Objective: To investigate protective effects of Spilanthes acmella(S,acmella) Murr,extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic(SH-SY5Y) cells lines,Methods: Cell viability of SH-SY5 Y cells was studied by treating the cells with various concentration of pirimicarb for 24 hr,Neuroprotective effect of S,acmella Murr,extracts was investigated by adding the plant extracts to the medium for 24 hr prior to the incubation with 100 μM H_2O_2 or with pirimicarb for 24 hr,Control-untreated cells were incubated with the culture medium,Cell viability was measured by MTT assay,calpain and calpastatin expressions were analyzed by Western blotting and immunocytochemistry,Results: Pretreatment of SH-SY5 Y cells with S,acmella Murr,extracts(1 μg/m L) for 24 hr significantly increased the dopaminergic neurons in pirimicarb-induced neurotoxicity,In addition,pretreatment with the S,acmella Murr,extracts led to decreased calpain but increased calpastatin protein levels,Conclusion: S,acmella Murr,extracts exerted neuroprotective effect,via an alteration of calcium homeostasis,against pirimicarb induced neurotoxicity,The S,acmella Murr,might be a potential natural candidate with neuroprotective activity. Objective: To investigate protective effects of Spilanthes acmella (S, acmella) Murr, extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic (SH-SY5Y) cells lines, Methods: Cell viability of SH- SY5 Y cells was studied by treating the cells with various concentrations of pirimicarb for 24 hr, Neuroprotective effect of S, acmella Murr, extracts was investigated by adding the plant extracts to the medium for 24 hr prior to the incubation with 100 μM H_2O_2 or with pirimicarb for 24 hr, Control-untreated cells were incubated with the culture medium, Cell viability was measured by MTT assay, calpain and calpastatin expressions analyzed by Western blotting and immunocytochemistry, Results: Pretreatment of SH-SY5 Y cells with S, acmella Murr, extracts (1 μg / mL) for 24 hr significantly increased the dopaminergic neurons in pirimicarb-induced neurotoxicity, In addition, pretreatment with the S, acmella Murr, extracts led to decreased calp ain but increased calpastatin protein levels, Conclusion: S, acmella Murr, extracts exerted neuroprotective effect, via an alteration of calcium homeostasis, against pirimicarb induced neurotoxicity, The S, acmella Murr, might be a potential natural candidate with neuroprotective activity.