Fatsia japonica extract exerts antioxidant and anti-neuroinflammatory effects on neuronal cells and a zebrafish model

Liu, Zhiming; Lee, Hwan; Dong, Linsha; Cheong, Sun Hee; Lee, Dong-Sung

doi:10.1016/j.jep.2024.117813

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…LPS challenge and the consequent ROS increase significantly reduced Nrf2 and HO-1 expression, which act as key regulators in the protection mechanisms against oxidative stress with a fundamental role in antioxidant metabolism and response, as well as in the modulation of neuroinflammation [58][59][60]. Both levosimendan and dobutamine treatment showed an enhancement of Nrf2 and HO-1 expression compared to LPS-challenged cells; these results were in accordance with previous papers that showed a significant increase in the Nrf2/HO-1 pathway following dobutamine or levosimendan treatment in mice [14,61] and in rats [62].…”

Section: Discussionmentioning

confidence: 99%

Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling

Mannino,

Urzì Brancati,

Lauro

et al. 2024

Biomedicines

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Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system (CNS). Levosimendan, a cardioprotective inodilator, and dobutamine, a β1-adrenergic agonist, are commonly used for the treatment of hypovolemic shock, thanks to their anti-inflammatory and antioxidant effects. For this reason, we aimed at investigating levosimendan and dobutamine’s neuroprotective effects in an “in vitro” model of lipopolysaccharide (LPS)-induced neuroinflammation. Human microglial cells (HMC3) were challenged with LPS (0.1 µg/mL) to induce an inflammatory phenotype and then treated with levosimendan (10 µM) or dobutamine (50 µM) for 24 h. Levosimendan and dobutamine significantly reduced the ROS levels and markedly increased Nrf2 and HO-1 protein expression in LPS-challenged cells. Levosimendan and dobutamine also decreased p-NF-κB expression and turned off the NLRP3 inflammasome together with its downstream signals, caspase-1 and IL-1β. Moreover, a reduction in TNF-α and IL-6 expression and an increase in IL-10 levels in LPS-stimulated HMC3 cells was observed following treatment. In conclusion, levosimendan and dobutamine attenuated LPS-induced neuroinflammation through NF-κB pathway inhibition and NLRP3 inflammasome activation via Nrf2/HO-1 signalling, suggesting that these drugs could represent a promising therapeutic approach for the treatment of neuroinflammation consequent to hypovolemic shock.

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