Fu Huan, Xu Zhen, Zhang Xi-le, Zheng Guo-Qing
Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Front Neurosci. 2020 Jan 14;13:1421. doi: 10.3389/fnins.2019.01421. eCollection 2019.
Alzheimer's disease (AD), the most common cause of dementia, is highly prevalent worldwide with no modifying therapy. Behavioral and psychological symptoms of dementia (BPSD) occur in most patients with AD, and depression is one of the most common AD-related BPSD. Kaixinsan (KXS) is an ancient Chinese herbal prescription widely used to treat dementia and forgetfulness. In this systematic review, we conducted a meta-analysis to assess preclinical evidence for the effects of KXS on cognitive impairment and depression. Thirty-eight articles involving 1,050 animals were included after searching from six databases from the inception up to June 2019. The primary outcome measures were behavioral outcome. Indicators of cognitive function in AD included escape latency, time spent on the target quadrant, and the number of target platform crossings in the Morris water maze (MWM) test. Indicators of depression included number of rearing events and total distance in the open-field test, duration of immobility in the forced swim test, and sucrose consumption or sucrose preference index in the sucrose preference test. The secondary outcomes were mechanisms of KXS for treatment of AD and depression. The results showed that KXS significantly reduced escape latency ( < 0.01), increased time spent in the target quadrant ( < 0.01), and increased the number of target platform crossings ( < 0.01) in the MWM test in AD models compared with control. The possible mechanisms for KXS-mediated improvements in cognitive function were antioxidant activity, anti-inflammatory activity, antiapoptotic activity, neuroprotection, and synapse protection. In addition, the results demonstrated that KXS significantly increased the number of rearing instances ( < 0.01) in the open-field test, decreased the duration of immobility ( < 0.01) in forced swim test, and increased sucrose consumption or sucrose preference index ( < 0.01) in the sucrose preference test in depression models compared with control. The mechanisms of KXS-mediated anti-depressive effects were HPA axis regulation, antioxidant activity, anti-inflammatory activity, synapse protection, and neuroprotection. The results of this study suggested that KXS can be used to effectively treat AD and depression through multiple mechanisms, extrapolating the therapeutic potential of KXS for treating AD-related BPSD.
阿尔茨海默病（AD）是痴呆最常见的病因，在全球范围内高度流行且尚无改善疗法。痴呆的行为和心理症状（BPSD）在大多数AD患者中都会出现，而抑郁是最常见的与AD相关的BPSD之一。开心散（KXS）是一种古老的中药方剂，广泛用于治疗痴呆和健忘。在本系统评价中，我们进行了一项荟萃分析，以评估KXS对认知障碍和抑郁影响的临床前证据。从建库至2019年6月，从6个数据库中检索出38篇涉及1050只动物的文章。主要结局指标为行为学结果。AD认知功能指标包括Morris水迷宫（MWM）试验中的逃避潜伏期、在目标象限停留的时间以及穿越目标平台的次数。抑郁指标包括旷场试验中的直立次数和总路程、强迫游泳试验中的不动时间以及蔗糖偏好试验中的蔗糖消耗量或蔗糖偏好指数。次要结局为KXS治疗AD和抑郁的机制。结果显示，与对照组相比，KXS在AD模型的MWM试验中显著缩短了逃避潜伏期（<0.01），增加了在目标象限停留的时间（<0.01），并增加了穿越目标平台的次数（<0.01）。KXS介导认知功能改善的可能机制为抗氧化活性、抗炎活性、抗凋亡活性、神经保护和突触保护。此外，结果表明，与对照组相比，KXS在抑郁模型的旷场试验中显著增加了直立次数（<0.01），在强迫游泳试验中缩短了不动时间（<0.01），并在蔗糖偏好试验中增加了蔗糖消耗量或蔗糖偏好指数（<0.01）。KXS介导抗抑郁作用的机制为下丘脑-垂体-肾上腺（HPA）轴调节、抗氧化活性、抗炎活性、突触保护和神经保护。本研究结果提示，KXS可通过多种机制有效治疗AD和抑郁，推断了KXS治疗AD相关BPSD的治疗潜力。
