solution daily via oral gavage. Meanwhile, the quercetin group was orally administered a quercetin suspension (52.08 mg/kg) every day, while the fluoxetine group was orally administered a fluoxetine solution (2.08 mg/kg). Here, fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin. The experimental period was 6 weeks. Depressive behaviors in rats were assessed through various physiological and behavioral measures. Additionally, pathological changes in hippocampal tissues were examined using Nissl staining. Serum cytokines were detected using an enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry was employed to quantify the levels and integral optical density (IOD) values of ionized calcium binding adaptor molecule-1 (Iba-1) expression in the brain. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4 (TLR4), and nuclear factor-κappa B P65 (NF-κB P65) in hippocampus. Western blot (WB) technique was employed to observe the protein levels of TLR4, NF-κB P65, and phospho-NF-κB P65 (p-NF-κB P65). Results: After 42 d of exposure to CUMS, rats exhibited a slow increase in body weight, a reduction in food intake, an abnormal preference for sugar water, and aberrant open-field behaviors. Pathological analysis revealed the disintegration, rupture, interruption, and disorganization of hippocampal neuronal cells after CUMS exposure, along with a decrease in Nissl bodies in the CA1 region. This was accompanied by the elevated expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the serum and the upregulation of IL-1β, IL-6, and TNF-α mRNA expression in the hippocampus. Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia. Furthermore, TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues. Quercetin, an antidepressant, could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia, and its therapeutic effect was comparable to fluoxetine. Conclusion: In rat models of CUMS, quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway. These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.
... These findings highlight the potential role of inflammatory processes in the etiology of depression and provide new insights into the development of novel therapeutic strategies for this debilitating condition [45]. Bupleurum contains a variety of flavonoids, which have a good effect on improving neuroinflammation and achieving an antidepressant effect [46][47][48]. ...
The incidence of depression has been steadily rising in recent years, making it one of the most prevalent mental illnesses. As the pursuit of novel antidepressant drugs captivates the pharmaceutical field, the therapeutic efficacy of Traditional Chinese Medicine (TCM) has been widely explored. Chaihu (Bupleurum) has been traditionally used for liver conditions such as hepatitis, liver inflammation, liver fibrosis, and liver cancer. It is believed to have hepatoprotective effects, promoting liver cell regeneration and protecting against liver damage. In addition, Bupleurum has also been used as a Jie Yu (depression-relieving) medicine in China, Japan, Republic of Korea, and other Asian countries for centuries. This review article aims to summarize the research conducted on the antidepressant properties and mechanisms of Bupleurum, as well as discuss the potential of TCM formulas containing Bupleurum. This review highlights various antidepressant ingredients isolated from Bupleurum, including saikosaponin A, saikosaponin D, rutin, puerarin, and quercetin, each with distinct mechanisms of action. Additionally, Chinese herb prescriptions and extracts containing Bupleurum, such as Chaihu Shugansan, Xiaoyaosan, and Sinisan, are also included due to their demonstrated antidepressant effects. This review reveals that these Bupleurum compounds exhibit antidepressant effects through the regulation of neurotransmitter mechanisms (such as 5-HT and DA), the NMDA (N-methyl-D-aspartate) system, brain-derived neurotrophic factor (BDNF), and other intracellular signaling pathways. Collectively, this comprehensive review provides insights into the multiple applications of Bupleurum in the treatment of depression and highlights its potential as an alternative or complementary approach to traditional therapies. However, it is essential to consider the potential adverse effects and clinical restrictions of Bupleurum despite its promising potential. Further research is needed to elucidate its specific mechanisms of action and evaluate its effectiveness in human subjects.
... Research has revealed that quercetin can improve gut microbiota dysbiosis, promote gut microbial balance, restore gut barrier structure and function, and exhibit biological activities such as anti-inflammatory, antioxidant, and antiviral effects (Horowitz and Zunszain, 2015;Suganthy et al., 2016;Babaei et al., 2018;Ulusoy and Sanlier, 2020). It also demonstrates potential pharmacological activities against mental disorders (Chen et al., 2022). Moreover, compared to traditional antidepressants, quercetin has several advantages: 1) Multiple mechanisms of action: Numerous studies have reported that quercetin may exert its antidepressant effects via various mechanisms, such as antioxidation, anti-inflammation, neuroprotection, and modulation of the neurotransmitter system (Sah et al., 2011;Yang et al., 2020;Zhang et al., 2020;Şahin et al., 2020;Ma et al., 2021); 2) Fewer side effects and non-addictive: Quercetin is associated with fewer side effects and lacks the addictive potential of traditional antidepressants, which are often linked to significant side effects (Bschor et al., 2014;Solem et al., 2017). ...
Quercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio and enhanced Cyanobacteria. At the genus level, quercetin downregulated 6 and upregulated 14 bacterial species. Metabolomics analysis revealed that quercetin regulated multiple metabolic pathways, including glycolysis/gluconeogenesis, sphingolipid metabolism, the pentose phosphate pathway, and coenzyme A biosynthesis. This modulation leads to improvements in depression-like phenotypes, anxiety-like phenotypes, and cognitive function, highlighting the therapeutic potential of quercetin in treating depression.
... Multiple studies have suggested the role of quercetin in alleviating anxiety and depression via neuroprotective effects. As a potential antidepressant compound, quercetin is reported to regulate neurotransmitter levels, promote hippocampal neuron regeneration, reduce inflammatory and oxidative stress, and normalize hypothalamus-adrenal axis dysfunction (Chen et al., 2022). Quercetin, the most abundant flavonoid in various fruits violet-colored dotted lines indicate π-sigma interactions. ...
Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis.
Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID. Essential bioactive compounds, potential targets, and signaling pathways were predicted using in silico analysis, including BA-TAR, PPI, BA-TAR-PATH network construction, and GO and KEGG pathway enrichment analysis. Later on, with molecular docking analysis, the interaction of essential bioactive compounds of A. laxiflora and predicted core targets of depression were verified.
Results: The network pharmacology approach identified 15 active compounds, a total of 219 compound-related targets, and 14,574 depression-related targets with 200 intersecting targets between them. SRC, EGFR, PIK3R1, AKT1, and MAPK1 were the core targets, whereas 3-acetyloleanolic acid and 3-acetylursolic acid were the most active compounds of A. laxiflora with anti-depressant potential. GO functional enrichment analysis revealed 129 GO terms, including 82 biological processes, 14 cellular components, and 34 molecular function terms. KEGG pathway enrichment analysis yielded significantly enriched 108 signaling pathways. Out of them, PI3K-Akt and MAPK signaling pathways might have a key role in treating depression. Molecular docking analysis results exhibited that core targets of depression, such as SRC, EGFR, PIK3R1, AKT1, and MAPK1, bind stably with the analyzed bioactive compounds of A. laxiflora.
Conclusion: The present study elucidates the bioactive compounds, potential targets, and pertinent mechanism of action of A. laxiflora in treating depression. A. laxiflora might exert an antidepressant effect by regulating PI3K-Akt and MAPK signaling pathways. However, further investigations are required to validate.
... Currently, the most extensively studied quercetin derivatives are glyc sides and methyl derivatives ( Figure 1). While the former enhances water solubility an thus facilitates the absorption and utilization of quercetin in humans by attaching sug groups [31], the latter improves the stability, bioavailability, and overall drug properti of quercetin through methylation [32]. Therefore, in the following, we mainly discuss th therapeutic effects of quercetin and its glycosides and methyl derivatives during sepsis ...
... Currently, the most extensively studied quercetin derivatives are glycosides and methyl derivatives (Figure 1). While the former enhances water solubility and thus facilitates the absorption and utilization of quercetin in humans by attaching sugar groups [31], the latter improves the stability, bioavailability, and overall drug properties of quercetin through methylation [32]. Therefore, in the following, we mainly discuss the therapeutic effects of quercetin and its glycosides and methyl derivatives during sepsis. ...
Sepsis is a syndrome of organ dysfunction caused by an uncontrolled inflammatory response, which can seriously endanger life. Currently, there is still a shortage of specific therapeutic drugs. Quercetin and its natural derivatives have received a lot of attention recently for their potential in treating sepsis. Here, we provide a comprehensive summary of the recent research progress on quercetin and its derivatives, with a focus on their specific mechanisms of antioxidation and anti-inflammation. To obtain the necessary information, we conducted a search in the PubMed, Web of Science, EBSCO, and Cochrane library databases using the keywords sepsis, anti-inflammatory, antioxidant, anti-infection, quercetin, and its natural derivatives to identify relevant research from 6315 articles published in the last five years. At present, quercetin and its 11 derivatives have been intensively studied. They primarily exert their antioxidation and anti-inflammation effects through the PI3K/AKT/NF-κB, Nrf2/ARE, and MAPK pathways. The feasibility of these compounds in experimental models and clinical application were also discussed. In conclusion, quercetin and its natural derivatives have good application potential in the treatment of sepsis.
... Traditional Chinese medicine (TCM) profits from the flexible utilization of the concepts of holistic view and diagnosis and treatment in clinical, plays a role in the treatment of multiple diseases, especially in the fight against COVID-19, which has shown the world the great potential of TCM (Lyu et al., 2021;Chen et al., 2022). In recent years, the antidepressant effects of herbal formulas and individual components have been gradually confirmed He et al., 2022). ...
Depression, a global health problem with growing prevalence, brings serious impacts on the daily life of patients. However, the antidepressants currently used in clinical are not perfectly effective, which greatly reduces the compliance of patients. Berberine is a natural quaternary alkaloid which has been shown to have a variety of pharmacological effects, such as hypoglycemic, lipid-regulation, anti-cancer, antibacterial, anti-oxidation, anti-inflammatory, and antidepressant. This review summarizes the evidence of pharmacological applications of berberine in treating depression and elucidates the mechanisms of berberine regulating neurotransmitter levels, promoting the regeneration of hippocampal neurons, improving hypothalamic-pituitary-adrenal axis dysfunction, anti-oxidative stress, and suppressing inflammatory status in order to provide a reference for further research and clinical application of berberine.
... However, the regulatory mechanisms by which the two exert therapeutic effects are different. Quercetin cloud also protect against liver damage by regulating related inflammatory factors [27]. Furthermore, paeoniflorin and alibiflorin in Paeonia lactiflora have been proven to have the effect of improving depressive behavior [28][29][30]. ...
... In a recent study, QUR-3-O-glucuronide at 150 and 300 mg/kg oral doses exerted significant sedative effects in TS-induced mice [75]. Moreover, a recent review found that QUR and some of its derivatives within the range of 10 to 2000 mg/kg (oral) have significant anti-depressant effects in experimental animals (e.g., mice, rats, and zebrafish) [76]. QUR has a claimed half-life of 11 to 28 h, and human individuals can absorb considerable quantities of the substance via meals or supplements [77]. ...
Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study's putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABAA) subunits. Results revealed that QUR and LIN cause dose-dependent anti-depressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has be er binding interaction with GABAA α3, β1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABAA receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway.
