Palmatine attenuates LPS-induced neuroinflammation through the PI3K/Akt/NF-κB pathway.

To investigate the key molecular mechanisms of palmatine for the treatment of neuroinflammation through modulation of a pathway using molecular docking, molecular dynamics (MD) simulation combined with network pharmacology, and animal experiments. Five alkaloid components were obtained from the traditional Chinese medicine Huangteng through literature mining. Molecular docking and MD simulation with acetylcholinesterase were used to screen palmatine. At the animal level, mice were injected with LPS intracerebrally to cause a neuroinflammatory model, and the Morris water maze experiment was performed to examine the learning memory of mice. Anxiety levels were tested using the autonomous activity behavior experiment with the open field and elevated behavior experiments. HE staining and Niss staining were performed on brain tissue sections to observe morphological lesions and apoptosis; serum was examined for inflammatory factors TNF-α, IL-6, and IL-1ß; Western blot was performed to detect the protein expression. The expression of PI3K/AKT/NFkB signaling pathway-related proteins was examined by Western blot. The results of network pharmacology showed that the screening of palmatine activation containing the PI3K/Akt/NFkB signaling pathway exerts antineuroinflammatory effects. Results from behavioral experiments showed that Pal enhanced learning memory in model mice, improved anxiety behavior, and significantly improved brain damage caused by neuroinflammation. The results of HE staining and Niss staining of brain tissue sections showed that palmatine could alleviate morphological lesions and nucleus damage in brain tissue. Palmatine improved the levels of serum inflammatory factors TNF-α, IL-6, and IL-1ß. SOD, MDA, CAT, ACH, and ACHE in the hippocampus were improved. Western blot results showed that palmatine administration ameliorated LPS-induced neuroinflammation through the PI3K/Akt/NFkB pathway.

Effect of glucosinolates on improvement of cognitive impairment in APP/PS1 double transgenic mice by regulating AKT/NFkB pathway / 中国药理学通报

Aim To investigate the effects of acteoside (AS) on BRAIN AKT and NFkB in APP/PS1 double transgenic mice. Methods Fifty healthy APP/PS1 transgenic mice, half male and half female, and 10 control C57 mice were given the drug by gavage for 60 consecutive days. During the period of administration, and new object recognition experiments were conducted to detect the expression of AKT and NFkB related proteins in the hippocampus and cortex of the mice. Results Compared with model group, AS could significantly improve the nesting behavior of mice and en- hance the interest of exploring new objects in mice with Alzheimer' s disease. At the same time, compared with model group, AS significantly reduced the ratio of NFkB p-p65 /NFkB p65 in hippocampus and cortical tissues, and increased the ratio of p-AKT-308 /AKT and p-AKT473 /AKT. Conclusions AS may inhibit the apoptosis of nerve cells and protect nerve cells through the regulation of AKT and NFkB to treat neurodegenerative diseases.