Solasonine ameliorates cerebral ischemia-reperfusion injury via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway

Solasonine (SS), the main active ingredient of Solanum nigrum L., has been reported to possess a variety of pharmacological properties. A recent study demonstrated a neuroprotective effect of SS in a mouse nerve injury model. However, its protective effects on cerebral ischemia/reperfusion injury (CIRI) remain to be elucidated. We investigated herein the in vitro and in vivo neuroprotective effects of SS. Primary hippocampal neurons were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to construct an in vitro model while rats were treated with middle cerebral artery occlusion/reperfusion (MCAO/R) to establish an in vivo CIRI model. The results showed that SS reduced OGD/R-induced inflammatory responses of neurons by blocking secretion of TNF & alpha;, IL-1 & beta; and IL-6. Moreover, SS ameliorated OGD/R-induced oxidative stress in neurons by decreasing the level of ROS and MDA and increasing the activity of SOD and GPx. We also found that SS protected neurons from OGD/Rinduced apoptosis by down-regulating bax and cleaved caspase-3 and up-regulating bcl-2. The in vivo results revealed that SS administration reduced the infarct volume and alleviated the neurological deficit of MCAO/R rats as well as diminished neuronal damages in these rats. Our investigation on the underlying mechanisms indicated that the neuroprotective effect of SS on CIRI may be associated with the TLR4/MyD88/NF-& kappa;B and AMPK/Nrf2/HO-1 pathways. Taken together, these findings demonstrate that SS ameliorates CIRI via suppressing TLR4/MyD88/NF-& kappa;B pathway and activating AMPK/Nrf2/HO-1 pathway.

Automated summary

Solasonine exhibits neuroprotective effects on cerebral ischemia/reperfusion injury by reducing inflammatory responses, oxidative stress, and neuronal apoptosis, and improving neurological function and neuronal damage.