Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
BMC Complement Med Ther. 2022 Apr 19;22(1):108. doi: 10.1186/s12906-022-03591-4.
Alzheimer's disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models.
This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aβ protein levels, and neuroinflammation in Aβ-induced rats.
Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aβ, CB + Aβ CHRE125 + Aβ, CHRE250 + Aβ, and CHRE500 + Aβ. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aβ at a concentration of 1 μg/μl were injected into both lateral ventricles (1 μl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aβ protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) were investigated in the cerebral cortex and hippocampus.
Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aβ protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex.
This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aβ protein levels and neuroinflammation caused by Aβ.
阿尔茨海默病（AD）的发病机制与淀粉样蛋白-β（Aβ）诱导的神经炎症有关。在 AD 中，Aβ 积累引起的小胶质细胞激活会导致促炎细胞因子（包括白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNFα））的合成和释放，最终导致认知障碍。吴茱萸（CH）是芸香科的一种药用植物，民间用于治疗胃痛、头痛等疾病，并作为保健品。有趣的是，CH 根提取物（CHRE）具有多种抗炎和其他药理活性，但在 AD 样动物模型中尚无研究。
本研究旨在评估 CHRE 对 Aβ 诱导的大鼠认知障碍、Aβ 蛋白水平升高和神经炎症的影响。
将 48 只成年雄性 Sprague-Dawley 大鼠（250-300g）随机分为 6 组（每组 8 只）：假手术对照、V+Aβ、CB+Aβ、CHRE125+Aβ、CHRE250+Aβ 和 CHRE500+Aβ。用羧甲基纤维素钠、西乐葆（10mg/kgBW）和 CHRE（125、250 和 500mg/kgBW）口服或不给予任何治疗 35 天。第 21 天，将浓度为 1μg/μl 的聚集 Aβ 注入所有处理大鼠的两侧侧脑室（每侧 1μl），而未处理的大鼠则注入无菌生理盐水。10 天后，进行新物体识别测试以评估它们的识别记忆。在测试期末，用过量的硫喷妥钠（120mg/kgBW）和心脏灌流 0.9%生理盐水处死所有大鼠。然后检测大脑皮质和海马中 Aβ 蛋白水平和炎症标志物（CD11b 阳性小胶质细胞、IL-1β 和 TNFα）的表达。
用 CHRE 预处理所有剂量都能减轻短期和长期的认知障碍。此外，CHRE 还抑制了两个脑区 Aβ 蛋白水平和炎症标志物表达的增加，以及西乐葆的作用。
这表明 CHRE 的预防性治疗可能是一种通过降低 Aβ 蛋白水平和 Aβ 引起的神经炎症来治疗认知障碍的潜在疗法。
