Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease
Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease
复制标题
去孢子皮的灵芝孢子对链脲佐菌素诱导的散发性阿尔茨海默病大鼠模型的预防作用
DOI：
10.1016/j.jep.2020.113725
复制
发表时间：
2021
影响因子：
5.4
通讯作者：
Zhang Yong-He
中科院分区：
文献类型：
--
作者：
Zhao Hui-Ling;Cui Su-Ying;Qin Yu;Liu Yu-Tong;Cui Xiang-Yu;Hu Xiao;Kurban Nurhumar;Li Ming-Yan;Li Zhen-Hao;Xu Jing;Zhang Yong-He
灵芝的民族药理学意义。灵芝（lucidum, Lingzhi），也被称为“长生不老的蘑菇”，在亚洲被广泛用于改善健康和长寿，已有数千年的历史。基于其广泛的药理和治疗活性，灵芝及其孢子已被用于促进健康。该物种在中国传统方剂中被记录为益智药，并被认为可以改善阿尔茨海默病的认知功能障碍。然而，对g的促智作用及其分子机制了解甚少。lucidumspores。目的研究孢子囊缺陷灵芝（ganoderma lucidum孢子，RGLS）对学习记忆障碍的保护作用及其机制。材料与方法在Morris水迷宫中，采用脑室注射链脲佐菌素（STZ）诱导散发性阿尔茨海默病大鼠模型，观察RGLS对学习和记忆障碍的影响。Western blot检测海马组织中β淀粉样蛋白（Aβ）表达、Tau蛋白表达及磷酸化、脑源性神经营养因子（BDNF）及BDNF受体原肌球蛋白相关激酶B （TrkB）的变化。结果RGLS（360和720 mg/kg）可显著增强stz诱导的散发性阿尔茨海默病大鼠模型的记忆，逆转stz诱导的Aβ表达和Tau蛋白表达以及Ser199、Ser202和Ser396位点磷酸化的升高。stz诱导的神经营养因子减少，包括BDNF、TrkB和TrkB Tyr816位点磷酸化，通过RGLS治疗可以逆转。结论RGLS可抑制stz诱导的散发性阿尔茨海默病模型大鼠的学习和记忆障碍，其作用机制可能与RGLS降低海马中a β表达和Tau过度磷酸化以及BDNF-TrkB信号通路的调节有关。
Ethnopharmacological relevanceGanoderma lucidum(G. lucidum, Lingzhi), also known as “immortality mushroom” has been broadly used to improve health and longevity for thousands of years in Asia.G. lucidumand its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action ofG. lucidumspores.Aim of the studyThe present study investigated the protective effects of sporoderm-deficientGanoderma lucidumspores (RGLS) against learning and memory impairments and its mechanism of action.Materials and methodsIn the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid β (Aβ) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot.ResultsTreatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aβ expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS.ConclusionThese findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aβ expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.