Tanshinone IIA attenuates Aβ-induced neurotoxicity by down-regulating COX-2 expression and PGE2 synthesis via inactivation of NF-κB pathway in SH-SY5Y cells

Abstract

Amyloid-β (Aβ)-induced neurotoxicity is a major pathological mechanism of Alzheimer’s disease (AD). Tanshinone IIA (Tan IIA), extracted from traditional Chinese herb Radix salvia miltiorrhiza, possesses anti-oxidant and anti-inflammatory actions, as well as neuroprotective effects. The present study aims to explore the possible mechanism by which Tan IIA attenuated Aβ-induced neurotoxicity. Exposure of SH-SY5Y cells to different concentrations of Aβ led to neurotoxicity by reducing cell viability, inducing cell apoptosis and increasing neuroinflammation in a dose-dependent manner. Moreover, Aβ treatment promoted cyclooxygenase-2 (COX-2) expression and Prostaglandin E2 (PGE2) secretion, and activated nuclear transcription factor kappa (NF-κB) pathway in SH-SY5Y cells. However, pretreatment of SH-SY5Y cells with Tan IIA prior to Aβ prevented these Aβ-induced cellular events noticeably. These data suggested that Tan IIA exerted its neuroprotective action by alleviating Aβ-induced increase in COX-2 expression and PGE2 secretion via inactivation of NF-κB pathway.

RETRACTED: Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway

“…Therefore, COX-2 inhibition could be useful for the treatment of esophageal cancer. Tan IIA could downregulate COX-2 expression and inactivate the NF-κB pathway in SH-SY5Y cells (39).…”

“…COX-2 has been shown to be a key molecular regulator of cancer progression and metastasis and a crucial target in cancer therapy. A recent study found that tan IIA could downregulate COX-2 expression and inactivate the NF-κB pathway in SH-SY5Y cells ( 39 ). Therefore, we used molecular docking for further research.…”

“…A recent study found that tan IIA could downregulate COX-2 expression and inactivate the NF-κB pathway in SH-SY5Y cells (39). Therefore, we used molecular docking for further research.…”

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

“…Furthermore, it inhibited the expression at the transcriptional and translational levels of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) and nuclear transcription factor κ (NF-κBp65) genes. Improvements in memory, reduction in AChE activity, mitigation of neuronal damage and oxidative stress, and in restoring cholinergic balance have also been observed in other studies following administration of this compound [427,428].…”

The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation

“…Tanshinone IIA, a lipophilic diterpene found in the Chinese traditional herb, Danshen, exhibits antioxidant, anti-inflammatory, antitumor, cardiovascular-protective, and neuroprotective effects. Tanshinone IIA reduced the production of pro-inflammatory mediators by inhibiting the NF-κB pathway, promoted the shift from M1 microglia to M2 microglia, and activated macrophage migration inhibitory factor (MIF), thereby attenuating neuroinflammation [ 108 , 109 , 110 ].…”