<i>Combretum lanceolatum</i>extract reverses anxiety and seizure behavior in adult zebrafish through GABAergic neurotransmission: an<i>in vivo and in silico</i>study

Silva, Antônio Wlisses da; Ferreira, Maria Kueirislene Amâncio; Pereira, Lucas Ramos; Rebouças, Emanuela L.; Coutinho, Marnielle Rodrigues; Dos, Joyce; Lima, Reis; Guedes, Maria Izabel Florindo; Bandeira, Paulo Nogueira; Magalhães, Francisco Ernani Alves; Menezes, Jane Eire Silva Alencar de; Marinho, Márcia Machado; Teixeira, Alexandre Magno Rodrigues; Trevisan, M.; Santos, Hélcio Silva dos; Marinho, Emmanuel Silva

doi:10.1080/07391102.2021.1935322

Cited by 16 publications

(5 citation statements)

References 65 publications

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“…In this work, the reversal of anxiolysis by pretreatment with flumazenil suggests that the anxiolytic effect of the biflavonoid AMT is dependent on the GABA A receptor (Figure 8). This study corroborated the same results obtained from our previous studies, such as Ferreira et al [14] who reported the anxiolytic-like effect of synthetic chalcone, as well as Silva et al [46] who reported that Combretum lanceolatum extract reversed anxiety on aZF with the participation of the GABAergic system.…”

Section: Discussionsupporting

confidence: 92%

“…Adult zebrafish have been used to investigate the potential of new alternative drugs for the treatment of alcohol withdrawal-induced anxiety [14,46,50]. In this context, we employed the same methods to assess the potential of AMT during alcohol withdrawalinduced anxiety in aZF.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between these systems is still not completely understood, but some evidence suggests they can interact and influence each other. For example, the activation of 5HT 3A/3B receptors can modulate GABA release in certain areas of the brain, affecting the activity of the GABAergic system [46].…”

Section: Discussionmentioning

confidence: 99%

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An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

Frota,

da Silva,

Alves

et al. 2024

Receptors

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The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

Frota,

da Silva,

Alves

et al. 2024

Receptors

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“…mentioned that Combretum species are characterized by high flavonoid and phenolic compound levels. To date, a few Combretum species that have been quantified for its total phenolic content, viz., C. leprosum, Combretum micranthum, Combretum lanceolatum, Combretum indicum and Combretum molle (da Silva et al, 2021;Mashi et al, 2021;Forid et al, 2021). These species were found to exhibit high levels of phenolic compounds which correlates to the results obtained from this research.…”

Section: Total Phenolic Contentsupporting

confidence: 82%

The secretory scales and medicinal properties of combretum erythrophyllum.

Bantho

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Medicinal plants are known to contain phytometabolites that could effectively improve an individual’s state of health. Species of Combretum are highly valued in Africa due to the plethora of their traditional medicinal uses. Combretum erythrophyllum. Burch. Sond., commonly known as the river bushwillow, is known to contain medicinally important phytometabolites. Traditionally, the foliage is used to treat venereal diseases and abdominal pain, whilst the bark is used to alleviate sores, infertility, and labour pains. Although C. erythrophyllum has numerous traditional medicinal uses, there is limited scientific knowledge on the micromorphological structures and the associated exudate. Thus, this study aimed to characterize the micromorphological features of leaf and stembark secretory apparatus of C. erythrophyllum, using light and electron microscopy. Furthermore, a histo-phytochemical analysis was conducted to determine the presence and localization of phytometabolites within the trichomes and exudate. The antioxidant, antibacterial, apoptotic and cytotoxic potential of the leaf and stembark extracts were also evaluated. The micromorphological analysis identified the presence of peltate scales and non- glandular trichomes across surfaces. Peltate scales were comprised of a sunken basal cell, bicellular stalk, and a multicellular head. Head cell count appeared to increase upon leaf maturation. The granulocrine pathway was identified as a possible mode of secretion for C. erythrophyllum due to the extensive presence of vesicles, vacuoles, and electron dense material within the peltate scales. Preliminary histo-phytochemical analyses revealed the presence of carbohydrates, sterols, lipids, phenolic compounds, total proteins, alkaloids, and essential oils. Thin-layer chromatography allowed for the visualization of 36 compound classes while gas chromatography-mass spectrometry showed 266 compounds present. Fourier-transform infrared spectroscopy analysis confirmed the presence of phenols, alkenes, amines, alcohols, and esters among many. The antioxidant ability of the generated extracts were evaluated using the 2,2- diphenyl-1-picryl-hydrazyl-hydrate antioxidant assay and Ferric Reducing Antioxidant Power assay. A positive correlation between % inhibition and extract concentrations, was noted in both. In both instances, the methanol stembark extracts performed the best, (Leaf- 5,2866 and Stembark- 4,2866 μg/mL). Furthermore, the results obtained from the total flavonoid assay correlated with the trend observed through the total phenolic assay, whereby methanolic extracts yielded most promising results. Additionally, this study aimed to generate silver nanoparticles using crude extracts. A novel protocol for the synthesis of silver nanoparticles (AgNPs) using the leaf and stembark extracts of C. erythrophyllum was established. The generated AgNPs were characterized and evaluated for its potential antibacterial activity. Methanolic extracts inhibited the growth of Pseudomonas aeruginosa, Bacillus subtilis, Methicillin Resistant Staphylococcus aureus, and Staphylococcus aureus. Lastly, the generated crude extracts displayed promising results when evaluated for their cytotoxic and apoptotic abilities however upon nanoencapsulation the cytotoxic and apoptotic capabilities increased significantly. In correlation with the above, the AgNPs appeared to intensify the overall inhibition activity. Based on the findings of the study, Combretum erythrophyllum has a reservoir of unexplored allopathic potential which could revolutionize the medicinal world.

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“…Several studies on the mechanism of action of anxiolytic compounds in adult zebrafish have used flumazenil to investigate its possible effects through modulation at the binding site of benzodiazepines on the GABAa receptor 68,70,71 . In this study, tests with flumazil were performed to verify its interference in the action of the extract.…”

Section: Discussionmentioning

confidence: 99%

Analysis toxicity by different methods and anxiolytic effect of the aqueous extract Lippia sidoides Cham.

Camilo

Leite

Mendes

et al. 2022

Sci Rep

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Lippia sidoides Cham. (Verbenaceae) is a species often mentioned in traditional medicine due to the medicinal properties attributed to its leaves, which include antibacterial, antifungal, acaricidal and antioxidant. Several of these actions have been scientifically proven, according to reports in the literature; however, little is known about toxicological aspects of this plant. This work included studies to determine the chemical composition and toxicity tests, using several methods aiming to evaluate the safety for use of the aqueous extract of L. sidoides leaves, in addition, the anxiolytic effect on adult zebrafish was investigated, thus contributing to the pharmacological knowledge and traditional medicine concerning the specie under study. The chemical profile was determined by liquid chromatography coupled to mass spectrometry-HPLC/MS with electrospray ionization. Toxicity was evaluated by zebrafish, Drosophila melanogaster, blood cells, and Artemia salina models. 12 compounds belonging to the flavonoid class were identified. In the toxicity assays, the observed results showed low toxicity of the aqueous extract in all tests performed. In the analysis with zebrafish, the highest doses of the extract were anxiolytic, neuromodulating the GABAa receptor. The obtained results support the safe use of the aqueous extract of L. sidoides leaves for the development of new drugs and for the use by populations in traditional medicine.

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Combretum lanceolatumextract reverses anxiety and seizure behavior in adult zebrafish through GABAergic neurotransmission: anin vivo and in silicostudy

Cited by 16 publications

References 65 publications

An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

The secretory scales and medicinal properties of combretum erythrophyllum.

Analysis toxicity by different methods and anxiolytic effect of the aqueous extract Lippia sidoides Cham.

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