Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats

Abstract Background Recurrent seizure is synchronous neuronal network hyperexcitation. Even though many anti-epileptic drugs (AEDs) are available, but have several drawbacks, including multiple drug interactions, suboptimal response rates, significant adverse effects, and a narrow therapeutic index....

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Main Author: Mohamed A. Alblihed
Format: Article
Language:English
Published: SpringerOpen 2023-12-01
Series:Beni-Suef University Journal of Basic and Applied Sciences
Subjects:
Online Access:https://doi.org/10.1186/s43088-023-00425-1
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author Mohamed A. Alblihed
author_facet Mohamed A. Alblihed
author_sort Mohamed A. Alblihed
collection DOAJ
description Abstract Background Recurrent seizure is synchronous neuronal network hyperexcitation. Even though many anti-epileptic drugs (AEDs) are available, but have several drawbacks, including multiple drug interactions, suboptimal response rates, significant adverse effects, and a narrow therapeutic index. Trichoderma is a biocontrol agent which maintains stress-related gene expression to adapt to unstable environmental conditions. The current study sought to delineate the ameliorative effects of metabolites of Trichoderma harzianum (T. harzianum) culture filtrate (ThCF) by assessing the functions of T regulatory cells and rebalancing oxidative stress. Methods Experimental rats were divided into control, epileptic, valproic acid-treated, and T. harzianum cultured filtrate (ThCF). Lipid peroxidation, nitric oxide, and antioxidant defense enzymes were estimated. Moreover, interleukins-6, -10, -17, tumor necrosis factor (TNF-α), and transforming growth factor (TGF-β) were estimated using ELISA kits, in addition to T-reg markers; cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and forkhead box P3 (FOXP3) were estimated by qRT-PCR. Results Data revealed that the T. harzianum cultured filtrate (ThCF) retarded the lipid oxidation rate and has antioxidant activities, as well as increased levels of GPx, CAT, and SOD. Moreover, ThCF re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusion Trichoderma harzianum has a potent antioxidant activity with high capacity to scavenge ROS and downregulate all T-reg markers. Therefore, the present data are directed toward the characterization of new active constituents of secondary metabolites of T. harzianum with significant therapeutic functions in several diseases. The promising findings may suggest more clinical and experimental scenarios to reduce AED’s drawbacks and side effects.
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spelling doaj.art-c7916a0da6b44c1191f79e3bc49ea1bd2023-12-10T12:28:13ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432023-12-0112111210.1186/s43088-023-00425-1Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic ratsMohamed A. Alblihed0Department of Medical Microbiology, College of Medicine, Taif UniversityAbstract Background Recurrent seizure is synchronous neuronal network hyperexcitation. Even though many anti-epileptic drugs (AEDs) are available, but have several drawbacks, including multiple drug interactions, suboptimal response rates, significant adverse effects, and a narrow therapeutic index. Trichoderma is a biocontrol agent which maintains stress-related gene expression to adapt to unstable environmental conditions. The current study sought to delineate the ameliorative effects of metabolites of Trichoderma harzianum (T. harzianum) culture filtrate (ThCF) by assessing the functions of T regulatory cells and rebalancing oxidative stress. Methods Experimental rats were divided into control, epileptic, valproic acid-treated, and T. harzianum cultured filtrate (ThCF). Lipid peroxidation, nitric oxide, and antioxidant defense enzymes were estimated. Moreover, interleukins-6, -10, -17, tumor necrosis factor (TNF-α), and transforming growth factor (TGF-β) were estimated using ELISA kits, in addition to T-reg markers; cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and forkhead box P3 (FOXP3) were estimated by qRT-PCR. Results Data revealed that the T. harzianum cultured filtrate (ThCF) retarded the lipid oxidation rate and has antioxidant activities, as well as increased levels of GPx, CAT, and SOD. Moreover, ThCF re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusion Trichoderma harzianum has a potent antioxidant activity with high capacity to scavenge ROS and downregulate all T-reg markers. Therefore, the present data are directed toward the characterization of new active constituents of secondary metabolites of T. harzianum with significant therapeutic functions in several diseases. The promising findings may suggest more clinical and experimental scenarios to reduce AED’s drawbacks and side effects.https://doi.org/10.1186/s43088-023-00425-1EpilepsyTrichoderma harzianumLipid peroxidationAntioxidantsT-regulatory cells
spellingShingle Mohamed A. Alblihed
Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
Beni-Suef University Journal of Basic and Applied Sciences
Epilepsy
Trichoderma harzianum
Lipid peroxidation
Antioxidants
T-regulatory cells
title Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
title_full Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
title_fullStr Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
title_full_unstemmed Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
title_short Metabolites of Trichoderma harzianum re-balance T-reg/Th-17 cytokine axis in epileptic rats
title_sort metabolites of trichoderma harzianum re balance t reg th 17 cytokine axis in epileptic rats
topic Epilepsy
Trichoderma harzianum
Lipid peroxidation
Antioxidants
T-regulatory cells
url https://doi.org/10.1186/s43088-023-00425-1
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