Sinapic Acid Protects SH-SY5Y Human Neuroblastoma Cells against 6-Hydroxydopamine-Induced Neurotoxicity

Abstract

Parkinson’s disease (PD) is characterized by progressive dopaminergic neuron loss or dysfunction and is the second most prevalent neurodegenerative disorder after Alzheimer’s disease. However, current therapeutic strategies for PD are limited to treating the outcomes of this disease rather than preventing it. Sinapic acid (SA) is a phenolic compound with potential antioxidant properties, which reportedly acts as a therapeutic agent against many diseases including cancer, as well as cardiac and liver diseases. However, little is known about the effects of SA against neurodegenerative disorders. Therefore, our study sought to evaluate the neuroprotective effects of non-cytotoxic concentrations of SA against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y human neuroblastoma cells, which we used as an in vitro PD model. SA increased cell viability and rescued the cells from 6-OHDA-induced apoptotic cell death. Additionally, oxidative stress responses were significantly blocked by SA, including reactive oxygen species (ROS) overproduction and decreased expression levels of antioxidant proteins. Notably, SA also attenuated mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Moreover, SA dramatically inhibited the activation of mitogen-activated protein kinase (MAPK) proteins. Taken together, our findings highlight the potential PD prevention effects of SA, as well as its underlying mechanisms, making this compound a promising prevention and treatment agent for PD.

Mechanisms involved in the anticancer effects of sinapic acid

“…Similarly, the mRNA expression of CASP3 was increased to 1.53-fold; CASP8 to 1.77-fold; CASP9 to 1.21-fold; BAX to 1.47-fold and FAS to 1.39-fold. Other studies have also reported the apoptosis-inducing nature of SA in neuroblastoma (Tungalag and Yang 2021), breast cancer (Kampa et al 2004) and oral cancer (Kalaimathi and Suresh 2015b).…”

“…Another study also reported the ability of SA to improve cellular antioxidants against lung cancer (Hu et al 2021). Tungalag et al (2021) showed that the expression of antioxidant proteins such as SOD1, SOD2 and CAT were significantly increased upon SA treatment in SH-SY5Y human neuroblastoma cells. Other than its potent antioxidant function, SA also possesses pro-oxidant effect that has been identified to affect the redox state of tumor cells (Martin-Cordero et al 2012).…”

Chemical Constituents and Neuroprotective Activity of Hypericum hookerianum

“…The neurotoxin 6-OHDA has a similar structure to dopamine and is widely used to selectively damage dopaminergic neurons in vitro and in vivo. 37,38 Once in neurons, 6-OHDA accumulates and undergoes non-enzymatic auto-oxidation promoting the formation of ROS. The SH-SY5Y is a dopaminergic neuronal cell line of human neuroblastoma and it has been utilized in in vitro assays to determine the effect of protective and therapeutic agents for Parkinson's disease.…”

Sinapis Semen: A review on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics

“…Sinapic acid (2) in SS can increase cell viability and protect cells from 6-OHDA-induced apoptotic cell death. It significantly blocks Frontiers in Pharmacology frontiersin.org oxidative stress, including excessive production of reactive oxygen species (ROS) and decrease in the expression level of antioxidant proteins, and it also reduces mitochondrial dysfunction and endoplasmic reticulum (ER) stress, and observably inhibits mitogen-activated protein kinase (MAPK) protein activation (Zare et al, 2015;Tungalag and Yang, 2021), thereby preventing neurodegenerative diseases. Sinapic acid (2) also promotes CREB mRNA transcription in cells, activates the cAMP/PKA/CREB signaling pathway, improves Aβ1-42-induced PC12 cell morphology, and reduces Aβ42 content in cells (Xue et al, 2021;Xue et al, 2022).…”