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

Autor: Zeng J; Department of Agriculture and Rural Affairs of Jilin Province Pharmacy and Pharmaceutical Science and Technology, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China., Pei H; Department of Agriculture and Rural Affairs of Jilin Province Pharmacy and Pharmaceutical Science and Technology, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China., Wu H; Department of Agriculture and Rural Affairs of Jilin Province Pharmacy and Pharmaceutical Science and Technology, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China., Chen W; Department of Agriculture and Rural Affairs of Jilin Province Pharmacy and Pharmaceutical Science and Technology, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China., Du R; Department of Science and Technology of Jilin Province, Department of Traditional Chinese Medicine Industry in Xinjiang, Engineering Research Center for High-Efficiency Breeding and Product Development Technology of Sika Deer, Jilin, China., He Z; Department of Agriculture and Rural Affairs of Jilin Province Pharmacy and Pharmaceutical Science and Technology, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China.; Department of Science and Technology of Jilin Province, Department of Traditional Chinese Medicine Industry in Xinjiang, Engineering Research Center for High-Efficiency Breeding and Product Development Technology of Sika Deer, Jilin, China.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Jan; Vol. 38 (1), pp. e23544. Date of Electronic Publication: 2023 Oct 10.
DOI: 10.1002/jbt.23544
Abstrakt: 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-1β; 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-1β. 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.
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Databáze: MEDLINE
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