Facultad de Química Farmacéutica Biológica, Universidad Veracruzana, Xalapa, Veracruz, México.
Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, México.
BMC Complement Med Ther. 2023 Sep 27;23(1):343. doi: 10.1186/s12906-023-04179-2.
Status epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures.
Twenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated.
Centella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments.
The dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.
癫痫持续状态（SE）是一种癫痫活动类型，其特征是抑制机制失效，而抑制机制主要由 GABA 能系统调节。这种失衡会增加谷氨酸能神经传递，从而产生癫痫活动。它还与氧化应激有关，因为活性氧（ROS）和抗氧化防御之间的平衡被打破。不幸的是，长期使用抗癫痫药物（AEDs）可能会产生肝毒性、肾毒性和血液学改变。在这种情况下，一些植物的次生代谢物已被用于通过抗氧化特性来改善神经系统疾病的恶化，除了其抗惊厥作用。一个例子是积雪草，这种植物因其抗氧化活性而被认为具有神经保护作用。然而，与传统药物类似，当以高剂量使用时，天然分子可能会产生副作用，而积雪草可能会出现这种情况。因此，我们旨在评估具有已证实的抗惊厥活性的积雪草标准化提取物对锂/匹罗卡品诱导的癫痫发作大鼠的生化和血液学参数的影响。
将 28 只成年雄性 Wistar 大鼠随机分为四组（每组 n=7）：载体（纯净水）、积雪草（200 和 400mg/kg）和卡马西平（CBZ）（300mg/kg）作为抗惊厥活性的药理学对照。治疗每天口服给药，连续 35 天。在第 36 天，使用锂/匹罗卡品模型（3 mEq/kg，腹腔内注射和 30mg/kg 皮下注射）诱导 SE，并评估行为和生化效应。
积雪草 400mg/kg 增加了首次全身性癫痫发作和 SE 发作的潜伏期，并与载体组相比显著减少了首次全身性癫痫发作的时间。生化参数，即血液细胞学、血液化学和肝功能测试，在不同治疗组之间没有显著差异。
在没有肝毒性、肾毒性和血液学参数改变的情况下，产生抗惊厥活性的积雪草剂量表明，这种植物的标准化提取物可能对开发治疗癫痫相关惊厥的新的安全疗法有用。
