Abstract
Neuroinflammation is a major cause of central nervous system (CNS) damage and can result in long-term disability and mortality. Therefore, the development of effective anti-neuroinflammatory agents for neuroprotection is vital. To our surprise, the naturally occurring molecule alantolactone (Ala) was reported to significantly inhibit tumor growth and metastasis as a result of its excellent anti-inflammatory effects. Thus, we proposed that it could also act as an anti-neuroinflammatory agent. Thus, in this study, a coculture system of BV2 cells and PC12 cells were used as an in vitro neuroinflammatory model to investigate the anti-neuroinflammatory mechanism of Ala. The results indicated that Ala downregulated the expression of proinflammatory factors by suppressing the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.
Highlights
Central nervous system (CNS) damage, including that caused by stroke, traumatic brain injury, and neurodegenerative disease, is the most prevalent cause of long-term disability and death [1,2].A growing body of research has suggested that neuroinflammation is a major mechanism of CNS damage [3]
100 ng/mL of LPS induced the development of ameboid BV2 cells, but the morphological change was partially suppressed by Ala pretreatment (Figure 1B)
The result of the keyFluor488-EdU kit assay suggested that LPS activated the BV2 cells and improved cell proliferation, but this was weakened by Ala treatment of the culture
Summary
A growing body of research has suggested that neuroinflammation is a major mechanism of CNS damage [3]. Currently available agents that target neuroinflammation have failed to achieve significant clinical results in the amelioration of CNS injury [4]. The neuroinflammation mechanism is initiated by a large number of proinflammatory factors that are produced by immune effector cells derived from brain tissue [7,8]. The activation of Toll-like receptors in immune effector cells causes the upregulated expression and release of proinflammatory factors in neighboring cells, leading to the cascading amplification of inflammation, which results in neuroinflammation [9]. Decreasing the production and release of proinflammatory factors is an effective way to inhibit neuroinflammation.
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