Desoxyrhapontigenin attenuates neuronal apoptosis in an isoflurane-induced neuronal injury model by modulating the TLR-4/cyclin B1/Sirt-1 pathway

Feng Liang,Xin Fu,Yunpengfei Li,Fanglei Han

doi:10.1186/s13568-020-01105-4

Abstract

This study investigated the protective effect of desoxyrhapontigenin (DOP) against isoflurane (ISF)-induced neuronal injury in rats. Neuronal injury was induced in pups by exposing them to 0.75% ISF on postnatal day 7 with 30% oxygen for 6 h. The pups were treated with DOP 10 mg/kg, i.p., for 21 days after ISF exposure. The protective effect of DOP was estimated by assessing cognitive function using the neurological score and the Morris water maze. Neuronal apoptosis was assessed in the hippocampus using the TUNEL assay, and protein expression of caspase-3, Bax, and Bcl-2 was measured by Western blotting. The levels of cytokines and oxidative stress parameters were assessed by ELISA. Western blotting and RT-PCR were performed to measure the expression of NF-kB, TLR-4, Sirt-1, and cyclin B1 protein in the brain. The cognitive function and neurological function scores were improved in the DOP group compared with the ISF group. Moreover, DOP treatment reduced the number of TUNEL-positive cells and the expression of caspase-3, Bax, and Bcl-2 protein in the brains of rats with neuronal injury. The levels of mediators of inflammation and oxidative stress were reduced in the brain tissue of the DOP group. Treatment with DOP attenuated the protein expression of TLR-4, NF-kB, cyclin B1, and Sirt-1 in the brain tissue of rats with neuronal injury. In conclusion, DOP ameliorates neuronal apoptosis and improves cognitive function in rats with ISF-induced neuronal injury. Moreover, DOP treatment can prevent neuronal injury by regulating the TLR-4/cyclin B1/Sirt-1 pathway.

Highlights

Anaesthetics are used to relieve pain to enable surgery and medical procedures (Lee 2017)
DOP alleviates ISF‐induced neuronal apoptosis Figure 3 shows the effect of DOP on neuronal apoptosis, based on the number of TUNEL-positive cells and protein expression of caspase-2, Bcl-2, and Bax in brain tissues with neuronal injury
Anaesthetics like isoflurane are commonly used for the image studies and surgical procedure including in children (Bodolea 2016)

Summary

Introduction

Anaesthetics are used to relieve pain to enable surgery and medical procedures (Lee 2017). Anaesthetics affect learning and memory in the developing brain by inducing neuronal apoptosis (Wu et al 2019). ISF exposure enhanced the expression of caspase-3 and deposition of β-amyloid peptide (Aβ), which contribute to the apoptotic pathway (Jiang and Jiang 2015). Glial cells play a central role in this response, which is mediated by the TLR-4 pathway and apoptosis-associated factors, such as p53 and NF-kB (Lei et al 2019). In cerebral ischemia, the TLR-4 pathway is regulated by NF-kB, and a reduction in TLR-4 expression decreases inflammation in ischemic stroke (Ou et al 2014). Activation of TLR-4 downregulates Sirt-1 expression in neuronal injury (Pucci et al 2000). Cyclin B1 is downregulated in inflamed tissues, which further contributes to the activation of apoptosis (Venkatesan et al 2016)

Methods

Results

Conclusion