Mogroside V Alleviates Lipopolysaccharide-Induced Neuroinflammation via Inhibition of TLR4-MyD88 and Activation of AKT/AMPK-Nrf2 Signaling Pathway

Abstract

As innate immune effector cells in the central nervous system (CNS), microglia not only are essential for the normal development of nervous system but also act on different neurological diseases, including Alzheimer’s disease (AD), Huntington's disease (HD), and other neuroinflammatory diseases. 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-α (TNF-α), interleukin-1β (IL-1β), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2 cells. 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′-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of γ-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.

Helicobacter pylori and Alzheimer’s Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention

“…A study indicated DL0410 ((1,1′-([1,1′-biphenyl]-4,4′-diyl)­bis­(3-(piperidin-1-yl)­propan-1-one)­dihydrochloride), a novel dual cholinesterase inhibitor, exerts neuroprotective effects against hippocampus and cortex injury and maintains the blood–brain barrier via mediating of the TLR4/Myd88 signaling pathway . Liu et al reported that mogroside V alleviated lipopolysaccharide-induced neuroinflammation through inhibition of the TLR4/Myd88 inflammation pathway . P53 was reported as the downstream gene of the TLR4/Myd88 inflammation pathway as the p53 expression increased after activation of TLR4/Myd88 signaling by LPS .…”

“…64 Liu et al reported that mogroside V alleviated lipopolysaccharide-induced neuroinflammation through inhibition of the TLR4/Myd88 inflammation pathway. 65 P53 was reported as the downstream gene of the TLR4/Myd88 inflammation pathway as the p53 expression increased after activation of TLR4/Myd88 signaling by LPS. 39 Our study is consistent with a previous report.…”

Mogroside V Alleviates Oocyte Meiotic Defects and Quality Deterioration in Benzo(a)pyrene-Exposed Mice

“…Mogroside V (MV) is the major component of mogrosides in the fruit of S. grosvenorii. In vitro studies have demonstrated that MV can alleviate lipopolysaccharide-induced inflammation in cultured cells (Li et al, 2019;Liu et al, 2021). Moreover, we found that MV supplementation in vitro maturation medium can promote porcine oocyte maturation (Nie et al, 2020), alleviate the quality deterioration of in vitro ageing oocytes (Nie et al, 2019), and protect porcine oocytes from meiotic defects induced by LPS (Yan et al, 2021).…”

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier

“…Lonicera japonica has been reported to effect the release of inflammatory factors ( tnf-α , il-1β , il-6 and ifn-γ ) through several signaling pathways, such as the IL-17 signaling pathway and the p38/MAPK signaling pathway [ 53 , 54 , 55 ]. According to some studies, Mogroside V is also able to reduce the expression of inflammatory factors such as il-1β , il -6 , and tnf-α , and to inhibit the activation of cox-2 [ 26 , 56 , 57 ]. Glucoraphanin can be transformed into the active substance sulforaphane under the action of human intestinal flora or myrosinase, and sulforaphane can further activate the Nrf2 signaling pathway of human cells to exert an anti-inflammatory effect [ 58 , 59 , 60 ].…”