Objective The key molecular mechanism of palmatine in the treatment of Alzheimer's disease (AD) was investigated in this article. Methods Network pharmacology techniques constructed drug‐target‐disease relationship networks and predictive pathways of action. At the cellular level, lipopolysaccharide (LPS) was used to induce Raw 264.7 cells to establish an inflammation model, and interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF)‐α indicators were examined. Apoptosis was detected using Hoechst 33258. At the animal level, LPS was used to induce AD animal model, and behavioral performance were examined by water maze, and serum biochemical indexes were measured by ELISA. And the expression of PI3K and P‐AKT was observed by immunohistochemistry. Finally, molecular level validation was performed using the molecular docking technique. Results The result of Network pharmacological was predicted that palmatine may treat AD mainly through the PI3K pathway. Palmatine has no significant effect on Raw264.7 cells viability within 0.05 mg/ml, Palmatine can significantly induce Raw264.7 cells to secret IL‐6 and IL1‐β in a concentration‐dependent manner, but it has not obvious impact on NO and TNF‐α. Palmatine has a significant restorative effect on the cell viability of Raw264.7 in a concentration of 0.1 mg/ml. Palmatine can be concentration‐dependent to downregulate the secretion of LPS‐induced IL‐6. At the same time, Palmatine also has a significant effect on the level of TNF‐α induced by LPS, it also can slightly downregulate the secretion of IL‐1β. The results of Hoechst33258 showed that cells in the 0.025 mg/ml and 0.5 mg/ml delivery groups increased with different degrees of bright blue fluorescence, and apoptosis rate decreased. Animal experiments showed that palmatine effectively improved the learning and memory ability of AD mice. The immunohistochemical results exhibited that the expression of PI3K and P‐AKT in the model group decreased, but they were obvious reversed by palmatine The molecular docking results showed that palmatine and key targets had good docking, among which the binding to ERBB2, CDC42, MDM2, and mTOR was the most likely. Conclusion Palmatine has neuroprotective effects. Palmatine could effectively ameliorate memory impairment in AD mice by promoting the PI3K‐AKT pathway. Molecular docking results showed that palmatine has a better binding ability with mTOR.

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.

Chlorpyrifos (CPF), as an extensively used organophosphorus pesticide, often remains on food surfaces or contaminates water sources. CPF can cause many toxic effects on human production and life. As an additional product of non-medicinal parts of ginseng, the pharmacological activity of ginseng stem and leaf total saponin (GSLS) has been verified and applied in recent years. This study aimed to evaluate the protective effect of GSLS on CPF-induced liver damage in mice. Experimental results in vivo demonstrate that GSLS can reduce the accumulation of oxidation product MDA by relieving CPF-induced liver function indicators in mice and enhancing the antioxidant enzyme SOD and CAT activities of mice. With the decrease in mRNA expression of BAX, NF-KB, and TIMP in liver tissues, the mRNA expression of Nrf-2, HO-1, and XIAP increased. GSLS can alleviate CPF-induced liver toxicity through anti-inflammatory, antioxidant, and anti-inflammatory. In vitro experiments have proved that GSLS can show the ability to scavenge DPPH free radicals and hydroxyl radicals. In addition, GSLS can alleviate chlorpyrifos-induced ROS accumulation in L02 cells, alleviating cytokinetic potential reduction. In summary, by fighting oxidative stress, GSLS can alleviate liver damage caused by CPF.

Chlorpyrifos (CPF) is a class of toxic compounds which has been widely used in agriculture that can cause multiorgan damage to the liver, kidneys, testes, and nervous system. Currently, most studies on ginseng have concentrated on the roots and rhizomes, and less research has been conducted on the above-ground parts. Our laboratory found that ginseng stem and leaf total saponin (GSLS) features strong antioxidant activity. In this experiment, we selected different concentrations of CPF to induce hippocampal neuronal cell injury model in mice, conducted a cell survival screening test, and also selected appropriate concentrations of CPF to induce brain injury model in mice. CCK-8, flow cytometry, Elisa, Hoechst 33258 staining, Annexin V-FITC/PI staining, HE staining, Morris water maze, and qRT-PCR were adopted for detecting the effects of GSLS treatment on CPFinduced cell viability, mitochondrial membrane potential, reactive oxygen species (ROS) levels, Ca 2+ concentration and GSLS treatment on CPF-induced brain injury and related signaling in mice, respectively. The effects of GSLS treatment on CPF-induced brain injury and the related signaling pathways in mice were examined. The results showed that GSLS at 60 μg/ml and 125 μg/ml concentrations elevated the viability of CPF-induced HT22 cells, increased mitochondrial membrane potential, depleted ROS, decreased Ca 2+ concentration, and decreased apoptosis rate. Meanwhile, GSLS treatment significantly reduced CPF-induced escape latency in mice, elevated the number of entries into the plateau and effective area, increased the effective area and target quadrant residence time, as well as improved the pathological damage of mouse hippocampal neurons. The results of mouse brain sections demonstrated that GSLS treatment significantly increased SOD and CAT activities and lowered MDA accumulation in CPF-induced mice. qRT-PCR revealed that PTEN mRNA expression was significantly decreased with PI3K and AKT expression being significantly increased in GSLS-treated CPF-induced mice. Thus, the obtained results indicate that GSLS can effectively antagonize CPF-induced brain toxicity in mice through regulating PTEN/PI3K/AKT pathway.www.aging-us.com AGINGaltered activity and impulsivity [7][8][9]. Up to the present, related studies have provided sufficient evidence to show that there exists a strong link between CPF exposure, long-term persistent cognitive impairment and increased risk of neurodegenerative diseases [10,11].

No abstract