Tanshinone IIA Rescued the Impairments of Primary Hippocampal Neurons Induced by BV2 Microglial Over-Activation

Abstract

Activated microglia plays an important role in monitoring the microenvironment and prune neural process in healthy neural tissue, in order to maintain synaptic homeostasis. However, hyperactive microglia may release various cytotoxic factors and induce neuroinflammation, which cause neuronal damages leading to neurodegenerative diseases. Tanshinone IIA (TSA), an extract from traditional Chinese medicine, features potent anti-apoptotic and anti-inflammatory effects both in vitro and in vivo. But little is known on the effects of TSA on microglial-over-activation-induced neural impairments. In this study, by employing murine BV2 cell lines as well as the combinations of ELISA assay, immunostaining, western blotting analysis and RT-PCR, we found that TSA has the potential to exhibit anti-inflammatory effects. We hereby demonstrated that TSA rescued neural growth and development in the primary cultured hippocampal neurons from impairments caused by BV2 microglial over-activation insult. The results show that TSA attenuated the BV2 cell activation by lipopolysaccharide (LPS) stimulation through suppressing the NF-кB signal pathway. Also, conditioned mediums (CM) from TSA treated and activated BV2 cells protected against LPS-CM-induced neuronal death. Furthermore, TSA treatment could recover the inhibitory effects of LPS-CM on growth cone extension, neurite sprouting and outgrowth, as well as spinogenesis. Our findings support that TSA is capable of inhibiting BV2 cell over-activation thus has potential protective effects in the cultured hippocampal neurons. This study may lay a foundation for using TSA to restore cerebral injuries after severe neuroinflammation.

Tanshinone IIA protects motor neuron-like NSC-34 cells against lipopolysaccharide-induced cell injury by the regulation of the lncRNA TCTN2/miR-125a-5p/DUSP1 axis

“…Here, we used a motor neuron-like NSC-34 cell line induced by LPS to mimic the in vitro SCI cell model [ 21 ]. Our results validated that TSIIA protected NSC-34 cells against LPS-induced cell damage, in line with recent work [ 22 , 23 ]. Importantly, we provided a novel molecular explanation for the protective role of TSIIA in LPS-evoked cytotoxicity in NSC-34 cells.…”

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice

“…Sole albendazole treatment and albendazole combined with dexamethasone treatment increased the ganglion cell number slightly, whereas CPT or TSII-A combined with albendazole treatment were shown to help almost regain the initial number of ganglion cells, and the latter was more effective, indicating that albendazole combined with TSII-A can rescue the loss of ganglion cells caused by A. cantonensis infection significantly. Previous studies showed TSII-A played a vital role in protecting neurons such as dopaminergic neurons and hippocampal neurons [ 19 , 20 ], and may inhibit thebeta-amyloid-induced toxicity in rat cortical neurons [ 21 , 22 ]. In addition, TSII-A also has a protective effect on the cranial nerves when administered during the initial stages of cerebral ischemia [ 14 ].…”

miR-146a alleviates the apoptosis of hippocampal neurons induced by microglia activation via targeting TRAF6

“…1 Activated microglia is of great significance to monitor the microenvironment, clean up the damaged nerves, and prune neural process in healthy central nervous system so as to maintain synaptic homeostasis. 2 However, the continuously over-activated or out of control microglia may induce the release of many cytotoxic factors and lead to some inflammations, which can worsen neuronal damages, thereby resulting in neurodegenerative diseases. 3 Microglia cells are found to be activated and proliferated locally in the pathological process of central nervous system injury, inflammation, depression, Alzheimer's disease, and even epilepsy.…”