In Silico and In Vivo: Evaluating the Therapeutic Potential of Kaempferol, Quercetin, and Catechin to Treat Chronic Epilepsy in a Rat Model

Ahmed, Hammad; Khan, Mahtab Ahmad; Zaidi, Syed Awais Ali; Muhammad, Sajjad

doi:10.3389/fbioe.2021.754952

Cited by 21 publications

(17 citation statements)

References 70 publications

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“…It is noteworthy that flavonoids have similar structures to benzodiazepines and can be developed as an alternative to antiepileptic drugs. Kaempferol and quercetin showed the same antiepileptic effect level as levetiracetam in the treatment of rat chronic epilepsy model and also showed the regulating pro-inflammatory and anti-inflammatory factors [ 21 ]. Formononetin has anti-cancer, hypolipidemic and neuroprotective effects.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Sun

et al. 2022

PLoS ONE

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Purpose To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network Methods Modern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection. Results Forty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test. Conclusion LTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.

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Section: Discussionmentioning

confidence: 99%

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Sun

et al. 2022

PLoS ONE

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“…Moreover, seizure prevention by quercetin was reported in PTZ‐induced seizure model (Sefil et al, 2014). Furthermore, Ahmed et al (2021) demonstrated the effective role of quercetin, kaempferol, and catechin in reducing epileptic seizures in terms of the number, intensity, onset time, mean seizure duration, and percentage protection of seizures that were ameliorated compared to levetiracetam drug in chronic epilepsy rat model (Ahmed et al, 2021). In addition, daidzein present only in TN extract only demonstrated notable anti‐epileptic properties as it ameliorated seizure scores in the PTZ‐kindled mice via modulation of brain‐derived neurotrophic factor and vascular endothelial growth factor, oxidative stress, and apoptotic signaling in the brain (Kazmi et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

“…This effect was blocked with flumazenil suggesting GABA-A modulatory effects of ferulic acid (Machado et al, 2015). Interestingly, quercetin, a flavonoid present in high concentration in TN extract, was reported to act as an antagonist of the NMDA receptor (Cheng et al, 2006) (Ahmed et al, 2021). In addition, daidzein present only in TN extract only demonstrated notable anti-epileptic properties as it ameliorated seizure scores in the PTZ-kindled mice via modulation of brain-derived neurotrophic factor and vascular endothelial growth factor, oxidative stress, and apoptotic signaling in the brain (Kazmi et al, 2020).…”

Section: Anticonvulsant Activitymentioning

confidence: 99%

HPLC and GC–MS–based metabolic profiles and in vivo anticonvulsant, sedative, and antinociceptive potentials of truffles Tirmania nivea and Tirmania pinoyi hydromethanolic extracts in mice

Aboutabl

Elkhateeb

Masoud

et al. 2022

Biomedical Chromatography

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GC-MS and HPLC analyses of the hydromethanolic extracts of the truffles Tirmania nivea (TN) and Tirmania pinoyi (TP) revealed the presence of 18 metabolites and 11 polyphenols, respectively. In vivo, TP extract protected against subcutaneous pentylenetetrazole (scPTZ) and maximal electric shock (MES)-induced convulsions faster than TN extract. TP extract (100 and 300 mg/kg) showed 100% protection and longer duration than TN extract in the scPTZ test. Similarly, at 300 mg/kg, TP demonstrated a quicker start (75%) and longer duration of action (100%) than TN in MES test. In the scPTZ test, ED 50 of TP demonstrated greater anticonvulsant efficacy than that of TN. In mice given TP and TN treatments, the brain GABA levels noticeably increased. TP (100 and 300 mg/kg) produced a notable sedative effect in open-field test, whereas TN (100 or 300 mg/kg) and TP (300 mg/kg) reduced sleep latency by 52%, 45%, and 79%, respectively. In writhing test, TN (100 or 300 mg/kg) significantly enhanced analgesic efficacy by 50 and 87%, respectively.Comparatively, in formalin test, TP and TN at a dosage of 300 mg/kg decreased the length of the licking by 34 and 59%, respectively. For the first time, this study explains the anticonvulsant, sedative, central, and peripheral analgesic activities of truffle extracts.

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“…Quercetin and kaempferol, both phytoflavonoids, are important dietary components of fruits and vegetables and have various biological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. In vivo studies have shown that these phytoflavonoids can modulate the immune response, becoming an important treatment alternative for epilepsy [ 24 ]. GABA exists widely in the mammalian brain and is the main inhibitory neurotransmitter.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking to Explore the Mechanism of Kangxian Decoction for Epilepsy

Wang

Zhang

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Purpose. Kangxian decoction (KXD) has been used in clinical practice to treat epilepsy. The purpose of this study was to explore the active components of KXD and clarify its antiepileptic mechanism through network pharmacology and molecular docking. Methods. The components of KXD were collected from the Encyclopedia of Traditional Chinese Medicine (ETCM) database and the literature was searched. Then, active ingredients were screened by SwissADME and potential targets were predicted by the SwissTargetPrediction database. Epilepsy-related differentially expressed genes were downloaded from the Gene Expression Omnibus database. A component-target-pathway network was constructed with Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‒protein interaction network analysis revealed the potential mechanism and critical targets. Receiver operating characteristic (ROC) curves and box plots in microarray data validated the good diagnostic value and significant differential expression of these critical genes. Molecular docking verified the association between active ingredients and essential target proteins. Results. In our study, we screened the important compounds of KXD for epilepsy, including quercetin, baicalin, kaempferol, yohimbine, geissoschizine methyl ether, baicalein, etc. KXD may exert its therapeutic effect on epilepsy through the following targets: PTGS2, MMP9, CXCL8, ERBB2, and ARG1, acting on the following pathways: neuroactive ligand-receptor interactions, arachidonic acid metabolism, IL-17, TNF, NF-kappa B, and MAPK signaling pathways. The molecular docking results showed that the active ingredients in KXD exhibited good binding ability to the key targets. Conclusion. In this study, we explored the possibility that KXD for epilepsy may act on multiple targets through multiple active ingredients, involving neurotransmitters and neuroinflammatory pathways, providing a theoretical basis for subsequent clinical and experimental studies that will help develop effective new drugs to treat epilepsy.

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In Silico and In Vivo: Evaluating the Therapeutic Potential of Kaempferol, Quercetin, and Catechin to Treat Chronic Epilepsy in a Rat Model

Cited by 21 publications

References 70 publications

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

HPLC and GC–MS–based metabolic profiles and in vivo anticonvulsant, sedative, and antinociceptive potentials of truffles Tirmania nivea and Tirmania pinoyi hydromethanolic extracts in mice

Network Pharmacology and Molecular Docking to Explore the Mechanism of Kangxian Decoction for Epilepsy

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