Tanshinone IIA protects PC12 cells from β-amyloid25–35-induced apoptosis via PI3K/Akt signaling pathway

Abstract

For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer’s dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid β peptides (Aβ)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with β-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Aβ(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3β, which is a downstream target of PI3K/Akt, can block Aβ(25-35)-induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3β phosphorylation are involved in the neuroprotection of Tan IIA.

Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494

“…Accumulating evidence has proved that PI3K/AKT/mTOR and MAPK signaling pathways are closely related to cell proliferation and apoptosis [ 33 , 34 ]. PC12 cell apoptosis, induced by sodium nitroprusside or β-amyloid, has been reported to be repressed through PI3K/AKT/mTOR pathway [ 35 , 36 ]. Likewise, cell apoptosis of PC12 cells could be suppressed by nobiletin [ 37 ] or gastrodin [ 38 ] through MAPK signaling pathway.…”

Tanshinone IIA Inhibits Glutamate‐Induced Oxidative Toxicity through Prevention of Mitochondrial Dysfunction and Suppression of MAPK Activation in SH‐SY5Y Human Neuroblastoma Cells

“…However, further investigation is needed to unravel the signaling mechanisms of tanshinone IIA against glutamate neurotoxicity as other pathways may also be involved in the neuroprotective effect of tanshinone IIA. For example, tanshinone IIA is shown to protect PC12 cells against amyloid β -protein-induced apoptosis via the PI3K/Akt signaling pathway, an important survival mechanism which is also implicated in glutamate excitotoxicity [12, 61]. …”

Tanshinone IIA attenuates Aβ25–35-induced spatial memory impairment via upregulating receptors for activated C kinase1 and inhibiting autophagy in hippocampus

“…Tanshinone IIA (Tan IIA) is one of the main active ingredients extracted from the rhizome of the Salvia miltiorrhiza . Recent studies have elucidated the neuroprotective action and molecular mechanism of Tan IIA in vitro and in vivo, including AD . Recently, some reports have indicated that Tan IIA dramatically activated the ERK signalling pathway and induced autophagic cell death .…”

“…Tanshinone IIA has been extensively used in the treatment of cardiovascular disease and cerebrovascular disease . Additionally, Tanshinone IIA has been suggested efficacious in preventing memory deficits by ameliorating neuronal damage and protecting against Aβ 25–35 ‐induced neurotoxicity and the pathological features of AD . Of interest, a recent study demonstrated that Tanshinone IIA could markedly induce autophagic cell death in KBM‐5 leukaemia cells .…”