Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade

Gao, Wenqi; Wang, Wei; Yan, Peng; Deng, Zhifang

doi:10.1007/s11011-019-0389-5

Cited by 86 publications

(42 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is speculated that C3a binding to C3aR may activate and phosphorylate AKT, which is associated with the activation of WNT/β-catenin signaling pathway. Similarly, IL-1β binds to and activates the IL-1R, which recruits MyD88, IRAK, TRAF6 and TAK1 to its intracellular domains leading to the activation and phosphorylation of AKT (27,29,53). The phosphorylated AKT interacts with β-catenin/Tcf4, which affects the expression of a multitude of downstream genes.…”

Section: Discussionmentioning

confidence: 99%

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Huang

Zhang

Lin³

et al. 2019

Brain Pathology

View full text Add to dashboard Cite

Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/β-catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/ kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2 + oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28-day septic rats. The number of PLP + and MBP + cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g-ratios were higher. This was coupled with an increase in number of NG2 + cells and decreased number of CC1 + cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above-mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/β-catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/β-catenin signaling pathway, which would contribute ultimately to axonal hypomyelination. Huang et al C3a induces hypomyelination in the septic brain

show abstract

Section: Discussionmentioning

confidence: 99%

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Huang

Zhang

Lin³

et al. 2019

Brain Pathology

View full text Add to dashboard Cite

show abstract

“…As the most common avonoid, kaempferol has attracted much attention due to its anti-cancer, anti-in ammatory, antioxidant, antibacterial and antiviral effects. Gao et al have com rmed that antidepressive effects of kaempferol are mediated by reduction of oxidative stress, proin ammatory cytokines and up-regulation of AKT/β-catenin cascade [19]. Stigmasterol has been found to exert neuro-protective effect through reduction of oxidative stress and inactivation of autophagy via AMPK/mTOR and JNK pathways [20].…”

Section: Discussionmentioning

confidence: 99%

“…The novel coronavirus disease 2019 (COVID- 19), caused by the severe acute respiratory syndrome coronavirus-2, is in the midst of worldwide panic and global health concern since December 2019 [1]. The most common symptoms of COVID-19 illness are fever, cough, and dyspnea [2].…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology-based active compounds and pharmacological mechanisms of ginseng for depression in post-COVID-19

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Introduction: The novel coronavirus disease 2019 (COVID-19) is in the midst of worldwide panic. Sudden onset of an immediate life-threatening illness, quarantine and unemployment caused by epidemic are all contributors to depression. Ginseng has been reported to be an effective and safe clinical treatment on both immune-regulation and anti-depression. However, the mechanism of its anti-depression effect has not been fully characterized. In order to provide theoretical guidance for further clinical application in post-pandemic, we investigated active compounds and pharmacological mechanisms of ginseng to exert anti-depressant activity using network pharmacology, and discussed the active ingredients with immune-regulation and anti-depression.Methods: Information on compounds in ginseng was obtained from public databases, and genes related to depression were gathered using the GeneCards database. Networks of ginseng-associated targets and depression-related genes were constructed through STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of ginseng for depression were identified using Cytoscape and Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: Network pharmacological analysis of ginseng in treatment of depression identified 16 active ingredients, 47 potential targets, 32 GO terms, and 8 target gene-regulated major pathways. Among them, kaempferol, beta-sitosterol, stigmasterol, fumarine and frutinone A are bioactive compounds and key chemicals. Core genes in PPI network were AKT1, CASP3, NOS3, TNF, and PPARG. Enrichment results revealed that ginseng could regulate multiple aspects of depression through neuroactive ligand-receptor interaction, HIF-1 signaling pathway, and Serotonergic synapse. More importantly, we found that frutinone A and kaempferol are key ingredients in ginseng with dual activities of immune-regulation and anti-depression. Conclusions: We discovered that the therapeutic activities of ginseng for depression mainly involve neurotransmitters, neurotrophic factors, neurogenesis, HPA axis and inflammatory response. Pharmacological network analysis can help to explain the potential effects of ginseng for treating depression, indicating that ginseng is a preferable herb clinically for immune-regulation and anti-depression in post-pandemic.

show abstract

“…Quercetin, a typical avonoid, is one of the major compounds of FF, LIF, EH, HH, PCB, and LI in LHQW capsule and has been reported to have the effects of anti-in ammation, antiviral, strengthening the endothelial barrier integrity and inhibiting the expression of cytokines [31][32][33][34]. Kaempferol is avonoid found in FF, LIF, EH, FBR, HH, and LI of LHQW capsule, and can protect against in ammation, virus infection, endothelial barrier dysfunction, and cytokines release [35][36][37][38]. Another important compounds, such as luteolin, naringenin, and beta-sitosterol, in LHQW capsule also have these protective effects [39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanisms of Lian Hua Qing Wen Capsule against COVID-19 by Network Pharmacology and Molecular Docking Approach

Chen¹,

Qu²,

Tan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease has led to a wide-spread global pandemic. There is no specific antiviral drug proven effective for the treatment of patients with COVID-19 at present. Combination of western and traditional Chinese medicine (TCM) is recommended, and Lian Hua Qing Wen (LHQW) capsule is a basic prescription and widely used to treat COVID-19 in China. However, the mechanisms of LHQW capsule treating COVID-19 are not clear. The aim of the study is to explore the mechanisms of LHQW capsule treating COVID-19 based on network pharmacy and molecular docking approach. Methods The active compounds and targets of LHQW capsule were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). COVID-19 related target genes were obtained from GeneCards database and OMIM database. Protein–protein interaction (PPI) networks of LHQW capsule targets and COVID-19-related genes were visualized and merged to identify the candidate targets for LHQW capsule treating COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed. The hub genes involved in the gene-related pathways were screened and their corresponding compounds were used for in vitro validation of molecular docking predictions.Results A total of 185 active compounds of LHQW capsule were screened out, and 263 targets were predicted. Third hundred and fifty-two COVID-19 related target genes were obtained from GeneCards database and OMIM database. GO functional enrichment analysis showed that the biological processes of LHQW capsule treating COVID-19 were closely linked with the regulation of inflammation, immunity, cytokines production, vascular permeability, oxidative stress and apoptosis. KEGG enrichment analysis revealed that the pathways of LHQW capsule treating COVID-19 were significantly enriched in AGE−RAGE signaling pathway in diabetic complications, Kaposi sarcoma−associated herpesvirus infection, TNF, IL−17, and Toll−like receptor (TLR) signaling pathway. The hub targets genes in the gene-related pathways analysis of LHQW capsule treating COVID-19 included MAPK1, MAPK3, RELA, IL-6 and CASP8, which closely associated with inflammation, cytokines storm and apoptosis. Finally, molecular docking showed that top 5 compounds of LHQW capsule also had good binding activities to the important targets in COVID-19.Conclusions The mechanisms of LHQW capsule treating COVID-19 may involve in inhibiting inflammatory response, cytokine storm and virus infection, and regulating immune reactions, apoptosis and endothelial barrier.

show abstract

Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade

Cited by 86 publications

References 43 publications

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Network pharmacology-based active compounds and pharmacological mechanisms of ginseng for depression in post-COVID-19

Exploring the Mechanisms of Lian Hua Qing Wen Capsule against COVID-19 by Network Pharmacology and Molecular Docking Approach

Contact Info

Product

Resources

About