Background
Central nervous system (CNS) injuries are a leading cause of permanent functional impairment in humans. Nerve damage can be aggravated by neuroinflammation mediated by protein complexes known as inflammasomes, such as the NLRP3 inflammasome which is a key mediator of caspase-1 and interleukin-1β (IL-1β) /interleukin-18 (IL-18) activation. Lycopus lucidus Turcz (LLT) is a traditional medicinal herb that exerts therapeutic effects against oxidative stress, inflammation, and angiogenesis; however, it remains unclear whether LLT can directly protect neurons against damage, and the underlying molecular mechanisms are poorly understood.
Methods
We investigated the neuroprotective effect of LLT against hydrogen peroxide (H2O2)-induced neuronal damage in cultured primary rat cortical neurons, as well as the potential underlying mechanisms. Neuronal viability and cell death assays were used to determine the effects of LLT on neuroprotection, while the mode of cell death was confirmed using flow cytometry. Changes in the expression of inflammatory factors involved in activation of the NLRP3 inflammasome were measured using immunocytochemistry (ICC) and confirmed by real-time PCR. And, we analyzed that the effect of LLT on neurotrophic factors secretion and synaptic connectivity using ICC in H2O2-induced neuron at 7 days in vitro.
Results
LLT effectively protected cultured rat cortical neurons from H2O2-induced injury by significantly inhibiting NLRP3 inflammasome activation. In addition, LLT significantly reduced caspase1 activation, which is known to be induced by inflammasome formation, and consequently regulated the secretion of IL-1β/IL-18. We demonstrated that LLT enhances axonal elongation and synaptic connectivity against H2O2-induced injury of rat primary cortical neuron.
Conclusions
Together, these results demonstrate that LLT can directly protect cultured cortical neurons from H2O2-induced neuronal damage by inhibiting NLRP3 inflammasome activation and the secretion of caspase-1 and IL-1β/IL-18. Thus, our study provides new insights into the therapeutic mechanisms of LLT and suggests that the NLRP3 inflammasome could be a promising target for treating neurological diseases.