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.

Abstract

Objective: Early 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 methods: We 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 results: We 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).

Conclusions: Tet 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.