Administration of Momordica charantia Enhances the Neuroprotection and Reduces the Side Effects of LiCl in the Treatment of Alzheimer's Disease
Administration of Momordica charantia Enhances the Neuroprotection and Reduces the Side Effects of LiCl in the Treatment of Alzheimer's Disease
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DOI：
10.3390/nu10121888
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发表时间：
2018-12-01
期刊：
影响因子：
5.9
通讯作者：
Hsieh-Li, Hsiu Mei
中科院分区：
文献类型：
--
作者：
Huang, Hei-Jen;Chen, Shu-Ling;Hsieh-Li, Hsiu Mei
最近，使用天然食品补充剂来减少用于治疗各种疾病的化合物的副作用已经变得流行。氯化锂（LiCl）对神经系统疾病有一定的保护作用，包括阿尔茨海默病（AD）。然而，其对各种系统的毒性作用以及与其他药物的一些相关相互作用限制了其在临床实践中的广泛应用。本研究探讨了氯化锂与苦瓜（MC）联合治疗AD的体内外药理作用。体外实验结果表明，在高血糖或tau蛋白过度磷酸化的情况下，神经保护作用的顺序为MC 5、MC 3、MC 2和MC 5523。因此，将MC 5523（80 mg/kg;经口管饲）和/或LiCl（141.3 mg/kg;腹膜内注射）应用于接受脑室内注射链脲佐菌素（icv-STZ，3 mg/kg）28天的卵巢切除（OVX）的3xTg-AD雌性和C57 BL/6 J（B6）雄性小鼠。我们发现，联合治疗不仅通过减少肝毒性增加了存活率，而且还增加了icv-STZ OVX 3xTg-AD小鼠中与抗神经胶质增生相关的神经保护作用。此外，MC 5523和LiCl的共同治疗预防了与icv-STZ B6小鼠中减少的神经元损失、神经胶质增生、寡聚体A水平和tau过度磷酸化相关的记忆缺陷，并增加了突触相关蛋白和pS 9-GSK 3（失活形式）的表达水平。因此，MC 5523联合LiCl可能是治疗AD的潜在策略。
Recently, the use of natural food supplements to reduce the side effects of chemical compounds used for the treatment of various diseases has become popular. Lithium chloride (LiCl) has some protective effects in neurological diseases, including Alzheimer's disease (AD). However, its toxic effects on various systems and some relevant interactions with other drugs limit its broader use in clinical practice. In this study, we investigated the in vitro and in vivo pharmacological functions of LiCl combined with Momordica charantia (MC) in the treatment of AD. The in vitro results show that the order of the neuroprotective effect is MC5, MC3, MC2, and MC5523 under hyperglycemia or tau hyperphosphorylation. Therefore, MC5523 (80 mg/kg; oral gavage) and/or LiCl (141.3 mg/kg; intraperitoneal injection) were applied to ovariectomized (OVX) 3xTg-AD female and C57BL/6J (B6) male mice that received intracerebroventricular injections of streptozotocin (icv-STZ, 3 mg/kg) for 28 days. We found that the combined treatment not only increased the survival rate by reducing hepatotoxicity but also increased neuroprotection associated with anti-gliosis in the icv-STZ OVX 3xTg-AD mice. Furthermore, the cotreatment with MC5523 and LiCl prevented memory deficits associated with reduced neuronal loss, gliosis, oligomeric A level, and tau hyperphosphorylation and increased the expression levels of synaptic-related protein and pS9-GSK3 (inactive form) in the icv-STZ B6 mice. Therefore, MC5523 combined with LiCl could be a potential strategy for the treatment of AD.