BACKGROUND: Sodium ferulate (SF) has an effect of anti-inflammation; however, whether it can inhibit beta-amyloid (Aβ) induced damage or not should be further studied. OBJECTIVE: To investigate the effects of SF on neurotoxicity mediated by Aβ-induced macrophage activation via inhibiting tumor necrosis factor-α (TNF-α) in vitro. DESIGN: A contrast experiment based on cells. SETTING: Departments of Pathophysiology, Pharmacology and Anatomy, Liaoning Medical College. MATERIALS: A total of 36 Kunming mice aged 8-10 weeks and some SD rats aged 2-3 days of both genders were selected in this study. Main reagents were detailed as follows: Aβ peptide (Sigma Company); SF (purity > 99%, Suzhou Changtong Chemical Co., Ltd.); lactate dehydrogenase (LDH) assay kit (Bangding Biological Engineering Co., Beijing, China); microtubule-associated protein 2 (MAP-2) monoclonal antibodies and TNF-α monoclonal antibodies (Boster Biological Engineering Co., Wuhan, China). METHODS: The experiment was carried out in Laboratories of Pharmacology and Anatomy, Liaoning Medical College from May to December 2004. Cerebellum was obtained from rats under sterile condition to culture neurons and macrophages taken from mice abdominal cavity. Later, two parallel experiments were performed as follows: ① Macrophages culture groups: In normal control group, macrophages were cultured in DMEM after being seeded. In Aβ group, neurotoxic form of Aβ was added into DMEM media with final concentration of 10 μmol/L after macrophages were seeded for 24 hours. In Aβ+SF group, ten minutes after Aβ treatment, for 10, 100, 500 μmol/L and 1 mmol/L of SF were added to the media of the macrophages culture. ② Macrophages-neurons co-cultured groups: Control macrophages-neurons were co-cultured. Aβ group: Neurotoxic form of Aβ was added into the media with concentration of 10 μmol/L after macrophages were seeded in the neurons cultured wells for 24 hours. Aβ+SF group: Ten minutes after Aβ treatment, 10, 100, 500 μmol/L and 1 mmol/L of SF were added. MAP-2 expression was detected by immunocytochemical technique and the level of LDH in the medium was measured. Data were compared with t test. MAIN OUTCOME MEASURES: Differences of concentration of TNF-α secreted from cultured macrophages, difference of amount of released LDH from neurons in co-cultured and difference of expression of MAP-2 in all co-cultured neurons. RESULTS: A total of 36 mice and 100 rats were involved in the final analysis. ① Concentration of TNF-α secreted from cultured macrophages: Amount of TNF-α was higher in Aβ group than normal control group [(282±15), (18±5) ng /L, t=-38.5, P < 0.01]. When SF (10, 100, 500 μmol/L and 1 mmol/L) was added in, secreted TNF-α was decreased in a dose-dependent manner [(238±6), (187±7), (118±8), (72±11) ng/L], and all were lower than that in Aβ group (t =10.9-40.5, P < 0.01); moreover, there were significant differences in various concentrations (F=8.56, P< 0.05). ② Amount of released LDH and expression of MAP-2: Compared with control group, the amount of Aβ-induced LDH released from neurons in Aβ group raised significantly [(285 9±250), (375±58) nkat/L, t =-24.2, P < 0.01], which indicated damage of neurons. SF (10, 100, 500 μmol/L and 1 mmol/L) suppressed the Aβ-induced LDH production from co-cultured neurons in a dose-dependent manner (t=4.2-25.2, P < 0.01). Numbers of positive cells of MAP-2 were less in Aβ group than normal control group (t =14.7, P < 0.01). With the increase of concentration of SF, numbers of positive cells of MAP-2 increased, which were obviously more than those in Aβ group (t=-9.7 to -121.0, P < 0.01). There were significant differences between numbers of positive cells of MAP-2 and LDH released amount in various concentrations of SF (F=8.56, 7.46, P < 0.05). CONCLUSION: ① Aβ activates macrophages to secrete TNF-α so as to result in neurons damage. ② SF can inhibit excretion of TNF-α, decrease Aβ-induced released LDH and reduce MAP-2 expression, so as to play a key role in protecting the neurons against the Aβ impairments. The effect is characterized by dosage dependence. BACKGROUND OF THE INVENTION: Sodium ferulate (SF) has an effect of anti-inflammation; however, whether it can inhibit beta-amyloid (Aβ) induced damage or not be further studied. OBJECTIVE: To investigate the effects of SF on neurotoxicity mediated by Aβ- induced macrophage activation via inhibiting tumor necrosis factor-α (TNF-α) in vitro. DESIGN: A contrast experiment based on cells. SETTING: Departments of Pathophysiology, Pharmacology and Anatomy, Liaoning Medical College. MATERIALS: A total of 36 Kunming mice aged 8-10 weeks and some SD rats aged 2-3 days of both genders were selected in this study. Main reagents were detailed as follows: Aβ peptide (Sigma Company); SF (purity> 99%, Suzhou Changtong Chemical Co., Ltd ); lactate dehydrogenase (LDH) assay kit (Bangding Biological Engineering Co., Beijing, China); microtubule-associated protein 2 (MAP- METHODS: The experiment was car ried out in Laboratories of Pharmacology and Anatomy, Liaoning Medical College from May to December 2004. Cerebellum was obtained from rats under sterile condition to culture neurons and macrophages taken from mice abdominal cavity. Later, two parallel experiments were performed as follows: ① Macrophages culture groups: In normal control group, macrophages were cultured in DMEM after being seeded. In Aβ group, neurotoxic form of Aβ was added into DMEM media with final concentration of 10 μmol / L after macrophages were seeded for 24 hours. In Aβ + SF group , ten minutes after Aβ treatment, for 10, 100, 500 μmol / L and 1 mmol / L of SF were added to the media of the macrophages culture. ② Macrophages-neurons co-cultured groups: Control macrophages-neurons were co-cultured Aβ group: Neurotoxic form of Aβ was added into the media with concentration of 10 μmol / L after macrophages were seeded in the neurons cultured wells for 24 hours. Aβ + SF group: Ten minutes after Aβ treatment, 10 , 100, 500 μmol / L andMAP-2 expression was detected by immunocytochemical technique and the level of LDH in the medium was measured. Data were compared with t test. MAIN OUTCOME MEASURES: Differences of concentration of TNF-α secreted from cultured macrophages, difference of amount of released LDH from neurons in co-cultured and difference of expression of MAP-2 in all co-cultured neurons. RESULTS: A total of 36 mice and 100 rats were involved in the final analysis. ① Concentration of TNF -α secreted from cultured macrophages: Amount of TNF-α was higher in Aβ group than normal control group [(282 ± 15), (18 ± 5) ng / L, t = -38.5, P <0.01] 10, 100, 500 μmol / L and 1 mmol / L) was added in a dose-dependent manner [(238 ± 6), (187 ± 7), (118 ± 8), 72 ± 11) ng / L], and all were lower than that in Aβ group (t = 10.9-40.5, P <0.01); moreover, there were significant differences in various concentrations Amount of released LD H and expression of MAP-2: Compared with control group, the amount of Aβ-induced LDH released from neurons in Aβ group was significantly increased (285 9 ± 250), (375 ± 58) nkat / L, t = -24.2, P <0.01], which indicated the damage of neurons. SF (10, 100, 500 μmol / L and 1 mmol / L) suppressed the Aβ-induced LDH production from co- cultured neurons in a dose- 25.2, P <0.01). The numbers of positive cells of MAP-2 were less in Aβ group than normal control group (t = 14.7, P <0.01) increased, which were significantly more than those in Aβ group (t = -9.7 to -121.0, P <0.01). There were significant differences between numbers of positive cells of MAP-2 and LDH released amount in various concentrations of SF (F = 8.56, 7.46, P <0.05). CONCLUSION: ① Aβ activates macrophages to secrete TNF-α so as to result in neurons damage. ② SF can inhibit excretion of TNF-α, decrease Aβ-induced released LDH and reduce MAP-2 expression, so as to playa key role in protecting the neurons against the Aβ impairments. The effect is characterized by dosage dependence.