Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

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.

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation

“…An obvious further direction of research into the activity of new compounds is the study involving immune cells, e.g., through the use of co-cultures of microglia and neuronal cells. The involvement of immune cells would additionally investigate the indirect effects of LPS on neuronal cells, primarily through the proinflammatory cytokines IL-1β and IL-6 [9].…”

“…From several studies, it is known that the proinflammatory effect of LPS on PC12 cells is based on activation of the TLR4 (Toll-like receptor 4). Activation of the TLR4 receptor induces NF-κB transcription factor, which promotes the expression of proinflammatory cytokines and chemokines [9,14,17,40]. The treatment of PC12 cells with LPS at a concentration of 1 mg/mL for 18 h resulted in an approximately six-fold increase in NF-κB compared to the control [20].…”

Hydroxysafflor Yellow A Together with Blood–Brain Barrier Regulator Lexiscan for Cerebral Ischemia Reperfusion Injury Treatment

“…For such CNS injury, the neurotrophic factor plays an important role in promoting the functional recovery and maintenance. 39 , 40 It has been reported that HSYA could increase the content of the BDNF protein and exert neuroprotective effects on cerebral ischemic injury. 41 As shown in Figure 10 , CIR resulted in the down-regulation of BDNF expression.…”

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Buyang Huanwu Decoction in the treatment of Ischemic Stroke

“…Besides, formononetin mediated neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway [67]. MAPK signaling pathways may be a therapeutic targets for stroke [68]. Researches showed that suppressing the NF-κB and MAPK signaling pathways would down regulate the expression of proin ammatory factors.…”

“…Researches showed that suppressing the NF-κB and MAPK signaling pathways would down regulate the expression of proin ammatory factors. MAPK pathways could be a promising candidate for future applications in CNS injury treatment [69]. BHD alleviated pressure overload induced cardiac remodeling by suppressing TGF-β/Smads and MAPKs signaling activated brosis [70].…”