Tetrandrine mediates autophagy via sirtuin 3/adenosine 5-monophosphate-activated protein kinase/mammalian target of rapamycin signal pathway to attenuate early brain injury after subarachnoid hemorrhage

ObjectiveEarly brain injury (EBI) is the main cause of poor outcomes in patients with subarachnoid hemorrhage (SAH). Tetrandrine (Tet) is the root of Stephania tetrandra S Moore extract that has been shown to promote neuronal survival and regulate a variety of signaling pathways; however, the mechanism through which it exerts neuroprotective effects in patients with SAH is unknown. This investigation was to examine Tet's effect on EBI in SAH rats.Basic MethodsWe divided the rats into four groups. The effects of Tet treatment on the pathological changes of neurons in rat brains were evaluated, as well as autophagy-related and signaling pathway proteins.Main ResultsWe found that Tet had a neuroprotective effect on EBI after SAH, as evidenced by the fact that Tet ameliorated SAH-mediated neurologic impairment and neuronal morphological damage and reduced brain water content, neuronal apoptosis rate, and neuronal cell loss. Tet decreased the LC3II/LC3I ratio, elevated P62 protein expression, and inhibited autophagosome production after SAH. Tet may have increased sirtuin 3 (SIRT3) expression, decreased adenosine 5-monophosphate-activated protein kinase (AMPK) phosphorylation, and increased phosphor-mammalian target of rapamycin (mTOR) levels, all of which may have occurred particularly via SIRT3/AMPK/mTOR signaling pathway activation; However, this trend can be reversed by 3-(1H-1,2,3-triazol-4-yl) pyridine (SIRT3 inhibitors).ConclusionsTet exerts neuroprotective effects by inhibiting autophagy, this may be associated with SIRT3's inhibitory effect on the AMPK/mTOR signaling pathway. This inhibition could function as a potential mechanism for the neuroprotective effects observed in patients suffering from SAH.