Quercetin abrogates lipopolysaccharide-induced depressive-like symptoms by inhibiting neuroinflammation via microglial NLRP3/NFκB/iNOS signaling pathway

Adeoluwa, Olusegun; Olayinka, Juliet N; Adeoluwa, Gladys; Akinluyi, Elizabeth Toyin; Adeniyi, Funmilayo; Fafure, Adedamola Adediran; Nebo, Kate Eberechukwu; Edem, Edem Ekpenyong; Eduviere, Anthony T.; Abubakar, Bawa

doi:10.1016/j.bbr.2023.114503

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…Sophocarpine, another leukotriene receptor antagonist, signi cantly inhibited the alteration in TBARS in LPS-induced lung injury ( Lu et al, 2019). Parallel to our ndings, other studies suggested that anti-in ammatory agents can inhibit both the in ammatory and the oxidative stress in different organ injuries, such as sophocarpine (Lu et al, 2019), ulinastatin in LPS-induced acute lung injury (Cao et al, 2018), resolvin D1 in experimental acute pancreatitis and associated lung injury , and quercetin in LPS-induced depressive-like symptoms by inhibiting neuroin ammation via modulation of NFκB/iNOS signaling pathway ( Adeoluwa, et al, 2023).…”

Section: Discussionsupporting

confidence: 84%

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats

Hagar

Alhazmi

Arafa

2023

Preprint

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Purpose The purpose of this study is to investigate the effect of montelukast on lipopolysaccharide (LPS)-induced pancreatitis. Methods Acute pancreatitis was induced by a single dose of LPS (6 mg/kg, i.p.) while montelukast was given in two different doses (10 and 20 mg/kg/day) for three consecutive days prior to injection of LPS. Results Acute pancreatitis was demonstrated by significant increases in serum levels of pancreatic enzymes lipase and amylase and lactate dehydrogenase (LDH). Proinflammatory response activation was evident by elevated serum levels of nitric oxide (NO) and increased pancreatic concentrations of tumor necrosis factor- α (TNF-α), interleukin-1 (IL-1β) and intercellular adhesion molecule-1 (ICAM-1). The activity of myeloperoxidase (MPO), a neutrophil infiltration marker, has also been increased. Oxidative stress was confirmed by significant increases in the concentrations of lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) and decreases in the concentrations of reduced glutathione (GSH) in the pancreatic tissues of animals treated with LPS. Histological examination confirmed the biochemical alterations. Montelukast treatment reversed all these biochemical indices and histopathological changes that were induced by LPS. Montelukast reduced the increase in serum levels of lipase, amylase, LDH, total nitrite/nitrate, TNF-α, IL-1β and ICAM-1. MPO activities and TBARS concentrations were also suppressed while GSH content was increased in pancreatic tissues. Conclusion These results show that montelukast may be a useful pharmacological agent in protection against LPS-induced oxidative pancreatic injury by inhibiting neutrophil infiltration, counteracting oxidative stress, and suppressing inflammatory mediators.

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Section: Discussionsupporting

confidence: 84%

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats

Hagar

Alhazmi

Arafa

2023

Preprint

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“…Accumulating evidence has demonstrated that peripheral administration of LPS culminates in a distinct depressive-like behavioral syndrome, measured by the classical behavior tests [23,24]. The LPS signi cantly decreased mobility of rats in FST and decreased sucrose preference, which is indicative of depressive-like behaviours [25]. The depressive like behaviors were revered by taVNS treatment, indicates that taVNS has signi cant anti-depressant effect on depressive-like rats.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-like Behavior by Regulating Central α7nAChR/JAK2 Signaling

wang,

Wang,

Chen

et al. 2023

Preprint

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Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous Auricular Vagus Stimulation(taVNS), as a non-invasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to Control group, LPS group, taVNS + LPS group and the same as the α7 nicotinic acetylcholine chloride receptor(α7nAChR) (-/-) gene knockout rats. The expressions of tumor necrosis factor-alpha (TNF-ɑ) and phosphorylated-Janus kinase2(p-JAK2),phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala and hippocampus were detected by Western Blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of corssing and reaing in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (-/-) gene knockout rats. The expression of TNF-ɑ signifciantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the above-mentioned phenomena but had rare improvement effect for α7nAChR(-/-) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.

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“…Quercetin, the most abundant flavonoid in various fruits and vegetables, exerts good neuroprotective effects due to its ability to cross the blood-brain barrier ( Silvestro et al, 2021 ). Adeoluwa et al (2023) , in a study involving lipopolysaccharide (LPS) induced neuroinflammation in rats, indicated that quercetin could significantly attenuate the expression of inflammasomes, inducible NOS, NF-κB, proinflammatory cytokines, and microglia cells in the hippocampus and prefrontal cortex, thus presenting antidepressant-like property. Similar results were reported by Fang et al (2019) , wherein quercetin could mitigate LPS-induced depression in rats via regulating brain-derived neurotrophic factor (BDNF) related variance expression of Copine 6 and TREM1/2 in the hippocampus and prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression

Jain,

Tailang,

Chandrasekaran

et al. 2024

Front. Pharmacol.

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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.

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Quercetin abrogates lipopolysaccharide-induced depressive-like symptoms by inhibiting neuroinflammation via microglial NLRP3/NFκB/iNOS signaling pathway

Cited by 7 publications

References 43 publications

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats

Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-like Behavior by Regulating Central α7nAChR/JAK2 Signaling

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression

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