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Mogroside V (Mog), a natural plant active ingredient and isolated form of Momordica grosvenori, has been shown to possess anti-inflammatory action, but few studies were carried out to investigate the effects of Mog on neuroinflammation. This study aimed to investigate the role of Mog in lipopolysaccharide- (LPS-) induced neuroinflammation and neuronal damage, revealing the underlying mechanisms. Our data indicated that Mog significantly inhibited the LPS-induced production of proinflammatory factors, such as tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2\u2009cells. We found that Mog also suppressed toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), the phosphorylation of mitogen-activated protein kinases (MAPKs), adenosine 5\u2032-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-\u03baB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of \u03b3-glutamyl cysteine synthetase catalytic subunit (GCLC), modifier subunit (GCLM), heme oxygenase-1 (HO-1), and quinine oxidoreductase 1 (NQO1) proteins, mostly depending on the nuclear translation of nuclear factor erythroid-2 related factor 2 (Nrf2). In contrast, pretreatment with inhibitors of AKT can suppress the phosphorylation of AMPK, Nrf2, and its downstream proteins expression. In summary, Mog might play a protective role against LPS-induced neurotoxicity by inhibiting the TLR4-MyD88 and activation of AMPK\/AKT-Nrf2 signaling pathway.<\/jats:p>","DOI":"10.1155\/2021\/5521519","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T23:05:24Z","timestamp":1619823924000},"page":"1-13","source":"Crossref","is-referenced-by-count":10,"title":["Mogroside V Alleviates Lipopolysaccharide-Induced Neuroinflammation via Inhibition of TLR4-MyD88 and Activation of AKT\/AMPK-Nrf2 Signaling Pathway"],"prefix":"10.1155","volume":"2021","author":[{"given":"Yuanyuan","family":"Liu","sequence":"first","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, 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