Baicalin mitigates cognitive impairment and protects neurons from microglia‐mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF‐κB signaling pathway

Abstract

Summary Aims Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti‐inflammation and neuroprotective properties; however, its effects during Alzheimer's disease ( AD ) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia‐induced neuroinflammation and to explore the mechanisms underlying its anti‐inflammation effects. Methods To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin‐1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation‐mediated neuron apoptosis in vivo and in vitro using Western blot, RT ‐ PCR , ELISA , immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti‐inflammation mechanisms underlying the effects of BAI , the protein expression of NLRP 3 inflammasomes and the expression of proteins involved in the TLR 4/ NF ‐κB signaling pathway were measured using Western blot and immunofluorescence. Results The results indicated that BAI treatment attenuated spatial memory dysfunction in APP / PS 1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation‐mediated neuron apoptosis, in APP / PS 1 mice and LPS (lipopolysaccharides)/Aβ‐stimulated BV 2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia‐induced neuroinflammation via suppression of the activation of NLRP 3 inflammasomes and the TLR 4/ NF ‐κB signaling pathway. Conclusion Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia‐mediated neuroinflammation during AD progression.

Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

“…11,50 Activated glial cells release inflammatory factors that contribute to subsequent neuroinflammation. 51 In our study, we found that NR administration reduced neuroinflammation and suppressed the activation of microglia and astrocytes by decreasing the expression of TNF-α in the brain. The antiinflammatory effect of NR may be related to its ability to protect BBB integrity.…”

“…BBB leakage leads to Ang ‐ entering the perivascular space, where Ang ‐ activates astrocytes and microglia by activating NFкB and signal transducer and activator of transcription protein 3 (STAT3) signaling . Activated glial cells release inflammatory factors that contribute to subsequent neuroinflammation . In our study, we found that NR administration reduced neuroinflammation and suppressed the activation of microglia and astrocytes by decreasing the expression of TNF‐α in the brain.…”

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

“…A wide range of therapeutic compounds (Table 3) have demonstrated their efficacy in animal models of AD-like pathologies, mainly by inhibiting TLR4 expression, suppressing microglial activation and pro-inflammatory cytokine levels, ameliorating learning and memory functions, inhibiting oxidative stress, and reducing apoptotic cell death and Aβ load (number and size of Aβ deposit) [120][121][122][123][124][125][126].…”

Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases

“…Spicatoside A, which is one of the active compounds of Liriope platyphylla, also possess anti-inflammatory and memory repairment in animal models of dementia [146]. Scutellaria baicalensis Georgi and Lindera neesiana extract have potential anti-inflammation and neuroprotective properties, and can be used during AD progression [120,147,148]. Broccoli extract enriched in sulforaphane attenuates neuroinflammation, and because of its neuroprotective role, it can be used for combating neurodegenerative diseases, such as AD, PD, MS, and ischemia [149].…”