Pterostilbene inhibits amyloid‐β‐induced neuroinflammation in a microglia cell line by inactivating the NLRP3/caspase‐1 inflammasome pathway

Abstract

Neuroinflammation has been known as an important pathogenetic contributor of Alzheimer's disease (AD). Pterostilbene is a natural compound which has neuroprotective activity. However, the effect of pterostilbene on amyloid-β (Aβ)-induced neuroinflammation has not been clarified. The aim of the present study was to investigate the effect of pterostilbene on Aβ-induced neuroinflammation in microglia. The results indicated that pterostilbene attenuated Aβ -induced cytotoxicity of BV-2 cells. Aβ induced NO production and iNOS mRNA and protein expression, while pterostilbene inhibited the induction. The expression and secretion levels of IL-6, IL-1β, and TNF-α were enhanced by Aβ treatment, whereas pterostilbene decreased them. Aβ activated NLRP3/caspase-1 inflammasome, which was inactivated by pterostilbene. In addition, the inhibitor of caspase-1 Z-YVAD-FMK attenuated the Aβ -induced neuroinflammation in BV-2 cells. In conclusion, pterostilbene attenuated the neuroinflammatory response induced by Aβ in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

“…Recently, accumulating evidences have demonstrated the benefits of PTE and other analogue stilbenoids, including resveratrol, piceatannol, and gnetol, against inflammatory and oxidative processes in vitro and in vivo [ 9 ]. The anti-inflammatory effects of PTE involve many intra- and extracellular signals, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), NLRP3, NF- κ B, TNF- α , and ILs [ 26 – 28 , 42 , 43 ]. We previously reported that PTE alleviates early inflammatory injury after SAH by inhibiting NLRP3 inflammasome and Nox2-related oxidative stress [ 24 ] and also attenuates the secondary astrocyte-induced inflammatory and oxidative stress after ischemia reperfusion injury by suppressing NF- κ B signalling [ 18 ].…”

“…Previously, we have found that PTE attenuates neural impairments in different neurological disorders, including glutamate or high-glucose-induced oxidative stress in neural cells [ 19 , 20 ], inflammation and mitochondrial oxidative stress injury after cerebral ischemia reperfusion [ 18 , 25 ], inflammation and oxidation-involved early brain injury following subarachnoid haemorrhage (SAH) [ 24 ]. Additionally, recent studies have shown that PTE inhibits the amyloid- β - and lipopolysaccharide- (LPS-) induced activation of microglia [ 26 – 28 ], whereas, it remains not fully clear whether PTE exerts neuronal protective effects by regulating microglia-mediated inflammatory and oxidative injury, as well as the molecular mechanisms.…”

Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders

“…It is important to note that pterostilbene exhibited higher oral availability than that from resveratrol due to its two methoxy groups . In the BV2 microglia cells, pterostilbene increased cell viability and alleviated inflammation through suppressing expression of proinflammatory cytokines, NLRP3 and caspase‐1 . Treatment with z‐YVAD‐fmk as a caspase‐1 inhibitor has confirmed that pterostilbene alleviated neuroinflammation in BV‐2 microglial cells due, at least in part, to regulation of the NLRP3/caspase‐l/IL‐1β axis.…”

Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease

“…In a model of Aβ (Aβ1-42)-induced neuroinflammation in BV-2 murine microglial cells, pterostilbene decreases the expression and levels of NO and proinflammatory cytokines (IL-6, IL-1β, and TNF-α). Furthermore, pterostilbene was able to inhibit the inflammasome NLRP3/caspase-1 (CASP1) pathway, being a promising agent for the treatment of AD (Li et al, 2018). Pterostilbene was more effective than RV in neuromodulating the deleterious effects of aging and AD.…”