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Clinically, high levels of acrolein (a highly reactive α, β-unsaturated aldehyde) and acrolein adducts are detected in the brain of patients with CNS neurodegenerative diseases, including Alzheimer's disease and spinal cord injury. Our previous study supports this notion by showing acrolein as a neurotoxin in a Parkinsonian animal model. In the present study, the effect of AZD6244 (an ATP non-competitive MEK1/2 inhibitor) on acrolein-induced neuroinflammation was investigated using BV-2 cells and primary cultured microglia. Our immunostaining study showed that lipopolysaccharide (LPS, an inflammation inducer as a positive control) increased co-localized immunoreactivities of phosphorylated ERK and ED-1 (a biomarker of activated microglia) in the treated BV-2 cells. Similar elevation in co-localized immunoreactivities of phosphorylated ERK and ED-1 was detected in the acrolein-treated BV-2 cells. Furthermore, Western blot assay showed increases in phosphorylated ERK in BV-2 cells subjected to LPS (1 μg/mL) or acrolein (30 μM); these increases were blocked by AZD6244 (10 μM). At the same time, AZD6244 attenuated LPS-induced TNF-α (a pro-inflammatory cytokine) and cyclooxygenase-II (COX II, a pro-inflammatory enzyme). Consistently, AZD6244 reduced acrolein-induced elevations in COX-II mRNA and COX-II protein expression. In addition, AZD6244 inhibited acrolein-induced increases in activated caspase 1 (a biomarker of inflammasome activation) and heme oxygenase-1 (a redox-regulated chaperone protein) in BV-2 cells. Using a transwell migration assay, AZD6244 attenuated acrolein (5 μM)-induced migration of BV-2 cells and primary cultured microglia. In conclusion, our study shows that acrolein is capable of inducing neuroinflammation which involved ERK activation in microglia. Furthermore, AZD6244 is capable of inhibiting acrolein-induced neuroinflammation. Our study suggests that ERK inhibition may be a neuroprotective target against acrolein-induced neuroinflammation in the CNS neurodegenerative diseases.
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http://dx.doi.org/10.1007/s12035-019-01758-8 | DOI Listing |
Eur J Med Chem
December 2024
Shaanxi Key Laboratory of Natural Products & Chemical Biology, Shaanxi Engineering Center of Bioresource Chemistry & Sustainable Utilization, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, PR China. Electronic address:
Eleven new chromane meroterpenoids (1-11), along with 24 known ones (12-35) were isolated from Rhododendron capitatum, a Tibetan medicine. Their structures were determined via extensive spectroscopic methods. The absolute configurations of 1 and 2 were determined by comparison of the experimental and theoretically calculated ECD data.
View Article and Find Full Text PDFPhytochemistry
December 2024
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, PR China; Natural Products Research Center of Guizhou Province, Guiyang, 550014, PR China. Electronic address:
Six previously undescribed sesquiterpenes, magnogranoides A-F (1-6), along with 10 known terpenes, were isolated from the leaves of Magnolia grandiflora L. Six previously undescribed sesquiterpene derivatives (11a-11e and 14a) were synthesized using chemical methods. Those structures were identified through extensive spectroscopic data and quantum chemical calculations.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
September 2024
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
This study aims to investigate the effect of essential oil of Acori Tatarinowii Rhizoma on microglial pyroptosis and decipher the underlying mechanism. BV-2 cells were treated with 1 μg·mL~(-1) lipopolysaccharide(LPS) and 10 μmol·L~(-1) nigericin sodium salt for the modeling of pyroptosis. The cells were treated with different doses of essential oil of Acori Tatarinowii Rhizoma, and then the cell viability and apoptosis were examined by the CCK-8 assay and flow cytometry, respectively.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Key Laboratory of Green Chemical Media and Reactions (Ministry of Education), Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, PR China. Electronic address:
Given the promising anti-inflammatory activity of the HIV integrase inhibitor dolutegravir and the widespread use of the 1,2,3-triazole structure in anti-inflammatory drug development, this study aimed to enhance dolutegravir's efficacy by introducing a 1,2,3-triazole group. As a result, four series of dolutegravir derivatives were synthesized. Screening these derivatives for anti-inflammatory activity in microglial cells revealed that compound 6k demonstrated the most potent anti-inflammatory effect without significant cytotoxicity.
View Article and Find Full Text PDFMolecules
November 2024
Department of Korean Medicine, College of Korean Medicine, Semyung University, Jecheon 27136, Republic of Korea.
Hedl. is a traditional medicinal plant in Korea, China, and Japan with known antioxidative, anti-inflammatory, anti-atherogenic, and anti-melanin activities. However, its anti-neuroinflammatory effects remain largely unknown.
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