Protective Efficacy of Spilanthes acmella Murr. Extracts and Bioactive Constituents in Neuronal Cell Death

Spilanthes acmella Murr., a well-known Thai traditional medicine, has been used for treatment of toothache, rheumatism, and fever. Diverse pharmacological activities of S. acmella Murr. have been reported. In this study, antioxidative and neuroprotective effects of S. acmella Murr. extracts as well as bioactive scopoletin, vanillic acid, and trans-ferulic acid found in the aerial parts of this plant species have been described. Protective effect of S. acmella Murr. extracts and bioactive compounds on dexamethasone-induced neuronal cell death was investigated. Different plant crude ethyl acetate (EtOAc) and methanol (MeOH) extracts including pure compounds of S. acmella Murr. were evaluated in human neuroblastoma SH-SY5Y cells. Cytotoxic effects were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanisms involved in the antioxidant effects of S. acmella Murr. regarding the activation of antioxidant marker proteins such as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) were determined using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, Western blot analysis, and immunocytochemistry. Dexamethasone significantly caused the decrease of SH-SY5Y cell viability. Conversely, the increases in reactive oxygen species (ROS), autophagy, and apoptosis were observed in dexamethasone-treated cells. S. acmella Murr. MeOH and EtOAc extracts, as well as the bioactive compounds, reversed the toxic effect of dexamethasone by increasing the cell viability, SIRT3 protein expression but reducing the ROS, autophagy, and apoptosis. This study demonstrated that S. acmella Murr. may exert its protective effects against ROS through SOD2 and SIRT3 signaling pathways in dexamethasone-induced neurotoxicity. S. acmella Murr. may be a candidate therapy for neuroprotection.