Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
BMC Complement Med Ther. 2023 Aug 22;23(1):294. doi: 10.1186/s12906-023-04125-2.
Amyloid-β (Aβ) plays an essential role in the development of the early stage of Alzheimer's disease (AD). Asiatic acid (AA), an active compound in Centella asiatica L, exhibit neuroprotective properties in previous studies. Due to its low bioavailability, the nose-to-brain delivery technique was used to enhance AA penetration in the brain. In this study, AA was also loaded in solid lipid nanoparticles (SLNs) as a strategy to increase its absorption in the nasal cavity.
Memory impairment was induced via direct intracerebroventricular injection of Aβ oligomer into mouse brain. The neuroprotective effect and potential underlying mechanisms were investigated using several memory behavioral examinations and molecular techniques.
The intranasal administration of AA in SLNs attenuated learning and memory impairment induced by Aβ in Morris water maze and novel object recognition tests AA significantly inhibited tau hyperphosphorylation of pTau-S396 and pTau-T231 and prevented astrocyte reactivity and microglial activation in the hippocampus of Aβ-treated mice. It is also decreased the high levels of IL-1β, TNF-α, and malondialdehyde (MDA) in mouse brain.
These results suggested that nose-to-brain delivery of AA in SLNs could be a promising strategy to treat the early stage of AD.
淀粉样蛋白-β（Aβ）在阿尔茨海默病（AD）早期阶段的发展中起关键作用。积雪草酸（AA）是积雪草中的一种活性化合物，先前的研究表明其具有神经保护作用。由于其生物利用度低，因此采用鼻内递药技术增强 AA 在大脑中的穿透性。在本研究中，AA 也被负载于固体脂质纳米粒（SLNs）中，以增加其在鼻腔中的吸收。
通过直接向小鼠脑内侧脑室注射 Aβ寡聚体诱导记忆障碍。使用几种记忆行为测试和分子技术研究了 AA 的神经保护作用及其潜在机制。
AA 在 SLNs 中的鼻内给药可减轻 Aβ在 Morris 水迷宫和新物体识别测试中引起的学习和记忆障碍。AA 显著抑制了 Aβ 处理小鼠海马中 pTau-S396 和 pTau-T231 的 tau 过度磷酸化，并阻止了星形胶质细胞反应性和小胶质细胞活化。它还降低了小鼠大脑中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和丙二醛（MDA）的高表达。
这些结果表明，通过 SLNs 将 AA 鼻内递药可能是治疗 AD 早期阶段的一种有前途的策略。
