Depression is one of the most common neuropsychiatric disorders that is characterized by low mood, lack of motivation, slow thinking, and recurrent suicidal thoughts. The mechanism of action of palmatine in depression has been rarely reported and remains unclear. The present study examined the neuroprotective effects of palmatine on lipopolysaccharide (LPS)-induced oxidative stress, apoptosis, and depression-like behavior. In this study, cell apoptosis was evaluated by CCK-8, flow cytometry, and Hoechst 33258 staining in LPS-induced HT-22 cells. Meanwhile, reactive oxygen species (ROS) and mitochondrial membrane potential were detected in vitro. In vivo, we investigated depressive-like behaviors in mice by an open field test (OFT) and elevated plus-maze test (EPM). Additionally, the levels of superoxide dismutases (SOD), TNF-α, IL-1β, and IL-6 were detected by enzyme-linked immunosorbent assay. The hematoxylin-eosin staining and TUNEL staining were used to evaluate the pathology of the hippocampus. The expression of Nrf2/HO-1 and BAX/Bcl-2 pathways in the hippocampus were assessed by Western blot analysis. Palmatine could significantly reduce apoptosis and ROS levels, and improve mitochondrial damage. Moreover, palmatine significantly improves movement time and central square crossing time in OFT, and improves open arms and movement time in EMP. And the levels of SOD, TNF-α, IL-1β, and IL-6 were significantly decreased after palmatine treatment. More importantly, palmatine improved neuronal apoptosis in the hippocampus, and depression through BAX/Bcl-2 and Nrf2/HO-1 signaling pathways. We provide evidence that palmatine further alleviates the depressive-like behavior of LPS-induced by improving apoptosis and oxidative stress.

中文翻译：

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Palmatine 通过调节细胞凋亡和氧化应激改善 LPS 诱导的 HT-22 细胞和小鼠抑郁模型

抑郁症是最常见的神经精神疾病之一，其特征是情绪低落、缺乏动力、思维迟钝和反复出现自杀念头。palmatine 在抑郁症中的作用机制鲜有报道，仍不清楚。本研究检测了巴马汀对脂多糖 (LPS) 诱导的氧化应激、细胞凋亡和抑郁样行为的神经保护作用。在本研究中，通过 LPS 诱导的 HT-22 细胞中的 CCK-8、流式细胞术和 Hoechst 33258 染色评估细胞凋亡。同时，体外检测活性氧（ROS）和线粒体膜电位。在体内，我们通过旷场试验 (OFT) 和高架十字迷宫试验 (EPM) 研究了小鼠的抑郁样行为。此外，超氧化物歧化酶 (SOD)、TNF-α、IL-1β、酶联免疫吸附试验检测IL-6和IL-6。苏木精-伊红染色和TUNEL染色用于评估海马的病理学。通过蛋白质印迹分析评估海马中 Nrf2/HO-1 和 BAX/Bcl-2 通路的表达。Palmatine 可显着降低细胞凋亡和 ROS 水平，改善线粒体损伤。此外，palmatine 显着改善了 OFT 中的运动时间和中心方块交叉时间，并改善了 EMP 中的张开双臂和运动时间。并且 palmatine 处理后 SOD、TNF-α、IL-1β 和 IL-6 的水平显着降低。更重要的是，palmatine 通过 BAX/Bcl-2 和 Nrf2/HO-1 信号通路改善海马神经元凋亡和抑郁症。