Context: A new caffeic acid derivative, named (7'Z)-3-O-(3, 4-dihydroxyphenylethenyl)-caffeic acid (CADP), extracted from Abacopteris penangiana (Hook.) Ching. Objective: To elucidate the neuroprotective effect of CADP against H2O2-induced cytotoxicity in PC12 cells and D-galactose (D-gal)-induced neurotoxicity in mice brain. Materials and methods: CADP was isolated from the methanol extract of the rhizomes of A. penangiana. In vitro, the protective effect of CADP (0.1-10 mu M) against H2O2-induced oxidative damage on PC12 cells was investigated by a MTT assay. In vivo, behavioral tests and antioxidant enzymes measurements were performed to investigate the protective effect of intraperitoneal (i.p.) injection of CADP (5 or 10 mg/kg/day) for 2 weeks on D-gal-induced neurotoxicity in mice. Results: The results showed that CADP significantly attenuated cell toxicity in a dose-dependent manner, and the EC50 value of CADP was 0.83 +/- 0.02 mu M. In vivo, it was found that CADP significantly improved the behavioral performance of D-gal-treated mice in both Morris water maze (MWM) test and step-down avoidance test. As compared with model group, CADP (5, 10 mg/kg/day) attenuated the decrease in superoxide dismutase (SOD) activities by 40.5 and 75.4%, respectively; attenuated the decrease in glutathione peroxidase (GPx) activities by 53.8 and 73.2%, respectively; attenuated the decrease in catalase activities by 12.0 and 53.3%, respectively; reduced the increased levels of malondialdehyde (MDA) by 38.6 and 79.9%, respectively. Discussion and conclusion: The results suggested that CADP has significant neuroprotective effects which can be attributed to inhibiting the generation of free radical and enhancing the activity of endogenous antioxidant enzymes.