Quercetin attenuates AZT-induced neuroinflammation in the CNS

• Published in: Scientific reports Vol. 8; no. 1; pp. 6194 - 8
• Main Authors: Yang, Yi, Liu, Xiaokang, Wu, Ting, Zhang, Wenping, Shu, Jianhong, He, Yulong, Tang, Shao-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.04.2018; Nature Publishing Group
• Subjects: 13/1; 13/51; 14; 631/378/1697; 631/378/371; Animals; Anti-HIV Agents - adverse effects; Antioxidants; Antioxidants - pharmacology; Antiretroviral drugs; Astrocytes - metabolism; Central nervous system; Central Nervous System Diseases - drug therapy; Central Nervous System Diseases - etiology; Central Nervous System Diseases - metabolism; Central Nervous System Diseases - pathology; Chronic exposure; Cytokines; Cytokines - metabolism; Disease Models, Animal; Flavones; Highly active antiretroviral therapy; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Inflammation; Mice; multidisciplinary; Neurotoxicity; Nucleoside reverse transcriptase inhibitors; Protease inhibitors; Quercetin; Quercetin - pharmacology; RNA-directed DNA polymerase; Science; Science (multidisciplinary); Spinal cord; Wnt protein; Wnt-5a Protein - metabolism; Zidovudine; Zidovudine - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24618-2

Highly active anti-retroviral therapy (HAART) is very effective in suppressing HIV-1 replication in patients. However, continuous HAART is required to prevent viral rebound, which may have detrimental effects in various tissues, including persistent neuroinflammation in the central nervous system (CNS). Here, we show that quercetin (3,5,7,3’,4’-pentahydroxy flavones), a natural antioxidant used in Chinese traditional medicines, suppresses the neuroinflammation that is induced by chronic exposure to Zidovudine (azidothymidine, AZT), a nucleoside reverse transcriptase inhibitor (NRTI) that is commonly part of HAART regimens. We found that the up-regulation of pro-inflammatory cytokines and microglial and astrocytic markers induced by AZT (100 mg/kg/day; 8 days) was significantly inhibited by co-administration of quercetin (50 mg/kg/day) in the mouse cortex, hippocampus and spinal cord. We further showed that quercetin attenuated AZT-induced up-regulation of Wnt5a, a key regulator of neuroinflammation. These results suggest that quercetin has an inhibitory effect on AZT-induced neuroinflammation in the CNS, and Wnt5a signaling may play an important role in this process. Our results may further our understanding of the mechanisms of HAART-related neurotoxicity and help in the development of effective adjuvant therapy.