Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract

This study aimed to assess the potential of <i>Lactuca serriola</i> (Asteraceae) seed <i>n</i>-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were ev...

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Main Authors: Muhammad Ihsan Ullah, Rukhsana Anwar, Shahzad Kamran, Bazgha Gul, Sameh S. Elhady, Fadia S. Youssef
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/11/2232
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author Muhammad Ihsan Ullah
Rukhsana Anwar
Shahzad Kamran
Bazgha Gul
Sameh S. Elhady
Fadia S. Youssef
author_facet Muhammad Ihsan Ullah
Rukhsana Anwar
Shahzad Kamran
Bazgha Gul
Sameh S. Elhady
Fadia S. Youssef
author_sort Muhammad Ihsan Ullah
collection DOAJ
description This study aimed to assess the potential of <i>Lactuca serriola</i> (Asteraceae) seed <i>n</i>-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where <i>n</i>-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially <i>n</i>-hexane extract (400 mg/kg)—which showed 456.14%—increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, <i>L. serriola</i> enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of <i>L. serriola</i> seeds.
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spelling doaj.art-ad02ab5b7988496a8b6becd79260a91b2023-11-24T07:31:52ZengMDPI AGAntioxidants2076-39212022-11-011111223210.3390/antiox11112232Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive ExtractMuhammad Ihsan Ullah0Rukhsana Anwar1Shahzad Kamran2Bazgha Gul3Sameh S. Elhady4Fadia S. Youssef5Punjab University College of Pharmacy, University of the Punjab, Lahore 54000, PakistanPunjab University College of Pharmacy, University of the Punjab, Lahore 54000, PakistanPunjab University College of Pharmacy, University of the Punjab, Lahore 54000, PakistanPunjab University College of Pharmacy, University of the Punjab, Lahore 54000, PakistanDepartment of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Abbasia, Cairo 11566, EgyptThis study aimed to assess the potential of <i>Lactuca serriola</i> (Asteraceae) seed <i>n</i>-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where <i>n</i>-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially <i>n</i>-hexane extract (400 mg/kg)—which showed 456.14%—increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, <i>L. serriola</i> enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of <i>L. serriola</i> seeds.https://www.mdpi.com/2076-3921/11/11/2232<i>Lactuca serriola</i>anxiolyticanticonvulsantepilepsyIndustrial developmentdrug discovery
spellingShingle Muhammad Ihsan Ullah
Rukhsana Anwar
Shahzad Kamran
Bazgha Gul
Sameh S. Elhady
Fadia S. Youssef
Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
Antioxidants
<i>Lactuca serriola</i>
anxiolytic
anticonvulsant
epilepsy
Industrial development
drug discovery
title Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
title_full Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
title_fullStr Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
title_full_unstemmed Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
title_short Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of <i>Lactuca Serriola</i> Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
title_sort evaluation of the anxiolytic and anti epileptogenic potential of i lactuca serriola i seed using pentylenetetrazol induced kindling in mice and metabolic profiling of its bioactive extract
topic <i>Lactuca serriola</i>
anxiolytic
anticonvulsant
epilepsy
Industrial development
drug discovery
url https://www.mdpi.com/2076-3921/11/11/2232
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