Kang Hyun-Bae, Kim Shin-Hye, Uhm Sun-Ho, Kim Do-Kyung, Lee Nam-Seob, Jeong Young-Gil, Sung Nak-Yun, Kim Dong-Sub, Han In-Jun, Yoo Young-Choon, Han Seung-Yun
Department of Anatomy, College of Medicine, Konyang University, Daejeon 35365, Korea.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
Curr Issues Mol Biol. 2022 Jan 8;44(1):257-272. doi: 10.3390/cimb44010019.
Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.
血管性痴呆（VaD）的特征是随时间发展的记忆缺陷，且基本上与神经炎症证据相关。因此，具有抗炎特性的富含多酚的天然植物受到了广泛的科学关注。本研究调查了李子叶提取物（PFL）对VaD是否具有治疗效果。将Sprague Dawley大鼠分为五组：SO组，假手术并给予赋形剂治疗；OP组，手术并给予赋形剂治疗；PFL-L组，手术并给予低剂量（30 mg/kg）PFL治疗；PFL-M组，手术并给予中剂量（60 mg/kg）PFL治疗；PFL-H组，手术并给予高剂量（90 mg/kg）PFL治疗。采用双血管闭塞和低血容量（2VO/H）作为VaD的手术模型，在围手术期口服PFL，持续23天。对大鼠进行Y迷宫、巴恩斯迷宫和被动回避试验，并对其大脑进行组织学研究。OP组表现出与VaD相关的记忆缺陷、海马神经元死亡和小胶质细胞激活；然而，PFL治疗组在上述所有参数上均表现出显著改善。使用脂多糖（LPS）刺激的BV-2细胞（一种小鼠小胶质细胞系），我们测量了PFL介导的一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）产生的变化，以及它们上游的丝裂原活化蛋白激酶（MAPKs）/核因子κB（NFκB）/诱导型一氧化氮合酶（iNOS）的活性。PFL预处理12小时可全面且显著逆转LPS诱导的NO、TNF-α和IL-6产生以及MAPKs/NFκB/iNOS活性的上调。这表明PFL可通过减轻神经炎症来对抗与VaD相关的结构和功能恶化。
