Phytochemistry and Phytopharmacology Division, KSCSTE-Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Pacha-Palode, Thiruvananthapuram, 695562, Kerala, India.
University of Kerala, Thiruvananthapuram, 695034, Kerala, India.
Mol Neurobiol. 2024 Jun;61(6):3296-3313. doi: 10.1007/s12035-023-03741-w. Epub 2023 Nov 21.
Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood-brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from Bacopa monnieri and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (P < 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.
治疗方法有限，以控制癫痫发作，癫痫发作是许多神经病理学的过渡阶段。由于血脑屏障（BBB）的存在，治疗方法有限。草药纳米颗粒制剂可用于增强癫痫预后。从益智中分离出 Bacoside A (BM3) 和 bacopaside I (BM4)，并分别合成纳米颗粒（BM3NP 和 BM4NP），以建立有效的递药系统来缓解癫痫发作和相关疾病。进行物理化学特性分析后，在小鼠神经干细胞（mNSC）和神经母细胞瘤细胞（N2a）上评估细胞活力。然后，在体外测定抗癫痫作用、线粒体膜电位（MMP）、凋亡、免疫染色和癫痫标志物 mRNA 表达。在原代培养的皮质脑电图（EEG）、肌电图（EMG）、非快速眼动（NREM）和快速眼动（REM）睡眠中监测体内 KA 诱导的大鼠癫痫模型中的癫痫发作诱导变化。纳米颗粒在 N2a 细胞中具有超过 50%的细胞活力，IC50 值分别为 1609 和 2962 µg/mL。同样，这些纳米颗粒降低了 N2a 细胞在 KA 处理后的细胞毒性。纳米颗粒降低了癫痫标志物如 fractalkine、HMGB1、FOXO3a 和促炎细胞因子的表达（P < 0.05）。它们保护神经元免受凋亡并恢复 MMP。BM3NPs 和 BM4NPs 给药后，KA 处理大鼠的癫痫发作波显著减少，睡眠潜伏期缩短，NREM 睡眠持续时间增加。结果表明 BM3NPs 和 BM4NPs 具有中和神经元中 KA 诱导的兴奋性毒性癫痫发作的潜力。
