Huang Hong, Zhang Yiwen, Yao Caihong, He Qinghu, Chen Fang, Yu Han, Lu Guanghua, Jiang Ning, Liu Xinmin
Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Sino-Pakistan Center on Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, China.
Front Pharmacol. 2022 Aug 29;13:890330. doi: 10.3389/fphar.2022.890330. eCollection 2022.
Chronic restraint stress (CRS) is a classic animal model of stress that can lead to various physiological and psychological dysfunctions, including systemic neuroinflammation and memory deficits. Fresh Blume (FG), the unprocessed raw tuber of Blume, has been reported to alleviate the symptoms of headache, convulsions, and neurodegenerative diseases, while the protective effects of FG on CRS-induced cognitive deficits remain unclear. This work aimed to evaluate the effects of FG on CRS-induced cognitive deficits through multiplex animal behavior tests and to further explore the related mechanism by observing the expression of mitochondrial apoptosis-related proteins in the mouse hippocampus. In experiments, mice were subjected to the object location recognition test (OLRT), new object recognition test (NORT), Morris water maze test (MWMT), and passive avoidance test (PAT) to evaluate the learning and memory ability. In experiments, the expression of the AKT/CREB pathway, the fission- and apoptosis-related proteins (Drp1, Cyt C, and BAX), and the proinflammatory cytokines' (TNF-α and IL-1β) level in the hippocampus was examined. Our results demonstrated that in spontaneous behavior experiments, FG significantly improved the cognitive performance of CRS model mice in OLRT ( < 0.05) and NORT ( < 0.05). In punitive behavior experiments, FG shortened the escape latency in long-term spatial memory test (MWMT, < 0.01) and prolonged the latency into the dark chamber in non-spatial memory test (PAT, < 0.01). Biochemical analysis showed that FG treatment significantly suppressed CRS-induced Cyt C, Drp1, and BAX activation ( < 0.001, < 0.01 and < 0.05), promoted the CREB, p-CREB, AKT, and p-AKT level ( < 0.05, < 0.01 and < 0.001), and inhibited the CRS-induced proinflammatory cytokines (TNF-α and IL-1β, < 0.05 and < 0.001) level in the hippocampus. Taken together, these results suggested that FG could attenuate cognitive deficits induced by CRS on multiple learning and memory behavioral tests.
慢性束缚应激（CRS）是一种经典的应激动物模型，可导致各种生理和心理功能障碍，包括全身神经炎症和记忆缺陷。新鲜的白附子（FG），即未加工的白附子生块茎，据报道可缓解头痛、惊厥和神经退行性疾病的症状，而FG对CRS诱导的认知缺陷的保护作用尚不清楚。这项工作旨在通过多种动物行为测试评估FG对CRS诱导的认知缺陷的影响，并通过观察小鼠海马中线粒体凋亡相关蛋白的表达进一步探索相关机制。在实验中，对小鼠进行物体位置识别测试（OLRT）、新物体识别测试（NORT）、莫里斯水迷宫测试（MWMT）和被动回避测试（PAT）以评估学习和记忆能力。在实验中，检测海马中AKT/CREB通路、裂变和凋亡相关蛋白（Drp1、细胞色素C和BAX）的表达以及促炎细胞因子（TNF-α和IL-1β）的水平。我们的结果表明，在自发行为实验中，FG显著改善了CRS模型小鼠在OLRT（<0.05）和NORT（<0.05）中的认知表现。在惩罚行为实验中，FG缩短了长期空间记忆测试（MWMT，<0.01）中的逃避潜伏期，并延长了非空间记忆测试（PAT，<0.01）中进入暗室的潜伏期。生化分析表明，FG处理显著抑制了CRS诱导的细胞色素C、Drp1和BAX激活（<0.001、<0.01和<0.05），促进了CREB、p-CREB、AKT和p-AKT水平（<0.05、<0.01和<0.001），并抑制了CRS诱导的海马中促炎细胞因子（TNF-α和IL-1β，<0.05和<0.001）水平。综上所述，这些结果表明FG可以在多种学习和记忆行为测试中减轻CRS诱导的认知缺陷。
