Abd El-Rahman Atef A, El-Shafei Sally M A, Shehab Gaber M G, Mansour Lamjed, Abuelsaad Abdelaziz S A, Gad Rania A
Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minya 61519, Egypt.
Department of Biochemistry, Faculty of Agriculture, Cairo University, Giza 12613, Egypt.
Life (Basel). 2023 Aug 28;13(9):1815. doi: 10.3390/life13091815.
Epilepsy is a serious chronic neurological disorder, which is accompanied by recurrent seizures. Repeated seizures cause physical injuries and neuronal dysfunction and may be a risk of cancer and vascular diseases. However, many antiepileptic drugs (AEDs) have side effects of mood alteration or neurocognitive function, a reduction in neuron excitation, and the inhibition of normal activity. Therefore, the present study aimed to evaluate the effect of secondary metabolites of cultural filtrate (ThCF) when adjusting different electrolytes and neurotransmitters in the hippocampus of epileptic rats.
Cytotoxicity of ThCF against LS-174T cancer cells was assessed using a sulforhodamine B (SRB) assay. Quantitative estimation for some neurotransmitters, electrolytes in sera or homogenate of hippocampi tissues, and mRNA gene expression for ion or voltage gates was assessed by quantitative Real-Time PCR.
Treatment with ThCF reduces the proliferative percentage of LS-174T cells in a concentration-dependent manner. ThCF administration improves hyponatremia, hyperkalemia, and hypocalcemia in the sera of the epilepticus model. ThCF rebalances the elevated levels of many neurotransmitters and reduces the release of GABA and acetylcholine-esterase. Also, treatments with ThCF ameliorate the downregulation of mRNA gene expression for some gate receptors in hippocampal homogenate tissues and recorded a highly significant elevation in the expression of SCN1A, CACNA1S, and NMDA.
Secondary metabolites of Trichoderma (ThCF) have cytotoxic activity against LS-174T (colorectal cancer cell line) and anxiolytic-like activity through a GABAergic mechanism of action and an increase in GABA as inhibitory amino acid in the selected brain regions and reduced levels of NMDA and DOPA. The present data suggested that ThCF may inhibit intracellular calcium accumulation by triggering the NAADP-mediated Ca signaling pathway. Therefore, the present results suggested further studies on the molecular pathway for each metabolite of ThCF, e.g., 6-pentyl-α-pyrone (6-PP), harzianic acid (HA), and hydrophobin, as an alternative drug to mitigate the side effects of AEDs.
癫痫是一种严重的慢性神经系统疾病，伴有反复发作的癫痫发作。反复的癫痫发作会导致身体损伤和神经元功能障碍，并且可能存在患癌症和血管疾病的风险。然而，许多抗癫痫药物（AEDs）具有情绪改变或神经认知功能方面的副作用，会降低神经元兴奋性并抑制正常活动。因此，本研究旨在评估培养滤液的次生代谢产物（ThCF）在调节癫痫大鼠海马体中不同电解质和神经递质时的作用效果。
使用磺酰罗丹明B（SRB）测定法评估ThCF对LS - 174T癌细胞的细胞毒性。通过定量实时PCR评估血清或海马体组织匀浆中某些神经递质、电解质的定量估计以及离子或电压门控的mRNA基因表达。
ThCF处理以浓度依赖的方式降低了LS - 174T细胞的增殖百分比。给予ThCF可改善癫痫模型血清中的低钠血症、高钾血症和低钙血症。ThCF使许多神经递质的升高水平恢复平衡，并减少γ-氨基丁酸（GABA）和乙酰胆碱酯酶的释放。此外，ThCF处理改善了海马体匀浆组织中某些门控受体的mRNA基因表达下调，并记录到SCN1A、CACNA1S和N - 甲基 - D - 天冬氨酸（NMDA）表达的高度显著升高。
木霉菌的次生代谢产物（ThCF）对LS - 174T（结肠癌细胞系）具有细胞毒性活性，并通过GABA能作用机制具有抗焦虑样活性，且在选定脑区中作为抑制性氨基酸的GABA增加，NMDA和多巴胺（DOPA）水平降低。目前的数据表明，ThCF可能通过触发烟酰胺腺嘌呤二磷酸核糖（NAADP）介导的钙信号通路来抑制细胞内钙积累。因此，目前的结果表明需要进一步研究ThCF的每种代谢产物（例如6 - 戊基 - α - 吡喃酮（6 - PP）、哈茨酸（HA）和疏水蛋白）的分子途径，作为减轻AEDs副作用的替代药物。
